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Evidence Summary

Other Supporting Document for Prostate Cancer: Screening

Preface

A Review of the Evidence for the U.S. Preventive Services Task Force

Release Date: October 2011


By Roger Chou, MD; Jennifer M. Croswell, MD, MPH; Tracy Dana, MLS; Christina Bougatsos, BS; Ian Blazina, MPH; Rongwei Fu, PhD; Ken Gleitsmann, MD, MPH; Helen C. Koenig, MD, MPH; Clarence Lam, MD, MPH; Ashley Maltz, MD, MPH; J. Bruin Rugge, MD, MPH; and Kenneth Lin, MD


The information in this article is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This article is intended as a reference and not as a substitute for clinical judgment.

This article may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

This article was first published in Annals of Internal Medicine on October 7, 2011 (www.annals.org).

Abstract

Background: Screening can detect prostate cancer at earlier, asymptomatic stages, when treatments might be more effective.

Purpose: To update the 2002 and 2008 U.S. Preventive Services Task Force evidence reviews on screening and treatments for prostate cancer.

Data Sources: MEDLINE (2002 to July 2011) and the Cochrane Library Database (through second quarter of 2011).

Study Selection: Randomized trials of prostate-specific antigen–based screening, randomized trials and cohort studies of prostatectomy or radiation therapy versus watchful waiting, and large observational studies of perioperative harms.

Data Extraction: Investigators abstracted and checked study details and quality using predefined criteria.

Data Synthesis: Of 5 screening trials, the 2 largest and highest-quality studies reported conflicting results. One found that screening was associated with reduced prostate cancer–specific mortality compared with no screening in a subgroup of men aged 55 to 69 years after 9 years (relative risk, 0.80 [95% CI, 0.65 to 0.98]; absolute risk reduction, 0.07 percentage point). The other found no statistically significant effect after 10 years (relative risk, 1.1 [CI, 0.80 to 1.5]). After 3 or 4 screening rounds, 12% to 13% of screened men had false-positive results. Serious infections or urinary retention occurred after 0.5% to 1.0% of prostate biopsies. There were 3 randomized trials and 23 cohort studies of treatments. One good-quality trial found that prostatectomy for localized prostate cancer decreased risk for prostate cancer–specific mortality compared with watchful waiting through 13 years of follow-up (relative risk, 0.62 [CI, 0.44 to 0.87]; absolute risk reduction, 6.1%). Benefits seemed to be limited to men younger than 65 years. Treating approximately 3 men with prostatectomy or 7 men with radiation therapy instead of watchful waiting would each result in 1 additional case of erectile dysfunction. Treating approximately 5 men with prostatectomy would result in 1 additional case of urinary incontinence. Prostatectomy was associated with perioperative death (about 0.5%) and cardiovascular events (0.6% to 3%), and radiation therapy was associated with bowel dysfunction.

Limitation: Only English-language articles were included. Few studies evaluated newer therapies.

Conclusion: Prostate-specific antigen–based screening results in small or no reduction in prostate cancer–specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary.

Primary Funding Source: Agency for Healthcare Research and Quality

Introduction

Prostate cancer is the most commonly diagnosed cancer in U.S. men 1-3. Prostate-specific antigen (PSA)–based screening can detect prostate cancers at earlier, asymptomatic stages, when treatments might be more effective.

The U.S. Preventive Services Task Force (USPSTF) last reviewed the evidence on prostate cancer screening 4 and issued recommendations in 2008 5. Since then, large trials of prostate cancer screening have been published 6, 7. Benefits and harms of treatments for prostate cancer were last reviewed by the USPSTF in 2002 8. This article summarizes 2 recent reviews commissioned by the USPSTF to synthesize the current evidence on screening 9 and treatments 10 for localized prostate cancer.

Methods

Scope of the Review

We followed a standardized protocol and developed an analytic framework that focused on the following key questions:

  1. Does PSA-based screening decrease prostate cancer–specific or all-cause mortality?
  2. What are the harms of PSA-based screening for prostate cancer?
  3. What are the benefits of treatment of early-stage or screening-detected prostate cancer?
  4. What are the harms of treatment of early-stage or screening-detected prostate cancer?

Detailed methods and data for the review, including search strategies, multiple evidence tables with quality ratings of individual studies, and pooled analyses of some harms data, are available in the full report 10. Also of note, androgen deprivation therapy, cryotherapy, and high-intensity focused ultrasonography are reviewed in the full report 10 but are not presented in this article.

Data Sources and Searches

We searched OVID MEDLINE from 2002 to July 2011, PubMed from 2007 to July 2011, and the Cochrane Library Database through the second quarter of 2011 and reviewed reference lists to identify relevant articles published in English.

Study Selection

At least 2 reviewers independently evaluated each study to determine inclusion eligibility. We restricted inclusion to published studies. We included randomized trials of screening for prostate cancer in asymptomatic men (including those with chronic, mild lower urinary tract symptoms) that incorporated 1 or more PSA measurements, with or without additional methods, such as digital rectal examination, and reported all-cause or prostate cancer–specific mortality or harms associated with screening. We also included randomized trials and cohort studies of men with screening-detected prostate cancer that compared radical prostatectomy or radiation therapy (the most common primary treatments for localized prostate cancer 11, 12 with watchful waiting and reported all-cause mortality, prostate cancer–specific mortality, or prespecified harms (quality of life or functional status, urinary incontinence, bowel dysfunction, erectile dysfunction, psychological effects, and surgical complications). We included studies of clinically localized (T1 or T2) prostate cancer because more than 90% of screening-detected prostate cancers are localized 6, 7, 13. We included only studies that reported risk estimates for mortality adjusted at a minimum for age at diagnosis and tumor grade (no study reported adjusted risk estimates for treatment harms). We also included large (>1000 participants) uncontrolled observational studies of perioperative mortality and surgical complications.

We classified “no treatment,” “observation,” or “deferred treatment” as watchful waiting because patients probably received at least watchful waiting. We also grouped watchful waiting with active surveillance because studies of active surveillance provided insufficient information to determine whether more active follow-up actually occurred 14, and older studies used these terms interchangeably.

Data Extraction and Quality Assessment

One investigator abstracted details about the patient population, study design, analysis, duration of follow-up, and results. A second investigator reviewed data abstraction for accuracy. Two investigators independently applied criteria developed by the USPSTF 15 to rate the quality of each study as good, fair, or poor. Discrepancies were resolved through a consensus process.

Data Synthesis and Analysis

We assessed the aggregate internal validity (quality) of the body of evidence for each key question (good, fair, and poor) by using methods developed by the USPSTF on the basis of the number, quality, and size of studies; consistency of results between studies; and directness of evidence 15. We synthesized results of treatment studies descriptively, using medians and ranges, because few randomized, controlled trials (RCTs) were available and studies varied in the populations and interventions evaluated, methodologic quality, duration of follow-up, and other factors. We stratified results according to study type and qualitatively assessed the effects of study quality, duration of follow-up, year of publication, and mean age on results.

Role of the Funding Source

This study was funded by the Agency for Healthcare Research and Quality (AHRQ) under a contract to support the work of the USPSTF. Staff at AHRQ and USPSTF members helped develop the scope of this work and reviewed draft manuscripts. The draft systematic reviews were reviewed by external peer reviewers not affiliated with the USPSTF, then revised for the final version. Approval from AHRQ was required before this manuscript could be submitted for publication, but the authors are solely responsible for the content and the decision to submit.

Results

Appendix Figure 1 and Appendix Figure 2 show the results of the search and study selection process.

We identified 2 fair-quality 6, 7 and 3 poor-quality 16-20 randomized trials of PSA-based screening (Appendix Table 1). We also included a report describing results from a single center 21 participating in a fair-quality trial 7. Sample sizes ranged from 9026 to 182,160 and maximum follow-up from 11 to 20 years (median, 6 to 14 years).

We identified 11 studies (2 RCTs 22-29 and 9 cohort studies 30-38) on benefits of prostate cancer treatments and 16 studies (2 RCTs 39-42 and 14 cohort studies 43-58) on harms (Appendix Table 2). Sample sizes ranged from 72 to 44,630 and duration of follow-up from 1 to 23 years. Four studies were rated good quality 23, 42, 52, 56, 58, 1 poor quality 29, and the remainder fair quality. Frequent methodologic shortcomings were failure to describe loss to follow-up (6 cohort studies and all 3 RCTs met this criterion) and inadequate blinding of outcome assessors (no cohort studies and 1 RCT met this criterion). Only 2 studies 33, 40 clearly described the control group intervention (Appendix Table 2). We also included 6 observational studies 59-64 of surgical complications after prostatectomy.

Key Question 1: Does PSA-Based Screening Decrease Prostate Cancer–Specific or All-Cause Mortality?

The fair-quality U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial randomly assigned 76,693 men between 55 and 74 years of age to annual PSA screening in combination with digital rectal examination versus usual care 6. After 7 years' (complete) follow-up, screening was associated with increased prostate cancer incidence (relative risk [RR], 1.2 [95% CI, 1.2 to 1.3]) but no effect on prostate cancer–specific (RR, 1.1 [CI, 0.75 to 1.7]) or all-cause (RR, 0.98 [CI, 0.92 to 1.0]) mortality. Similar results were observed after 10 years (67% of sample; RR, 1.1 [CI, 0.80 to 1.5]). Up to 52% of men assigned to usual care underwent a PSA test at some point during the trial, and 44% of trial participants had undergone PSA screening before entry.

