The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up

Study Type – Prognosis (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Patients with biochemical recurrence after prostatectomy often develop subsequent metastases. However, the natural history of metastatic progression in men who have not received subsequent therapies before developing metastases has been understudied. Here, we describe the largest known cohort of men with PSA‐recurrent prostate cancer after prostatectomy who have not received additional treatments before metastasis. We characterize metastatic risk based on clinical variables, and we show that Gleason score and PSA doubling time are the strongest predictors of metastasis‐free survival. We present tables stratifying metastatic risk by these two variables.

OBJECTIVE

• ? To describe metastasis‐free survival (MFS) in men with prostate‐specific antigen (PSA) recurrence following radical prostatectomy, and to define clinical prognostic factors modifying metastatic risk.

PATIENTS AND METHODS

• ? We conducted a retrospective analysis of 450 men treated with prostatectomy at a tertiary hospital between July 1981 and July 2010 who developed PSA recurrence (≥0.2 ng/mL) and never received adjuvant or salvage therapy before the development of metastatic disease.
• ? We estimated MFS using the Kaplan–Meier method, and investigated factors influencing the risk of metastasis using Cox proportional hazards regression.

RESULTS

• ? Median follow‐up after prostatectomy was 8.0 years, and after biochemical recurrence was 4.0 years. At last follow‐up, 134 of 450 patients (29.8%) had developed metastases, while median MFS was 10.0 years.
• ? Using multivariable regressions, two variables emerged as independently predictive of MFS: PSA doubling time (<3.0 vs 3.0–8.9 vs 9.0–14.9 vs ≥15.0 months) and Gleason score (≤6 vs 7 vs 8–10).
• ? Using these stratifications of Gleason score and PSA doubling time, tables were constructed to predict median, 5‐ and 10‐year MFS after PSA recurrence. In different patient subsets, median MFS ranged from 1 to 15 years.

CONCLUSIONS

• ? In men undergoing prostatectomy, MFS after PSA recurrence is variable and is most strongly influenced by PSA doubling time and Gleason score. These parameters serve to stratify men into different risk groups with respect to metastatic progression.
• ? Our findings may provide the background for appropriate selection of patients, treatments and endpoints for clinical trials.

     

Prediction of outcomes after radical prostatectomy in patients diagnosed with prostate cancer of biopsy Gleason score ≥ 8 via contemporary multi (≥ 12)-core prostate biopsy

Study Type – Prognostic (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Currently, controversy continues with regards to the efficacy of performing radical prostatectomy (RP) and the potential predictor of outcome after surgery in patients with prostate cancers of higher biopsy Gleason score. Among contemporary patients with biopsy Gleason score ≥8 who underwent RP alone, patients with pathologically organ‐confined disease demonstrated significantly better biochemical outcome than others. Serum PSA level and maximum tumour length in a biopsy core, independent predictors of organ‐confined disease, would be useful in the selection of candidates for RP among patients presenting with biopsy Gleason score ≥8.

OBJECTIVE

• ? To investigate the outcome of patients who underwent radical prostatectomy (RP) for prostate cancer of biopsy Gleason score ≥ 8 diagnosed via contemporary prostate biopsy.

PATIENTS AND METHODS

• ? We reviewed records of 151 patients who underwent RP for prostate cancer of biopsy Gleason score ≥ 8 detected via multi (≥12)‐core prostate biopsy without any neoadjuvant or adjuvant treatment.
• ? Preoperative predictors of pathologically organ‐confined disease along with biochemical recurrence‐free survival were analyzed via multivariate logistic regression and Cox proportional hazards model.

RESULTS

• ? For 151 total subjects, 5‐year estimated biochemical recurrence‐free survival rate was 41.0%. Patients with pathologically organ‐confined disease were observed to have much higher 5‐year biochemical recurrence‐free survival rate than those otherwise (72.1 vs 31.5%, P < 0.001).
• ? Serum PSA level (P= 0.031) and maximum tumour length in a biopsy core (P= 0.005) were observed to be significant preoperative predictors of having pathologically organ‐confined disease.
• ? As for biochemical recurrence‐free survival following RP, serum PSA (P= 0.023), biopsy Gleason score (P= 0.032), and percent of total tumour length in biopsy cores (P < 0.001) were observed be significant preoperative predictors on multivariate analysis.