The fair-quality European Randomized Study of Screening for Prostate Cancer (ERSPC) randomly assigned 182,000 men aged 50 to 74 years from 7 countries to PSA testing every 2 to 7 years (depending on center and year) or to usual care 7. Data from 2 other study centers were excluded for reasons not specified in the study protocol. Levels of PSA for diagnostic evaluation ranged from 2.5 to 4.0 µg/L (1 center used 10 µg/L for several years). Recruitment and randomization procedures and age eligibility also varied. After a median of 9 years, prostate cancer incidence was higher in the screened group (net increase, 34 per 1000 men), but there was no statistically significant difference in prostate cancer–specific mortality (RR, 0.85 [CI, 0.73 to 1.0]). A prespecified subgroup analysis of 162,243 men aged 55 to 69 years found that screening was associated with reduced prostate cancer–specific mortality (RR, 0.80 [CI, 0.65 to 0.98]; absolute risk reduction, 0.07 percentage point), for an estimated 1410 men invited to screening and 48 treated to prevent 1 prostate cancer–specific death.

After publication of the main ERSPC results, 1 participating center (Göteborg, Sweden) reported results separately 21. It found PSA screening (threshold, 2.5 to 3.0 µg/L) every 2 years in 20,000 men aged 50 to 64 years to be associated with increased prostate cancer incidence (hazard ratio [HR], 1.6 [CI, 1.5 to 1.8]) and decreased risk for prostate cancer–specific mortality (RR, 0.56 [CI, 0.39 to 0.82]; absolute risk reduction, 0.34 percentage point) after a median of 14 years. Outcomes for 60% of participants were included in the main ERSPC report 7. Although no other center separately reported results, only exclusion of the Swedish center data from the overall ERSPC analysis resulted in loss of the statistically significant effect of screening on prostate cancer–specific mortality (RR, 0.84 [CI, 0.70 to 1.01]), suggesting better results than the other centers 7.

Three poor-quality trials (number of men invited to screening ranged from 1494 to 31,333) found no difference between screening-invited and control groups in prostate cancer–specific mortality risk 16, 17, 20. Two of the trials 17, 19 were included in the 2008 USPSTF review 4; results after 5 years' additional follow-up are now available from 1 of the trials 20. Methodological shortcomings in these trials included failure to describe adequate randomization or allocation concealment methods, poorly described loss to follow-up, and unclear masking of outcomes assessors. One trial used a high PSA cut point (10 µg/L) 16.

Key Question 2: What Are the Harms of PSA-Based Screening for Prostate Cancer?

Direct harms of PSA-based screening were reported in the ERSPC and PLCO trials 6, 7. The Finnish center of the ERSPC trial found that 12% of men received at least 1 false-positive result after 3 rounds of PSA testing (cutoff, 4.0 µg/L) 65. For the entire ERPSC trial, 76% of prostate biopsies for an elevated PSA level identified no cancer 7. In the PLCO trial, the cumulative risk for at least 1 false-positive result was 13% after 4 PSA tests (cutoff, 4.0 µg/L), with a 5.5% risk for undergoing at least 1 biopsy due to a false-positive test result 66.

Physical harms of screening in the PLCO trial included bleeding or pain from digital rectal examination (0.3 event per 10,000 screened); bruising or fainting due to venipuncture (26 events per 10,000 screened); and biopsy complications, such as infection, bleeding, and urinary difficulties (68 events per 10,000 evaluations) 6. The Rotterdam, Netherlands, center of the ERSPC trial reported that among 5802 biopsies performed, 200 men (3.5%) developed fever, 20 (0.4%) experienced urine retention, and 27 (0.5%) required hospitalization for signs of prostatitis or urosepsis 67.

None of the RCTs of PSA-based screening provided information on potential psychological harms, such as anxiety, or adverse effects on health-related quality of life. The 2008 USPSTF review found evidence that false-positive PSA test results are associated with adverse psychological effects but could not estimate their magnitude 4.

Key Question 3: What Are the Benefits of Treatment of Early-Stage or Screening-Detected Prostate Cancer?

Prostatectomy

Prostatectomy was compared with watchful waiting in 1 good-quality RCT (n=695) of men with localized (stage T1b, T1c, or T2) prostate cancer (Appendix Table 3) 22-24, 28. It did not specifically enroll men with screening-detected prostate cancer, and about 75% of cancers were palpable (stage T2). By comparison, 36% of localized cancers in the ERSPC screening trial were stage T2 7. The 2002 USPSTF review included results through 6 years of follow-up 28. Data now available through 15 years showed a sustained decrease in risk for prostate cancer–specific mortality (15% vs. 21%; RR, 0.62 [CI, 0.44 to 0.87]; absolute difference, 6.1 percentage points [CI, 0.2 to 12 percentage points]) and all-cause mortality (RR, 0.75 [CI, 0.61 to 0.92]; absolute difference, 6.6 percentage points [CI, −1.3 to 14 percentage points]) 23. In subgroup analyses, benefits were restricted to men younger than 65 years of age (RR, 0.49 [CI, 0.31 to 0.79] for prostate cancer–specific mortality; RR, 0.52 [CI, 0.37 to 0.73] for all-cause mortality). A small (n=142), poor-quality RCT found no difference between prostatectomy and no prostatectomy for localized prostate cancer on overall survival through 23 years 29. It did not report prostate cancer–specific mortality.

Eight cohort studies (median n=2264 [range, 316 to 25,900]) with a duration of follow-up ranging from 4 to 13 years consistently found prostatectomy for localized prostate cancer to be associated with decreased risk for all-cause mortality (6 studies; median adjusted HR, 0.46 [range, 0.32 to 0.67] 31, 33-37) and prostate cancer–specific mortality (5 studies; median adjusted HR, 0.32 [range, 0.25 to 0.50] 30, 33, 35, 36, 38) compared with watchful waiting (Appendix Table 3). The largest was a fair-quality, propensity-adjusted analysis of data from the U.S. Surveillance, Epidemiology, and End Results (SEER) program (n=25,900) of men 65 to 80 years of age that found decreased risk for all-cause mortality after 12 years (adjusted HR, 0.50 [CI, 0.66 to 0.72]) 37. A large (n=22,385), fair-quality Swedish cohort study also found prostatectomy to be associated with decreased risk for all-cause mortality after 4 years of follow-up, after adjustment for age, Gleason score, and PSA level (adjusted HR, 0.41 [CI, 0.36 to 0.48]) 31.

Radiation Therapy

No RCTs compared radiation therapy versus watchful waiting. Five cohort studies (median n=3441 [range, 334 to 30,857]) with follow-up ranging from 4 to 13 years consistently found that radiation therapy (external-beam radiation therapy [EBRT] or unspecified modality) for localized prostate cancer was associated with decreased risk for all-cause mortality (5 studies; median adjusted HR, 0.68 [range, 0.62 to 0.81] 31, 35-38) and prostate cancer–specific mortality (5 studies; median adjusted HR, 0.66 [range, 0.63 to 0.70]) compared with watchful waiting (Appendix Table 3) 30, 35-38. The largest study, a previously described analysis of SEER data, found radiation therapy to be associated with decreased propensity-adjusted risk for all-cause mortality (adjusted HR, 0.81 [CI, 0.78 to 0.85]) 37. A large Swedish cohort study (also described earlier) found radiation therapy to be associated with decreased risk for all-cause mortality (adjusted HR, 0.62 [CI, 0.54 to 0.71]) 31.

Key Question 4: What Are the Harms of Treatment of Early-Stage or Screening-Detected Prostate Cancer?

Prostatectomy

Urinary Incontinence and Erectile Dysfunction. Prostatectomy was associated with increased risk for urinary incontinence compared with watchful waiting in 1 RCT (RR, 2.3 [CI, 1.6 to 3.2]) 41 and 4 cohort studies (median RR, 4.0 [range, 2.0 to 11]) (Appendix Table 4) 47, 49, 53, 56. In the RCT, the absolute increase in risk for urinary incontinence with surgery was 28 percentage points (49% vs. 21%) 41. In the cohort studies, the median rate of urinary incontinence with watchful waiting was 6% (range, 3% to 10%), with prostatectomy associated with a median increase in absolute risk of 18 percentage points (range, 8 to 40 percentage points) 47, 49, 53, 56.

Prostatectomy was also associated with an increased risk for erectile dysfunction compared with watchful waiting in 1 RCT (RR, 1.8 [CI, 1.5 to 2.2]) 41 and 5 cohort studies (median RR, 1.5 [range, 1.3 to 2.1]) (Appendix Table 4) 47, 49, 53, 56. In the RCT, the absolute increase in risk for erectile dysfunction with surgery was 36 percentage points (81% vs. 45%) 41. In the cohort studies, the median rate of erectile dysfunction with watchful waiting was 52% (range, 26% to 68%), with prostatectomy associated with a median increase in absolute risk of 26 percentage points (range, 21 to 29 percentage points) 47, 49, 53, 56.

Differences in study quality, duration of follow-up, or year of publication did not seem to explain differences in estimates across studies. The studies provided few details about the specific surgical procedures evaluated, although open retropubic radical prostatectomy was the dominant procedure when most of the studies were conducted 68. One observational study stratified estimates for erectile dysfunction and urinary incontinence by use of a nerve-sparing (n=494; 68% and 9.4%, respectively) versus a non–nerve-sparing (n=476; 87% and 15%, respectively) technique 56.

Consistent with the studies reporting dichotomous outcomes, 8 cohort studies that evaluated urinary and sexual function outcomes by using continuous scales found that prostatectomy was associated with worse outcomes compared with watchful waiting (Appendix Table 4 43, 46, 48, 51, 53, 55-57).

Quality of Life. Eight studies reported generic quality of life 43, 46, 48, 50, 51, 53, 55, 56. Two studies reported very similar Short-Form 36 (SF-36) physical and mental component summary scores after prostatectomy and watchful waiting (Appendix Table 5) 43, 56. On specific SF-36 subscales, prostatectomy was associated with better physical function (6 studies; median difference, 8 points [range, 2 to 16 points]) 43, 46, 48, 51, 53, 55 and emotional role function subscale scores (7 studies; median difference, 8 points [range, −5 to 13 points]) 43, 46, 48, 50, 51, 53, 55, with small or no clear differences on other SF-36 subscales.

Surgical Complications. The largest (n=101,604) study of short-term (≤30-day) complications after prostatectomy reported a 30-day perioperative mortality rate of 0.5% in Medicare claimants 60; 3 other large observational studies reported similar findings 59, 61, 62. Advanced age and increased number of serious comorbid conditions were associated with higher perioperative mortality, although absolute rates were less than 1% even in men at higher risk. In the Medicare database study, perioperative rates of serious cardiovascular events were 3% and rates of vascular events (including pulmonary embolism and deep venous thrombosis) were 2% 60. In 2 other studies (n=1243 63 and 11,010 59), rates of cardiovascular events were 0.6% and 3% and rates of vascular events 1% and 2%, respectively. Serious rectal or ureteral injury due to surgery ranged from 0.3% to 0.6% 60, 63.

Other Harms. Five studies (reported in 6 publications) found no clear differences between prostatectomy and watchful waiting in risk for bowel dysfunction 41, 42, 46, 47, 49, 56. One RCT found no difference between prostatectomy and watchful waiting in risk for high levels of anxiety, depression, or worry after 4 years 42.

Radiation Therapy

Urinary Incontinence and Erectile Dysfunction. Radiation therapy was associated with increased risk for urinary incontinence compared with watchful waiting in 1 small RCT, but the estimate was very imprecise (RR, 8.3 [CI, 1.1 to 63]) because of small numbers of events (1 in the watchful waiting group) (Appendix Table 4) 39. There was no clear increase in risk in 4 (total n=1910) cohort studies (median RR, 1.1 [range, 0.71 to 2.0]) 47, 49, 53, 56.

Radiation therapy was associated with increased risk for erectile dysfunction compared with watchful waiting in 6 cohort studies, with similar estimates across studies (median RR, 1.3 [range, 1.1 to 1.5]) (Appendix Table 4) 47, 49, 53, 54, 56, 58. Rates of erectile dysfunction ranged from 26% to 68% (median, 50%) with watchful waiting; radiation therapy was associated with a median increase in pooled absolute risk of 14 percentage points (range, 7 to 22 percentage points).

Five of the six studies did not provide details about the type of radiation therapy (for example, EBRT vs. brachytherapy) or dosing regimen. One good-quality cohort study reported a 7.0% rate of urinary incontinence after high-dose brachytherapy (n=47), 5.4% after low-dose brachytherapy (n=58), and 2.7% after EBRT (n=123) 56. Rates of erectile dysfunction were 72%, 36%, and 68%, respectively.

Consistent with the studies reporting dichotomous outcomes, 10 studies found radiation therapy to be associated with worse sexual function compared with watchful waiting on the basis of continuous scales, although no clear differences were seen in sexual bother scores and measures of urinary function (Appendix Table 4) 40, 43, 46, 48, 51, 53, 55-58.

Quality of Life. Ten studies reported generic quality of life 40, 43, 46, 48, 50, 51, 53, 55, 56, 58. Three studies found no differences between radiation therapy and watchful waiting in SF-36 physical (median difference, 0 points [range, −3 to 0 points]) or mental (median difference, 0 points [range, −2 to 1 point]) component summary scores (Appendix Table 4) 43, 56, 58. Results favored watchful waiting on the physical role function subscale (7 studies; median difference, −9 points [range, −22 to 1 point]) 43, 46, 48, 51, 53, 55, 58, with no clear differences on other SF-36 subscales.

Other Harms. Six cohort studies consistently found radiation therapy to be associated with worse Prostate Cancer Index bowel bother (median difference, −6 points [range, −10 to −2 points]) and function (median difference, −8 points [range, −15 to −3 points]) than watchful waiting 43, 48, 51, 53, 56, 58. In studies that evaluated bowel function serially, effects seemed to be most pronounced in the first few months after radiation therapy and gradually improved 40, 46, 51, 57. This might help explain the inconsistent results among studies that reported dichotomous outcomes. Although 1 study found radiation therapy to be associated with substantially increased risk for bowel urgency after 2 years (3.2% vs. 0.4%; RR, 7.5 [CI, 1.0 to 56]) 47, 2 studies with longer duration of follow-up (5.6 49 and 3 years 56) found no increased risk.

One cohort study reported similar effects of EBRT and brachytherapy on Prostate Cancer Index bowel function and bother 43. Another study found low-dose brachytherapy to be associated with smaller effects on bowel bother (about 3-point change from baseline) compared with high-dose brachytherapy (9-point change) or EBRT (8-point change) 56.

No study reported effects of radiation therapy versus watchful waiting on anxiety or depression.

Discussion

The Table shows our summary of the evidence. Screening based on PSA identifies additional cases of prostate cancer, but most trials found no statistically significant effect on prostate cancer–specific mortality. Recent meta-analyses of randomized trials included in this review found no pooled effect of screening on prostate cancer–specific mortality 69, 70. However, the 2 largest and highest-quality trials reported conflicting results 6, 7. The ERSPC trial found PSA screening every 2 to 7 years to be associated with a 20% relative reduction in risk for death from prostate cancer in a prespecified subgroup of men aged 55 to 69 years 7, whereas the PLCO trial found no effect 6. High rates of previous PSA screening and contamination in the control group of the PLCO trial may have reduced its ability to detect benefits, although these factors do not explain the trend toward increased risk for prostate cancer–specific mortality in the screened group. The proportion of men in the PLCO trial who initially chose active surveillance or expectant management instead of curative treatment was lower than in the ERSPC trial (10% vs. 19%), and the PLCO trial evaluated a shorter screening interval (annual vs. every 2 to 7 years), suggesting that more conservative screening and treatment strategies might be more effective than more aggressive ones. Chance could also explain the apparent discrepancy between the 2 trials because the risk estimate CIs overlapped. Additional follow-up might help resolve the discrepancy, given the long lead time (10 to 15 years) that may be necessary to fully understand the effect of PSA-based screening.

Treatment studies can help inform screening decisions by providing information about potential benefits of interventions once prostate cancer is detected. However, only 1 good-quality randomized trial compared an active treatment for localized prostate cancer with watchful waiting 23. It found that prostatectomy was associated with decreased risk for all-cause and prostate cancer–specific mortality after 15 years of follow-up, although benefits seemed to be limited to younger men on the basis of subgroup analyses. Because the RCT did not enroll men specifically with screening-detected prostate cancer, its applicability to screening is uncertain. Although cohort studies consistently found prostatectomy and radiation therapy to be associated with decreased risk for all-cause and prostate cancer–specific mortality compared with watchful waiting, estimates are susceptible to residual confounding, even after statistical adjustment.

Screening is associated with potential harms, including serious infections or urine retention in about 1 of 200 men who undergo prostate biopsy as a result of an abnormal screening result. False-positive screening results occurred in 12% to 13% of men randomly assigned to PSA-based screening 65, 66, with 1 trial reporting no prostate cancers in three quarters of screening-triggered biopsies 7. Screening also is likely to result in overdiagnosis because of the detection of low-risk cancers that would not have caused morbidity or death during a man's lifetime, and overtreatment of such cancers, which exposes men to unnecessary harms 71. Over three quarters of men with localized prostate cancer (about 90% of screening-detected cancers are localized) undergo prostatectomy or radiation therapy 11, 12. On the basis of data from the ERSPC trial, the rate of overdiagnosis with screening was estimated to be as high as 50% 72, and 48 men received treatment for every prostate cancer–specific death prevented 7. Treating approximately 3 men with prostatectomy or 7 with radiation therapy instead of watchful waiting would each result in 1 additional case of erectile dysfunction, and treating approximately 5 men with prostatectomy instead of watchful waiting would result in 1 additional case of urinary incontinence. Prostatectomy and radiation therapy were not associated with worse outcomes on most measures related to general health-related quality of life compared with watchful waiting, suggesting that negative effects related to specific harms may be offset by positive effects (perhaps related to less worry about untreated prostate cancer). Prostatectomy was also associated with perioperative (30-day) mortality (about 0.5%) and cardiovascular events (0.6% to 3%), and radiation therapy was associated with bowel dysfunction.

The evidence on treatment-related harms reviewed for this report seemed to be most applicable to open retropubic radical prostatectomy and EBRT, although details of specific surgical techniques or radiation therapy techniques and dosing regimens were frequently lacking. We found little evidence with which to evaluate newer techniques for prostatectomy (including nerve-sparing approaches that use laparoscopy, either robotic-assisted or freehand) compared with watchful waiting, but found no pattern suggesting that more recent studies reported different risk estimates than older studies. Limited data suggest that low-dose brachytherapy may be associated with fewer harms than high-dose brachytherapy or EBRT 56. A potential harm of radiation therapy not addressed in this review is secondary posttreatment carcinogenic effects 73, 74.

Other treatments used for localized prostate cancer are reviewed in the full report, available on the USPSTF Web site 10. Although androgen deprivation is the next most commonly used therapy for localized prostate cancer after prostatectomy and radiation therapy 11, it is comparatively uncommon, and is not recommended as primary therapy 75, 76 because of evidence suggesting ineffectiveness 32, as well as an association with important adverse events, such as coronary heart disease, myocardial infarction, diabetes, and fractures, when given for more advanced prostate cancer 77-79.

Our study has limitations. We excluded non–English-language articles, which could result in language bias, although we identified no non–English-language studies that would have met inclusion criteria. We included cohort studies of treatments, which are more susceptible to bias and confounding than well-conducted randomized trials. However, confounding by indication may be less of an issue in studies that evaluate harms 80, and analyses stratified by study design did not suggest differential estimates. If patients are selected for a specific prostate cancer treatment in part because of a lower perceived risk for harms, the likely effect on observational studies would be to underestimate risks. For mortality outcomes, which may be more susceptible to confounding by indication, we included only studies that performed statistical adjustment. Finally, studies did not distinguish well between active surveillance and watchful waiting. Active surveillance might be associated with more harms (due to repeated biopsies or subsequent interventions) than watchful waiting, and studies with well-described active surveillance interventions that are consistent with current definitions for this therapy are needed 14.