CONCLUSION

• ? Among contemporary patients with biopsy Gleason score ≥ 8 who underwent RP alone, patients with pathologically organ‐confined disease demonstrated significantly better biochemical outcome than others. Serum PSA level and maximum tumour length in a biopsy core, independent predictors of organ‐confined disease, would be useful in the selection of candidates for RP among patients presenting with biopsy Gleason score ≥ 8.

     

Evolution of the clinical presentation of men undergoing radical prostatectomy for high-risk prostate cancer

Study Type – Prognosis cohort series (multi‐centre) Level of Evidence 4 What's known on the subject? and What does the study add? Men with high‐risk prostate cancer experience recurrence, metastases and death at a higher rate in the prostate cancer population. This study adds greater than 20‐year data regarding the continued evolution of high‐risk prostate cancer toward high‐Gleason disease as the sole determinant of high‐risk status prior to radical prostatectomy. It validates the accumulation of multiple‐risk factors as a poor prognostic indicator in a radical prostatectomy population and demonstrates long‐term cancer specific outcomes, extending the findings demonstrated by previous publications.

OBJECTIVE

• ? To investigate the outcomes and potential effect of improved longitudinal screening in men presenting with high‐risk (advanced clinical stage [>T2b], Gleason score 8–10 or prostate‐specific antigen [PSA] level >20 ng/mL) prostate cancer (PC).

PATIENTS AND METHODS

• ? The Institutional Review Board approved, Institutional Radical Prostatectomy Database (1992–2010) was queried for men with high‐risk PC based on D'Amico criteria.
• ? Year of surgery was divided into two cohorts: the Early PSA Era (EPE, 1992–2000) and the Contemporary PSA Era (CPE, 2001–2010).
• ? PC features and outcomes were evaluated using appropriate comparative tests.

RESULTS

• ? In total, 667 men had high‐risk PC in the EPE and 764 in the CPE.
• ? In the EPE, 598 (89.7%) men presented with one high‐risk feature; 173 (29.0%) men had a Gleason score of 8–10 on biopsy. In the CPE, 717 (93.9%) men presented with one high‐risk feature (P= 0.004) and 494 (68.9%) men had a Gleason score of 8–10.
• ? At 10 years, biochemical‐free survival (BFS) was 44.1% and 36.4% in the EPE and CPE, respectively (P= 0.04); metastases‐free survival (MFS) was 77.1% and 85.1% (P= 0.6); and PC‐specific survival (CSS) was 83.3% and 96.2% (P= 0.5).
• ? BFS, MFS and CSS were worse for men with more than one high‐risk feature in both eras.

CONCLUSIONS

• ? Over the PSA era, an increasing percentage of men with high‐risk PC were categorized by a biopsy Gleason score of 8–10.
• ? The accumulation of multiple high‐risk features increases the risk of biochemical recurrence, the development of metastases and death from PC.
• ? BFS, MFS and CSS are stable over the PSA era for these men. The balance between a greater proportion of men having high Gleason disease and a greater proportion with small, less advanced tumours may explain the stability in MFS and CSS over time.

     

High Gleason grade carcinoma at a positive surgical margin predicts biochemical failure after radical prostatectomy and may guide adjuvant radiotherapy

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Only 30–35% of patients with positive surgical margins after radical prostatectomy develop recurrent disease. Adjuvant radiotherapy reduces the rate of biochemical relapse or metastasis and improves overall survival after radical prostatectomy. Various pathological factors, such as location and extent of positive margins, have been proposed as possible prognostic factors in men with margin‐positive prostate cancer, however, the recent International Society of Urological Pathology consensus meeting in Boston noted that there is limited data on the significance of Gleason grade of the carcinoma at a positive margin. The present study shows that the presence of high grade prostate cancer, i.e. Gleason pattern 4 or 5, at a positive surgical margin is an independent predictor of biochemical recurrence after radical prostatectomy. Moreover, patients with lower grade carcinoma at the margin have a similar prognosis to men with negative margins. Hence, assessment of Gleason grade at the site of positive margin may aid optimal selection of patients for adjuvant radiotherapy.

OBJECTIVE

• ? To establish predictors of biochemical recurrence by analysing the pathological characteristics of positive surgical margins (PSMs), including Gleason grade of the carcinoma at the involved margin.