In summary, PSA-based screening is associated with detection of more prostate cancers; small to no reduction in prostate cancer–specific mortality after about 10 years; and harms related to false-positive test results, subsequent evaluation, and therapy, including overdiagnosis and overtreatment. If screening is effective, optimal screening intervals and PSA thresholds remain uncertain. The ERSPC trial evaluated longer screening intervals (2 to 7 years) and in some centers lower PSA thresholds (2.5 to 4.0 µg/L) as compared with typical U.S. practice 7. When available, results from the Prostate Cancer Intervention Versus Observation Trial, which compared prostatectomy with watchful waiting for screening-detected cancer, may help clarify which patients would benefit from prostatectomy or other active treatments, potentially reducing harms from unnecessary treatment 81.

Copyright and Source Information

Source: This article was first published in Annals of Internal Medicine (Ann Intern Med 2011 Oct 7. [Epub ahead of print]).

Acknowledgment: The authors thank Mary Barton, MD, MPP, Ned Calonge, MD, MPH, and U.S. Preventive Services Task Force Leads Michael LeFevre, MD, MSPH, Rosanne Leipzig, MD, PhD, and Timothy Wilt, MD, MPH, for their contributions to this report.

Grant Support: By the Agency for Healthcare Research and Quality (contract number HHSA-290-2007-10057-I-EPC3, Task Order No. 3), Rockville, Maryland.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-1085.

Requests for Single Reprints: Roger Chou, MD, Oregon Health & Science University, Mailcode BICC, 3181 SW Sam Jackson Park Road, Portland, OR 97239; e-mail, chour@ohsu.edu.

Current author addresses and author contributions are available at http://www.annals.org.

Table 1. Summary of Evidence

Table 1. Summary of Evidence
Studies (n) and Overall Quality Limitations Consistency Applicability to Screening Population Summary of Findings
KQ 1. Does PSA-based screening decrease prostate cancer–specific or all-cause mortality?
5 RCTs

Overall quality: fair

Only 2 fair-quality RCTs; 1 additional fair-quality report from a center participating in 1 of the RCTs with substantial population overlap Low (inconsistent results between highest-quality trials) Some screening practices (interval and PSA thresholds) were different from typical U.S. practice PSA-based screening identifies more prostate cancers, but most trials found no effect on risk for death from prostate cancer. However, the 2 largest and highest-quality trials reported conflicting results. The ERSPC trial found PSA screening every 2–7 y to be associated with decreased risk for death from prostate cancer in a prespecified subgroup of men aged 55–69 y after 9 y (RR, 0.80 [95% CI, 0.65–0.98]; absolute risk reduction, 0.07 percentage point), but the PLCO trial found no effect after 10 y (RR, 1.1 [CI, 0.80–1.5]).

The PLCO trial had a relatively high rate of previous PSA testing (44%) and contamination in the control group (50% received ≥1 PSA test). The ERSPC trial varied in recruitment and randomization procedures, screening intervals, and PSA cut points among study centers. There were greater use of active treatments and more frequent screening intervals in the PLCO trial than the ERSPC trial.

A fair-quality study from 1 center participating in the ERSPC trial reported better results than the overall ERSPC analysis, with substantial overlap in patient populations. Three poor-quality screening trials did not find PSA-based screening to be associated with decreased risk for death from prostate cancer.

KQ 2. What are the harms of PSA-based screening for prostate cancer?
2 RCTs

Overall quality: fair

Randomized evidence available only from 2 fair-quality trials High Some screening practices (interval and PSA thresholds) differed from typical U.S. practice Reports from 2 fair-quality trials found false-positive rates of 12%–13% after 3–4 rounds of PSA-based screening, and 1 trial found that 76% of prostate biopsies identified no cancer. Serious infections or urine retention occurred after 0.5%–1.0% of prostate biopsies. Evidence was insufficient to estimate the magnitude of psychological harms associated with false-positive PSA test results.
KQ 3. What are the benefits of treatment of early-stage or screening-detected prostate cancer?
Prostatectomy
10 studies: 2 RCTs; 8 cohort studies

Overall quality: fair

Only 1 RCT High Prostate cancers in the RCT were primarily clinically detected rather than screening-detected, and there was a high proportion of stage T2 cancers; limited information was provided on specific surgical techniques evaluated Prostatectomy was associated with decreased risk for prostate cancer–specific mortality (RR, 0.62 [CI, 0.44–0.87]; absolute difference, 6.1 percentage points [CI, 0.2–12 percentage points]) and all-cause mortality (RR, 0.75 [CI, 0.61–0.92]; absolute difference, 6.6 percentage points [CI, -1.3 to 14 percentage points]) compared with watchful waiting after 15 y of follow-up in 1 good-quality RCT. Subgroup analysis suggests benefits are limited to men <65 y. Observational studies also found prostatectomy to be associated with decreased risk for death from prostate cancer (6 studies; median adjusted HR, 0.46 [range, 0.32–0.67]) and all-cause mortality (5 studies; median adjusted HR, 0.32 [range, 0.25–0.50]) after 4–13 y of follow-up compared with watchful waiting.
Radiation therapy
5 cohort studies

Overall quality: fair

No RCTs High Limited information provided on specific radiation therapy techniques and regimens evaluated Radiation therapy was associated with decreased risk for prostate cancer–specific mortality (5 studies; median adjusted HR, 0.66 [range, 0.63–0.70]) and all-cause mortality (5 studies; median adjusted HR, 0.68 [range, 0.62–0.81]) after 4–13 y of follow-up compared with watchful waiting.
KQ 4. What are the harms of treatment of early-stage or screening-detected prostate cancer?
Prostatectomy
18 studies: 1 RCT; 11 cohort studies; 6
uncontrolled observational studies

Overall quality: fair

Only 1 RCT of fair quality, unadjusted risk estimates for presence of urinary incontinence or erectile dysfunction from cohort studies Moderate Limited information provided on specific surgical techniques evaluated Prostatectomy was associated with increased risk for urinary incontinence compared with watchful waiting in 1 RCT (RR, 2.3 [CI, 1.6–3.2]; risk difference, 28%) and 4 cohort studies (median RR, 4.0 [range, 2.0–11]; median risk difference, 18 percentage points [range, 8–40 percentage points]). On the basis of large databases and surgical series, prostatectomy was associated with risk for perioperative death (about 0.5%) and cardiovascular events (0.6%–3%). Prostatectomy was not associated with worse outcomes on SF-36 summary component scores and most SF-36 subscales.
Radiation therapy
14 studies: 1 RCT; 13 cohort studies

Overall quality: fair

Only 2 RCTs, unadjusted risk estimates for presence of urinary incontinence or erectile dysfunction from cohort studies Moderate Limited information provided on specific radiation therapy techniques and regimens evaluated Radiation therapy was associated with increased risk for erectile dysfunction compared with watchful waiting in 6 cohort studies (median RR, 1.3 [range, 1.1–1.5]). Risk for urinary incontinence was increased in 1 RCT with a very imprecise estimate (RR, 8.3 [CI, 1.1–63]), but not in 4 cohort studies (median RR, 1.1 [range, 0.71–2.0]). Radiation therapy was also associated with an increased risk for bowel dysfunction, which appeared to improve over time. Radiation therapy was not associated with worse outcomes on SF-36 summary component scores and most SF-36 subscales.

ERSPC = European Randomized Study of Screening for Prostate Cancer; HR = hazard ratio; KQ = key question; PLCO = Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; PSA = prostate-specific antigen; RCT = randomized, controlled trial; RR = relative risk; SF-36 = Short-Form 36.

Appendix Figure 1. Summary of Literature Search and Selection: Effectiveness and Harms of Screening

Appendix Figure 1 entitled: 'Summary of Literature Search and Selection: Effectiveness and Harms of Screening'. Select Text Description below for details.

Appendix Figure 1. Summary of Literature Search and Selection: Effectiveness and Harms of Screening

[D] Select for Text Description.

Appendix Figure 1. Summary of Literature Search and Selection: Effectiveness and Harms of Screening (Text Description)

Appendix Figure 1, entitled: "Summary of literature search and selection: effectiveness and harms of screening," displays an accounting of studies reviewed for the first two key questions in the evidence report ("Does PSA-based screening decrease prostate cancer-specific or all-cause mortality?" and "What are the harms of PSA-based screening for prostate cancer?"). 379 unique articles were identified through searches of online databases and other sources as being potentially relevant to the evidence report. Of those, 278 were excluded at the title and 85 at the abstract level for not meeting inclusion criteria. The full text of 16 studies were reviewed for inclusion in the evidence report. Of those, 9 were excluded for not meeting inclusion criteria. The remaining 7 studies (in 8 publications) were included in the final evidence report.

Appendix Figure 2. Summary of Literature Search and Selection: Effectiveness and Harms of Treatment

Appendix Figure 2. Select Text Description below for details.

Appendix Figure 2. Summary of Literature Search and Selection: Effectiveness and Harms of Treatment

[D] Select for Text Description.

Appendix Figure 2. Summary of Literature Search and Selection: Effectiveness and Harms of Treatment (Text Description)

Appendix Figure 2, entitled: "Summary of literature search and selection: effectiveness and harms of treatment," displays an accounting of studies reviewed for the evidence report. 7,920 studies were identified through searches of online databases and other sources as being potentially relevant to the evidence report. Of those, 7,085 were excluded at the title or abstract level for not meeting inclusion criteria. The full text of 835 studies were reviewed for inclusion in the evidence report. Of those, 797 were excluded for not meeting inclusion criteria. The remaining 38 studies were included in the final evidence report. Of those, 11 studies were included for key question 1 and 27 studies were included for key question 2.

Appendix Table 1. Randomized, Controlled Trials of Prostate-Specific Antigen–Based Screening

Appendix Table 1. Randomized, Controlled Trials of Prostate-Specific Antigen–Based Screening
Study, Year (Reference) Study Population Study Sample Intervention Median/ Maximum Length of Follow-up, y Results Limitations Quality Rating Comments
ERSPC, 2009 7 Men in 7 European countries enrolled 1991–2003 182,160 men aged 50–74 y; 162,387 men in prespecified "core" subgroup aged 55–69 y

82,816 assigned to screening; 82% had ≥1 PSA test during trial

99,184 assigned to control group; based on single site, screening in controls ~20%

Variable by center; go toAppendix Table 2 for details

Most centers performed PSA every 4 y; some also used DRE or TRUS

PSA cut points were 2.5–10.0 µg/L; 3.0 µg/L most often used; some ancillary testing with lower PSA values

Positive screening result led to biopsy; treatments according to local policies and guidelines

9/14.5 No difference in prostate cancer–specific mortality in all enrolled men: RR, 0.85 (95% CI, 0.73–1.00)

Reduced prostate cancer–specific mortality in "core" subgroup: ARR, 0.071%; RR, 0.80 (CI, 0.65–0.98); NNS = 1410; NNT = 48

Inconsistencies in screening intervals and PSA thresholds among study centers

Methods of allocation concealment not described

Differences in exclusion of men by age between centers

Exclusion of data from 2 study centers (Portugal and France, which would bring the number of participating countries to 9)

Inadequate reporting of attrition

Fair  
Substudy of ERSPC (Göteborg), 2010 21 Men born between 1930 and 1944 identified from the population register of Göteborg, Sweden in December 1994 19,904 men aged 50–64 y

9952 invited to screening; 76% had at least 1 PSA test

9952 controls not invited to screening; contamination rate estimated at 3%

PSA every 2 y for 7 rounds

PSA cut point 2.5–3.0 µg/L, depending on year

Positive screening result led to DRE, TRUS, and biopsy

Treatment was at the discretion of the participant's personal physician

14/14 Reduced prostate cancer–specific mortality: ARR, 0.40% (CI, 0.17%–0.64%); RR, 0.56 (CI, 0.39–0.82); NNS = 293 (CI, 177–799); NNT = 12 60% of participants (men born between 1930 and 1939) previously included in overall ERSPC results

No baseline sociodemographic comparison of the 2 groups

Inadequate reporting of attrition

Contamination rate in controls not formally assessed; unclear how 3% estimate obtained

Fair This publication represents single-center results reported separately from the overarching ERSPC trial
Sandblom et al, 2004 19, 2011 20 Male residents of Norrköping, Sweden identified in the Swedish National Population Register in 1987 9026 men aged 50–69 y

1494 men (every sixth man) invited for screening; 70%–78% received screening, depending on year

7532 controls received usual care; unknown how many received screening

DRE only in 1987 and 1990

DRE and PSA in 1993 and 1996

PSA cut point >4.0 µg/L

Positive result on screening test led to biopsy; confirmed prostate cancer treated according to regional standardized management program

6.3/20 No difference in prostate cancer–specific mortality (RR, 1.16 [CI, 0.78–1.73]) or overall survival (log-rank test P = 0.14) between invited and noninvited groups Inadequate randomization and allocation concealment procedure (predictable group assignment)

No comparison of baseline sociodemographic characteristics of the 2 groups

Contamination rate in control group not assessed

Inadequate reporting of attrition

Poor Trial included in the 2008 evidence review and previously considered by the USPSTF
PLCO, 2009 6 Men enrolled at 10 study centers in the United States 1993–2001 76,693 men aged 55–74 y

38,343 men assigned to screening; overall adherence to screening was 85% for PSA and 86% for DRE

38,350 men assigned to usual care; 52% had ≥1 PSA test during trial

Annual PSA for 6 y

Annual DRE for 4 y

PSA cut point >4.0 µg/L

Positive PSA or DRE result referred to patient's primary care physician for management

11.5/14.8 No difference in prostate cancer–specific mortality at 7 or 10 y: rate ratios, 1.13 (CI, 0.75–1.70) and 1.11 (CI, 0.83–1.50), respectively

No difference in overall mortality (excluding from prostate, lung, or colorectal cancer) at 7 or 10 y: rate ratios, 0.98 (CI, 0.92–1.03) and 0.97 (CI, 0.93–1.01), respectively

High rate of contamination in control group (up to 52% by 6 y)

Approximately 44% of men in each group had undergone ≥1 PSA test before trial entry

Fair  
Labrie et al, 2004 17 Men registered on the Quebec City area electoral rolls in 1988 46,486 men aged 45–80 y

31,133 men invited for screening; 23.6% received screening

15,353 controls not invited; 7.3% received screening

DRE and PSA at first visit

PSA alone at subsequent screenings

PSA cut point >3.0 µg/L; if PSA previously >3.0 µg/L, a PSA increase of 20% over previous year's value or over predicted PSA

Positive screening test result led to TRUS-guided biopsy

7.9/11 No difference in prostate cancer–specific mortality when data are analyzed via intention-to-screen: RR, 1.01 (CI, 0.82–1.40) No information to assess adequacy of randomization or allocation concealment

Unclear whether outcome assessment was blinded

No baseline sociodemographic comparison of the 2 groups

Inadequate reporting of attrition

Authors did not primarily use intention-to-screen analysis

Poor Trial included in the 2008 evidence review and previously considered by the USPSTF
Kjellman et al, 2009 16 Men living in the catchment area of Stockholm South Hospital in Sweden in 1988 26,602/27,204 men aged 55–70 y

2400 men invited for screening, 74% received screening

24,202/24,804 controls from source population received usual care; contamination not reported

Single screening with DRE, TRUS, and PSA

Abnormal DRE or TRUS led to biopsy

PSA cut point >7.0 ng/mL led to repeat TRUS

PSA cut point >10.0 µg/L led to biopsy

Treatment was "the standard care at the clinic at that time"

12.9/15.7 No difference in prostate cancer–specific mortality: IRR, 1.10 (CI, 0.83–1.46)

No difference in death from other causes: IRR, 0.98 (CI, 0.92–1.05)

Methods of randomization and allocation concealment unclear

Unclear whether outcome assessment was blinded

No baseline sociodemographic comparison of the 2 groups

Contamination rates in control group not assessed

Inadequate reporting of attrition

Limited applicability to current U.S. practice (high PSA threshold)

Poor Report has internal discrepancies about the total number in the original cohort because the file containing the registration numbers of the original cohort could not be retrieved

ARR = absolute risk reduction; DRE = digital rectal examination; ERSPC = European Randomized Study of Screening for Prostate Cancer; IRR = incidence rate ratio; NNS = number needed to screen; NNT = number needed to treat; PLCO = Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; PSA = prostate-specific antigen; RR = relative risk; TRUS = transrectal ultrasonography; USPSTF = U.S. Preventive Services Task Force.

Appendix Table 2. Studies of Treatments for Localized Prostate Cancer

Appendix Table 2. Studies of Treatments for Localized Prostate Cancer
Study, Year (Reference) Interventions Definition of Watchful Waiting Mean Duration of Follow-up Mean Age, y Stage at Diagnosis Variables Adjusted for in Analysis Outcomes Quality Score
RCTs
Bill-Axelson et al, 2011 23 
Other publications: 
Johansson et al, 2009 41; Bill-Axelson et al, 2008 22; Holmberg et al, 2006 27; Bill-Axelson et al, 2005 24; Steineck et al, 2002 42; Holmberg et al, 2002 28
Watchful waiting (n = 348)
Radical prostatectomy (n = 347)
No immediate treatment 13 y (range, 3 wk–20.2 y); 15-y estimates reported 65 T1b: 12% (83/695)
T1c: 12% (81/695)
T2: 76% (529/695)
Unknown: T2 <1% (2/695) 
Mean PSA level: 12.9 µg/L
NA (RCT) Prostate cancer–specific mortality
All-cause mortality
Good
Fransson et al, 2001 39 
Other publications:
Fransson et al, 2009 40
Watchful waiting (n = 27)
Radiation therapy (n = 27)
Regular monitoring and deferred treatment until time of progression 10 y 78 T1: 25% (14/57)
T2: 75% (43/57)
NA (RCT) Disease-specific quality of life
Generic quality of life
Fair
Iversen et al, 1995 29
Other publications: Byar and Corle, 1981 25; Graversen et al, 1990 26
Watchful waiting (n = 68)
Radical prostatectomy (n = 74)
Oral placebo, no other treatment 23 y (range, 19–27 y) 64 WHO stage I: 54% (76/142) 
WHO stage II: 46% (66/142)
NA (RCT) All-cause mortality Poor
Cohort studies
Albertsen et al, 2007 30 No initial therapy (n = 114)
Surgery (n = 802)
Radiation (n = 702)
Observation only (not defined) Varied according to treatment group: median, 13.1–13.6 y 68 Gleason score 2–4: 4% 
Gleason score 5: 6%
Gleason score 6: 47%
Gleason score 7: 26%
Gleason score 8–10: 17%
Gleason score, PSA, clinical stage, age at diagnosis, and Charlson comorbidity score Prostate cancer–specific mortality Fair
Bacon et al, 2001 43 Watchful waiting (n = 31)
Prostatectomy (n = 421)
EBRT (n = 221)
Brachytherapy (n = 69)
Hormone (n = 33)
Other* (n = 67)
Not defined 5 y 71 T1: 3% (23/842)
T2: 86% (726/842) 
Other: 11% (93/842)
Age, marital status, waist circumference, metabolic equivalent hours of physical activity/wk, smoking status, alcohol intake, comorbid conditions, Gleason score Disease-specific quality of life
Generic quality of life
Fair
Choo et al, 2010 44 Watchful waiting (n = 9)
Radiation therapy (n = 52; EBRT, n = 22; brachytherapy, n = 30)
Not defined 2 y 64 Tx: 4% (3⁄75)
T1: 55% (41⁄75)
T2: 37% (28⁄75) 
T3: 4% (3⁄75)
No adjustment for variables; adjustment made for repeat measures Disease-specific quality of life Fair
Galbraith et al, 2001 46 Watchful waiting (n = 30)
Surgery (n = 59)
Conventional radiation (n = 25)
Proton-beam radiation (n = 24)
Mixed-beam radiation (n = 47)
Not defined 2 y 68 Stage NR (mean PSA values ranged from 9.8 to 17.6 µg/L at baseline depending on treatment group) No adjustment for variables Disease-specific quality of life
Generic quality of life
Fair
Hoffman et al, 2003 47 No treatment (n = 230)
Androgen deprivation (n = 179)
Radiation (n = 583)
Radical prostatectomy (n = 1373)
No active treatment 2 y 66 Stage NR (all were T1 or T2) Demographic, socioeconomic, and clinical variables (not further defined) Disease-specific quality of life Fair
Ladjevardi et al, 2010 31 Conservative management (watchful waiting [n = 935] and palliative treatment, including androgen deprivation [n = 3210])
Radical prostatectomy (n = 12,950)
Radiation therapy (n = 6308; EBRT, n = 4443; and brachytherapy, n = 1865)
Not defined Median, 4 y (range, 0–12 y) 65 T0: <1% 
T1: 49% 
T2: 35% 
T3: 15% 
Tx: <1%
Age, Gleason score, PSA All-cause mortality Fair
Litwin et al, 1995a 48

Other publication: Litwin et al, 1995b 49
Observation (n = 60)
Prostatectomy (n = 98)
Radiation (n = 56)
Not defined 6 y 73 Tumor stage NR (all were clinically localized) Age; comorbid conditions (diabetes, cardiovascular disease, respiratory disease, gastrointestinal disease, renal disease, depression, alcohol or drug problems, smoking) Disease-specific quality of life
Generic quality of life
Fair
Litwin et al, 2002 50 Watchful waiting (n = 66)
Radical prostatectomy (n = 282)
Radiation (n = 104)
Not defined 2 y 66 T1: 30% (136/452)
T2: 66% (298/452) 
T3/4 or N+ or M+:
4% (18/452)
Comorbid conditions, PSA, Gleason score, age Generic quality of life Fair
Lu-Yao et al, 2008 32 Conservative management (n = 11,404) 
Primary ADT (n = 7867)
No use of surgery, radiation, or ADT Median, 7 y 78 T1: 58%
T2: 42%
Instrumental variable analysis (covariates in analysis included age, race, comorbidity status, cancer stage, cancer grade, income status, urban resident, marital status, and year of diagnosis) Prostate cancer–specific mortality
All-cause mortality
Fair
Lubeck et al, 1999 51 Observation (n = 87)
Prostatectomy (n = 351)
Radiation therapy (n = 75)
No surgery, radiation, or medical therapy in the first year after diagnosis 2 y 66 T1: 25% (174/692)
T2: 62% (427/692)
T3/T4: 5% (33/179) 
Other: 8% (52/692)
Time (mixed model used to evaluate rate of quality-of-life change); age Disease-specific quality of life
Generic quality of life
Fair
Merglen et al, 2007 33 Watchful waiting (n = 378)
Prostatectomy (n = 158)
Any EBRT (n = 205; EBRT alone, n = 152; EBRT + ADT, n = 53)
ADT (n = 72)
Other treatment (n = 31; not described)
Active follow-up with treatment for disease progression 7 y 71 Stage 1: 29% 
Stage 2: 40% 
Stage 3: 31% 
PSA < 10 µg/L: 22%
PSA 11–29 µg/L: 28%
PSA > 30 µg/L: 23%
PSA unknown: 27%
Age, period of diagnosis, method of detection, lymph node status, clinical tumor stage, differentiation, and PSA level Prostate cancer–specific mortality
All-cause mortality
Fair
Potosky et al, 2002 52 Observation (n = 416)
ADT (n = 245)
No therapy 1 year Mean age, NR
40–59 y: 4% (27/661) 
60–69 y: 22% (145/661)
70–79 y: 53% (350/661)
≥80 y: 21% (139/661)
T1: 33% (221/661) 
T2: 51% (338/661) 
Unknown: 15% (101/661)
Sociodemographic and clinical characteristics, presence of sexual partner, impotence, comorbid conditions, prostate cancer symptoms Disease-specific quality of life
Generic quality of life
Good
Schapira et al, 2001 53 Expectant management (n = 29)
Radical prostatectomy (n = 42)
Radiation therapy (n = 51)
Not defined 1 y Median age, 69 T1: 50% (61/122) 
T2: 50% (61/122)
Comorbid conditions, stage, age, years of education, race, marital status, employment status Disease-specific quality of life Generic quality of life Fair
Schymura et al, 2010 34 Watchful waiting (n = 614)
Radical prostatectomy (n = 1310)
Radiation therapy (EBRT or brachytherapy; n = 1037)
ADT (n = 339)
No therapy within 6 mo of diagnosis 5 y Mean age NR;
<60 y: 18% 60–64 y: 17%
65–69 y: 22%
70–74 y: 21% 
75–79 y: 14% 
≥80 y: 8%
PSA < 10 µg/L: 57% 
PSA 10–20 µg/L: 26% 
PSA > 20 µg/L: 11% PSA unknown: 13%
Age at diagnosis, race/ethnicity, marital status, state, PSA value, Gleason score, comorbidity score, time since diagnosis Disease-specific quality of life
Generic quality of life
Fair
Siegel et al, 2001 54 Watchful waiting (n = 64) 
Radical prostatectomy (n = 419)
EBRT (n = 319)
Follow-up every 3–4 mo for 1 y, every 6 mo subsequently 4 y 66 Grade A: 7% (58/802)
Grade B: 89% (713/802)
Unknown: 4% (31/802)
No adjustment for variables Disease-specific quality of life Fair
Smith et al, 2000 55 Observation (n = 120)
Radical prostatectomy (n = 1247)
Radiation therapy (n = 189)
Hormonal therapy (n = 67)
Cryotherapy (n = 28)
Not defined 4 y 67 T1/T2: 98% 
(2194/2234)
T3: <1% (9/2234) 
T4: 1% (29/2234)
Age, current comorbid conditions, education, time since diagnosis Disease-specific quality of life
Generic quality of life
Fair
Smith et al, 2009 56 Active surveillance (n = 200)
Radical prostatectomy (n = 981)
EBRT (n = 123)
ADT (n = 61)
Combined EBRT/ADT (n = 166)
Low-dose brachytherapy (n = 58)
High-dose brachytherapy (n = 47)
Active surveillance (not further defined) 3 y 61 T1: 54% (889/1636)
T2: 46% (747/1636)
Age, insurance status, comorbidity score, stage, Gleason score, PSA Disease-specific quality of life
Generic quality of life
Good
Stattin et al, 2010 35 Surveillance (n = 2021)
Radical prostatectomy (n = 3399)
Radiation (n = 1429)
Combined active surveillance and watchful waiting (no further definition) Median, 8.2 y 63 T1: 59% 
T2: 41% 
Mean PSA: 8.2 µg/L
Prostate cancer risk category, Charlson comorbidity index, socioeconomic status Prostate cancer–specific mortality
All-cause mortality
Fair
Talcott et al, 2003 57

Other publication: Clark and Talcott, 2001 45
Observation (n = 19)
Radical prostatectomy (n = 129)
EBRT (n = 182)
Brachytherapy (n = 80)
Not defined 2 y 65 Exact proportion of patients with T1 and T2 unclear because of reporting method; most (>70%) were T1 Age, D'Amico risk category, marital status, education, other variables (not defined) Disease-specific quality of life Fair
Tewari et al, 2007 36 Conservative management (n = 197)
Radiation therapy (n = 137)
Radical prostatectomy (n = 119)
Not defined 5 y 63 Stage 3: 100% Propensity analysis (propensity score based on age at diagnosis, race, socioeconomic status, Charlson comorbidity index, and year of diagnosis) Prostate cancer–specific mortality
All-cause mortality
Fair
Thong et al, 2010 58 Active surveillance (n = 71)
EBRT (n = 71)
Stage and tumor grade ≤2 at time of diagnosis, no active treatment 5–10 y 76 T1: 80% (114/142) 
T2: 20% (28/142)
Demographic and clinical characteristics Disease-specific quality of life
Generic quality of life
Good
Wong et al, 2006 37 Observation (n = 12,608)
Active treatment (n = 32,022; includes radical prostatectomy [n = 13,292] and EBRT or brachytherapy [n = 18,249], alone or in combination)
No Medicare data for prostatectomy, radiation, or hormonal therapy 12 y 72 Stage ≤T2a: 55%
Stage T2b–T2c: 45%
Propensity-adjusted (propensity score based on age at diagnosis, SEER site, year of diagnosis, tumor size, tumor grade, marital status, residence in urban setting, race, income, educational achievement, and comorbid conditions) All-cause mortality Fair
Zhou et al, 2009 38 No treatment (n = 1716)
Monotherapy
Radical prostatectomy (n = 889)
EBRT (n = 783)
Brachytherapy (n = 595)
ADT (n = 2049)
Combination therapy
Radical prostatectomy + EBRT, ADT, or both (n = 181)
EBRT + ADT (n = 1286)
Brachytherapy + EBRT or ADT (n = 756)
No definitive therapy within 6 mo of diagnosis 7 y Mean age NR; for total cohort (including 1924 patients with distant or unknown stage):
65–69 y: 21% 
70–74 y: 32%
≥75 y: 46%
66% Gleason score <7 Age, race, tumor stage, Gleason score, pretreatment comorbidity Prostate cancer–specific mortality Fair

ADT = androgen deprivation therapy; EBRT = external-beam radiation therapy; NA = not applicable; NR = not reported; PSA = prostate-specific antigen; RCT = randomized, controlled trial; SEER = Surveillance, Epidemiology, and End Results; WHO = World Health Organization.
* Definition unclear; results not abstracted.
 Conservatively managed patients included those who received ADT.
 Results from the hormone therapy group were not abstracted; 32% (57/179) were at stage T3 or higher at baseline

Appendix Table 3. Prostate Cancer–Specific and All-Cause Mortality

Appendix Table 3. Prostate Cancer–Specific and All-Cause Mortality
Study, Year (Reference), and 
Duration of Follow-up
Prostate Cancer–Specific Mortality All-Cause Mortality
RCTs Prostatectomy vs. watchful waiting Prostatectomy vs. watchful waiting
Bill-Axelson et al, 2011 23

Other publications:
Bill-Axelson et al, 2008 22; Holmberg et al, 2006 27; Bill-Axelson et al, 2005 24; Steineck et al, 2002 42; Holmberg et al, 2002 28

Follow-up duration: 13 y

15% (CI, 11%–19%) vs. 21% (CI, 17%–26%); HR, 0.62 (CI, 0.44–0.87)

Subgroups: Risk
6.5% (CI, 3.5%–14%) vs. 11% (CI, 6.8%–18%); HR, 0.53 (CI, 0.24–1.1)

Subgroups: Age
Age < 65 y: 16% (CI, 11%–24%) vs. 26% (CI, 20%–34%); HR, 0.49 (CI, 0.31–0.79)
Age ≥ 65 y: 13% (CI, 8.9%–19%) vs. 16% (CI, 11%–23%); HR, 0.83 (CI, 0.50–1.3)

Subgroups: Risk + age
Age < 65 y and low-risk: 7.1% (CI, 2.7%–19%) vs. 12% (CI, 6.0%–23%); HR, 0.41 (CI, 0.14–1.2)
Age ≥ 65 y and low-risk: 6.6% (CI, 2.5%–17%) vs. 10% (CI, 5.1%–21%); HR, 0.76 (CI, 0.35–2.3)

46% (CI, 41%–52%) vs. 53% (CI, 47%–59%); HR, 0.75 (CI, 0.61–0.92)

Subgroups: Risk
Low-risk: 31% (CI, 24%–41%) vs. 45% (37%–54%); HR, 0.62 (CI, 0.42–0.92)

Subgroups: Age
Age < 65 y: 34% (CI, 27%–43%) vs. 47% (CI, 40%–56%); HR, 0.52 (CI, 0.37–0.73)
Age ≥ 65 y: 57% (CI, 50%–65%) vs. 57% (CI, 50%–66%); HR, 0.98 (CI, 0.75–1.3)

Subgroups: Risk + age
Age < 65 y and low-risk: 17% (CI, 9.5%–30%) vs. 36% (CI, 26%–50%); HR, 0.36 (CI, 0.18–0.7)
Age ≥ 65 y and low-risk: 47% (CI, 35%–62%) vs. 53% (CI, 41%–68%); HR, 0.92 (CI, 0.57–1.5)

Iversen et al, 1995 29

Other publications: Byar and Corle, 1981 25; Graversen et al, 1990 26

Follow-up duration: 23 y

NR Median duration of survival: 8 y vs. 11 y; P > 0.05
Cohort studies Prostatectomy vs. watchful waiting Prostatectomy vs. watchful waiting
Albertsen et al, 2007 30

Follow-up duration: 13 y

14% vs. 4%; RR, 3.4 (CI, 1.9–5.9) NR
Ladjevardi et al, 2010 31

Follow-up duration: 4 y

NR HR, 0.41 (CI, 0.36–0.48)

Subgroups: Risk
Gleason score 7: HR, 0.78 (CI, 0.63–0.97)
Gleason score 8–10: HR, 0.65 (CI, 0.47–0.90)

Merglen et al, 2007 33

Follow-up duration: 7 y

5-y mortality: 8/158 (5%) vs. 43/378 (11%); HR, 0.56 (CI, 0.24–1.3)
10-y mortality: 15/158 (9%) vs. 70/378 (11%); HR, 0.59 (CI, 0.26–0.91)

Subgroups: Risk
10-y mortality, Gleason score <7: 9/112 (8%) vs. 31/225 (14%); HR, 0.5 (CI, 0.22–1.1)
10-y mortality, Gleason score ≥7: 4/31 (13%) vs. 28/76 (37%); HR, 0.23 (CI, 0.06–0.91)

Subgroups: Age
10-y mortality, age <70 y: 5/118 (4%) vs. 13/104 (13%); HR, 0.12 (CI, 0.04–0.42) 
10-y mortality, age ≥70 y: 10/40 (25%) vs. 57/274 (21%); HR, 1.25 (CI, 0.59–2.5)

5-y mortality: 21/158 (13%) vs. 147/378 (39%); HR, 0.71 (CI, 0.4–1.4)
10-y mortality: 34/158 (22%) vs. 223/378 (60%); HR, 0.67 (CI, 0.4–1.1)
Schymura et al, 2010 34

Follow-up duration: 5 y

NR 6% vs. 25%; HR, 0.44 (CI, 0.33–0.59)
Stattin et al, 2010 35

Follow-up duration: 8 y

2.4% (CI, 1.8%–3.3%) vs. 3.6% (CI, 2.7%–4.8%); HR, 0.49 (CI, 0.34–0.71)

Subgroups: Risk
Low-risk: 0.4% (CI, 0.13%–0.97%) vs. 2.4% (CI, 1.2%–4.1%); HR, 0.29 (CI, 0.09–0.87)
Intermediate-risk: 3.4% (CI, 2.5%–4.7%) vs. 5.2% (CI, 3.7%–6.9%); HR, 0.53 (CI, 0.35–0.80)

11% (CI, 10%–13%) vs. 23% (CI, 21%–26%); HR, 0.49 (CI, 0.41–0.57)
Tewari et al, 2007 36

Follow-up duration: 4–6 y*

18/119 (15%) vs. 85/197 (43%); HR, 0.31 (CI, 0.17–1.2) 27/119 (23%) vs. 139/197 (71%); HR, 0.32 (CI, 0.20–0.51)
Wong et al, 2006 37

Follow-up duration: 12 y

NR HR, 0.50 (CI, 0.47–0.53)
Zhou et al, 2009 38

Follow-up duration: 7 y

HR, 0.25 (CI, 0.13–0.48) NR
Cohort studies Radiation therapy vs. watchful waiting Radiation therapy vs. watchful waiting
Albertsen et al, 2007 30

Follow-up duration: 13 y

9% vs. 14%; rate ratio, 1.5 (CI, 0.9–2.6) NR
Ladjevardi et al, 2010 31

Follow-up duration: 4 y

NR HR, 0.62 (CI, 0.54–0.71)

Subgroups: Risk
Gleason score 7: HR, 0.81 (CI, 0.66–0.99)
Gleason score 8–10: HR, 0.71 (CI, 0.55–0.92)

Stattin et al, 2010 35

Follow-up duration: 8 y

3.3% (CI, 2.5%–5.7%) vs. 3.6% (CI, 2.7%–4.8%); HR, 0.70 (CI, 0.45–1.1)

Subgroups: Risk
Low-risk: 1.8% (CI, 0.65 to 4.0) vs. 2.4% (CI, 1.2%–4.1%); HR, 0.94 (CI, 0.31–2.85)
Intermediate-risk: 3.8% (CI, 2.6%–5.4%) vs. 5.2% (CI, 3.7%–6.9%); HR, 0.66 (CI, 0.42–1.1)

18% (CI, 16%–21%) vs. 23% (CI, 21%–26%); HR, 0.68 (CI, 0.057–0.82)
Tewari et al, 2007 36

Follow-up duration: 4-6 y*

23/137 (17%) vs. 85/197 (43%); HR, 0.63 (CI, 0.38–1.1) 58/137 (42%) vs. 139/197 (71%); HR, 0.70 (CI, 0.50–0.99)
Wong et al, 2006 37

Follow-up duration: 12 y

NR HR, 0.81 (CI, 0.78–0.85)
Zhou et al, 2009 38

Follow-up duration: 7 y

EBRT: HR, 0.66 (CI, 0.41–1.0)
Brachytherapy: HR, 0.45 (CI, 0.23–0.87)
EBRT + ADT: HR, 0.97 (CI, 0.70–1.33)
Brachytherapy + EBRT or ADT: HR, 0.46 (CI, 0.27–0.8)
EBRT: HR, 0.63 (CI, 0.53–0.75)
Brachytherapy: HR, 0.4 (CI, 0.32–0.52)
EBRT + ADT: HR, 0.57 (CI, 0.49–0.66)
Brachytherapy + EBRT or ADT: HR, 0.32 (CI, 0.26–0.41)
Cohort studies ADT vs. watchful waiting ADT vs. watchful waiting
Lu-Yao et al, 2008 32

Follow-up duration: 7 y

867/32,744 (rate, 2.6/100) events per person-year vs. 693/55,424 (rate, 1.3/100) events per person-year; HR, 1.8 (CI, 1.6–1.9)

Subgroups: Risk
Moderately differentiated tumors: HR, 1.8 (CI, 1.6–2.1)
Poorly differentiated tumors: HR, 1.1 (CI, 1.0–1.3)

4729/39,767 (rate, 11.9/100) events per person-year vs. 6316/66,567 (rate, 9.5/100) events per person-year; HR, 1.2 (CI, 1.1–1.2)

Subgroups: Risk
Moderately differentiated tumors: HR, 1.2 (CI, 1.1–1.2)
Poorly differentiated tumors: HR, 1.0 (CI, 1.0–1.1)

Zhou et al, 2009 38

Follow-up duration: 7 y

HR, 1.3 (CI, 1.0–1.7) HR, 0.91 (CI, 0.83–1.0)

ADT = androgen deprivation therapy; EBRT = external-beam radiation therapy; HR = hazard ratio; NR = not reported; RCT = randomized, controlled trial; RR = relative risk.
* Duration varied by treatment group.

Appendix Table 4. Erectile Dysfunction and Urinary Incontinence

Appendix Table 4. Erectile Dysfunction and Urinary Incontinence
Study, Year (Reference) Urinary Incontinence Erectile Dysfunction
RCTs Prostatectomy vs. watchful waiting Prostatectomy vs. watchful waiting
Johansson et al, 2009 41
Steineck et al, 2002 42 
Follow-up duration: 2–8 y
Urinary incontinence 
49% (79/162) vs. 21% (33/155); RR, 2.3 (CI, 1.6–3.2)
Erectile dysfunction
81% (128/159) vs. 45% (71/158); RR, 1.8 (CI, 1.5–2.2)
Cohort studies Prostatectomy vs. watchful waiting Prostatectomy vs. watchful waiting
Hoffman et al, 2003 47 
Follow-up duration: 2 y
Urinary leakage, daily or more often
35% (484/1373) vs. 8% (19/230); RR, 4.3 (CI, 2.8–6.6)
No erections 
55% (757/1373) vs. 26% (60/230); RR, 2.1 (CI, 1.7–2.6)
Litwin et al, 1995b 49 
Follow-up duration: 6 y
No urinary control or frequent dribbling
19% (19/98) vs. 10% (6/60); RR, 1.9 (CI, 0.82–4.6)
Poor or very poor sexual function 
78% (76/98) vs. 52% (31/60); RR, 1.5 (CI, 1.2–2.0)
Schapira et al, 2001 53
Follow-up duration: 1 y
Urinary incontinence
44% (16/36) vs. 4% (1/25); RR, 11 (CI, 1.6–78)
Impotence 
89% (33/37) vs. 68% (17/25); RR, 1.3 (CI, 0.98–1.8)
Siegel et al, 2001 54 
Follow-up duration: 4 y
NR Erection insufficient for intercourse 
90% (353/392) vs. 63% (40/64); RR, 1.4 (CI, 1.2–1.8)
Smith et al, 2009 56 
Follow-up duration: 3 y
Urinary incontinence
12% (111/981) vs. 3% (6/200); RR, 3.7 (CI, 2.4–5.7)
Impotence 
71% (695/981) vs. 47% (94/200); RR, 1.5 (CI, 1.3–1.8)
RCTs Radiation therapy vs. watchful waiting Radiation therapy vs. watchful waiting
Fransson et al, 2009 40 
Follow-up duration: 3 y
Urinary incontinence, proportion of patients using pads 
17% (10/59) vs. 2% (1/49); RR, 8.3 (CI, 1.1–63)
NR
Cohort studies Radiation therapy vs. watchful waiting Radiation therapy vs. watchful waiting
Hoffman et al, 2003 47
Follow-up duration: 2 y
Urinary leakage, daily or more often 
12% (71/583) vs. 8% (19/230); RR, 1.5 (CI, 0.91–2.39)
No erections at all 
39% (228/583) vs. 26% (60/230); RR, 1.5 (CI, 1.2–1.9)
Litwin et al, 1995b 49
Follow-up duration: 6 y
No urinary control or frequent dribbling 
7% (4/56) vs. 10% (6/60); RR, 0.71 (CI, 0.21–2.4)
Poor or very poor sexual function 
66% (39/59) vs. 52% (31/60); RR, 1.28 (CI, 0.94–1.7)
Schapira et al, 2001 53 
Follow-up duration: 1 y
Urinary incontinence 
8% (3/38) vs. 4% (1/25); RR, 2.0 (CI, 0.22–18)
Impotence
75% (30/40) vs. 68% (17/25); RR, 1.1 (CI, 0.80–1.5)
Siegel et al, 2001 54
Follow-up duration: 4 y
NR Erection insufficient for intercourse 
85% (269/315) vs. 63% (40/64); RR, 1.4 (CI, 1.1–1.7)
Smith et al, 2009 56 
Follow-up duration: 3 y
Urinary incontinence 
2% (3/123) vs. 3% (6/200); RR, 0.81 (CI, 0.21–3.2)
Impotence 
59% (72/123) vs. 47% (94/200); RR, 1.2 (CI, 1.0–1.5)
Thong et al, 2010 58
Follow-up duration: 5-10 y
NR Problem getting an erection nearly all the time
68% (43/63) vs. 47% (28/60); RR, 1.5 (CI, 1.1–2.0)
Cohort studies ADT vs. watchful waiting ADT vs. watchful waiting
Hoffman et al, 2003 47 
Follow-up duration: 2 y
Urinary leakage daily or more often 
11% (20/179) vs. 8% (19/230); RR, 1.4 (CI, 0.74–2.5)
No erections at all 
75% (135/179) vs. 26% (60/230); RR, 2.9 (CI, 2.3–3.6)
Potosky et al, 2002 52 
Follow-up duration: 1 y
NR Impotence 
77% (68/88) vs. 27% (60/223); RR, 2.9 (CI, 2.2–3.7)
Smith et al, 2009 56 
Follow-up duration: 3 y
Urinary incontinence
3% (2/61) vs. 3% (6/200); RR, 1.1 (CI, 0.23–5.3)
Impotence 
74% (45/61) vs. 47% (94/200); RR, 1.6 (CI, 1.3–1.9)

ADT = androgen deprivation therapy; NR = not reported; RCT = randomized, controlled trial; RR = relative risk.

Appendix Table 5. Summary Scores for Disease-Specific and Generic Health-Related Quality of Life

Appendix Table 5. Summary Scores for Disease-Specific and Generic Health-Related Quality of Life
  Radical Prostatectomy vs. Watchful Waiting Radiation Therapy vs. Watchful Waiting ADT vs. Watchful Waiting
Scale Studies, n 
(References)
Median Difference in Mean Scores
(Range)
Studies, n 
(References)
Median Difference in Mean Scores
(Range)
Studies, n 
(References)
Median Difference in Mean Scores
(Range)
UCLA-PCI scores
Urinary function 6 43, 48, 51, 53, 55, 56 -18 (-30 to -9) 7 43, 48, 51, 53, 55, 56, 58 -4 (-5 to 1) 3 43, 55, 56 -4 (-9 to 1)
Urinary bother 6 43, 48, 51, 53, 55, 56 -8 (-17 to -1) 7 43, 48, 51, 53, 55, 56, 58 -3 (-19 to 3) 3 43, 55, 56 -11 (-17 to -5)
Sexual function 6 43, 48, 51, 53, 55, 56 -19 (-34 to -2) 6 43, 38, 51, 53, 55, 56 -11 (-20 to -4) 3 43, 55, 56 -31 (-36 to -29)
Sexual bother 6 43, 48, 51, 53, 55, 56 -27 (-35 to 22) 6 43, 38, 51, 53, 55, 56 -5 (-18 to 17) 3 43, 55, 56 -15 (-20 to 1)
Bowel function 5 43, 48, 51, 53, 56 -1 (-5 to 2) 6 43, 48, 51, 53, 56, 58 -4 (-7 to 1) 2 43, 56 Not calculated (-10 and -5)
Bowel bother 5 43, 48, 51, 53, 56 0 (-5 to 5) 6 43, 48, 51, 53, 56, 58 -6 (-15 to 6) 2 43, 56 Not calculated (-6 and -1)
SF-36 scores
Physical component summary score 2 43, 56 Not calculated (2 and 3) 3 43, 56, 58 0 (-3 to 0) 2 43, 56 Not calculated (-8 and -3)
Mental component summary score 2 43, 56 Not calculated (0 and 1) 3 43, 56, 58 0 (-2 to 1) 2 43, 56 Not calculated (-3 and 0)
Physical function 6 43, 46, 48, 51, 53, 55 8 (2 to 16) 7 43, 46, 48, 51, 53, 55, 58 -5 (-10 to 4) 2 43, 56 Not calculated (-7 and 3)
Physical role function 6 43, 46, 48, 51, 53, 55 2 (-10 to 9) 7 43, 46, 48, 51, 53, 55, 58 -9 (-22 to 1) 3 43, 52, 56 -11 (-23 to -11)
Bodily pain 6 43, 46, 48, 51, 53, 55 3 (-5 to 10) 7 43, 46, 48, 51, 53, 55, 58 -5 (-11 to 0) 3 43, 52, 56 -6 (-8 to -1)
General health 6 43, 46, 48, 51, 53, 55 4 (2 to 21) 7 43, 46, 48, 51, 53, 55, 58 1 (-9 to 3) 2 43, 56 Not calculated (-5 and -2)
Vitality 7 43, 46, 48, 50, 51, 53, 55 3 (-2 to 14) 8 43, 46, 48, 50, 51, 53, 55, 58 -4 (-5 to 1) 3 43, 52, 56 -7 (-7 to -7)
Social function 6 43, 48, 50, 51, 53, 55 3 (-2 to 11) 7 43, 46, 48, 51, 53, 55, 58 -2 (-9 to 1) 2 43, 56 Not calculated (-10 and -4)
Emotional role function 7 43, 46, 48, 50, 51, 53, 55 8 (-5 to 13) 8 43, 46, 48, 50, 51, 53, 55, 58 -4 (-9 to 19) 3 43, 52, 56 -15 (-16 to -3)
Mental health 7 43, 46, 48, 50, 51, 53, 55 -1 (-4 to 10) 8 43, 46, 48, 50, 51, 53, 55, 58 -2 (-6 to 2) 3 43, 52, 56 -4 (-6 to 0)

ADT = androgen deprivation therapy; SF-36 = Short-Form 36; UCLA-PCI = University of California, Los Angeles, Prostate Cancer Index.

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Current as of: October 2011

Internet Citation: Evidence Summary: Prostate Cancer: Screening. U.S. Preventive Services Task Force. April 2016.
https://www.uspreventiveservicestaskforce.org/Page/Document/final-evidence-summary43/prostate-cancer-screening

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