PATIENTS AND METHODS

• ? Clinicopathological and outcome data on 940 patients who underwent radical prostatectomy (RP) between 1997 and 2003 were collected.
• ? Of these, 285 (30.3%) patients with PSMs were identified for pathological review, including assessment of location of margin, linear extent, number of PSMs, plane of margin and Gleason grade (3 vs 4 or 5) at the margin.

RESULTS

• ? At a median follow‐up of 82 months, the biochemical recurrence rate of the PSM cohort was 29%.
• ? On univariate analysis, the presence of Gleason grade 4 or 5 at the margin (34.4% of cases) was significantly associated with biochemical recurrence (hazard ratio [HR] 2.80, 95% confidence interval [CI]= 1.82–4.32, P < 0.001) compared with the presence of Gleason grade 3.
• ? Linear extent of margin involvement was also associated with recurrence (P= 0.009).
• ? Single vs multiple margin involvement, location, and plane of the involved margin were not significant predictors of recurrence.
• ? On multivariate analysis, Gleason grade 4 or 5 at the margin remained an independent predictor of recurrence (HR 2.14, 95% CI = 1.29–4.03, P= 0.003).

CONCLUSION

• ? The Gleason grade at the site of a PSM identifies patients at increased risk of biochemical recurrence and should aid stratification of patients for adjuvant radiation therapy.

     

Gleason 7 prostate cancer treated with low‐dose‐rate brachytherapy: lack of impact of primary Gleason pattern on biochemical failure

What's known on the subject? and What does the study add? There appears to be a clear difference in cancer control outcomes for patients with Gleason scores of 3+4 and those with scores of 4+3 after radical prostatectomy. It has been documented that patients with Gleason 4+3 prostate cancer have higher incidences of non‐organ‐confined disease than those with primary pattern 3. Higher rates of extracapsular extension, seminal vesicle invasion and positive margins have been found to be associated with primary pattern 4 over 3. These higher rates of non‐organ‐confined disease can lead to increased biochemical failure, which, in turn, can lead to higher mortality rates. This study provides information on the prognostic significance of primary Gleason pattern in the brachytherapy management of prostate cancer. Study Type – Prognosis (case series) Level of Evidence 4

OBJECTIVES

• ? To report the biochemical outcomes for Gleason 7 prostate cancer treated with brachytherapy.
• ? To analyse the impact of the primary Gleason pattern as well as other disease‐ and treatment‐related factors on outcome.

PATIENTS AND METHODS

• ? A total of 560 patients with Gleason 7 prostate cancer were treated between 1990 and 2008 with brachytherapy, alone or in combination with hormonal therapy and/or external beam radiation therapy.
• ? There were 352 patients with Gleason pattern 3+4 and 208 with Gleason pattern 4+3.
• ? The mean (range) presenting PSA level was 11.2 (1–300) ng/mL, and the median was 7.8 ng/mL.
• ? The presenting clinical stages were T1b in 1%, T1c in 33%, T2a in 16%, T2b in 32%, T2c in 16% and T3 in 2% of patients.

RESULTS

• ? The actuarial freedom from biochemical failure rate at 10 years was 82%.
• ? There was no significant difference between 10‐year freedom from biochemical failure rates for patients with Gleason scores of 3+4 (79%) and those with scores of 4+3 (82%).
• ? Biologically effective dose and presenting PSA level were both significant predictors of biochemical failure in multivariate analysis.

CONCLUSIONS

• ? The primary Gleason pattern in Gleason 7 prostate cancer shows no significant effect on biochemical failure when treated with brachytherapy.
• ? These results are different from those found after radical prostatectomy and are probably attributable to the enhanced local control afforded by a brachytherapy approach to this disease subset.

     

Impact of surgical margin status on prostate‐cancer‐specific mortality

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Surgical margin status at radical prostatectomy (RP) has been shown to be a predictor of disease progression and the strongest predictor of benefit from adjuvant therapy, but the impact of a positive surgical margin (PSM) on long‐term prostate‐cancer‐specific survival is unknown. The PSM rate is dependent on the pathological stage of the cancer. In a recent multicentre nomogram for 15‐year prostate‐cancer‐specific mortality (PCSM) after RP, PSM was not significantly associated with PCSM, while Gleason score and pathological stage were the only significant predictors. This has not been validated in a single centre, and PSM has been shown to vary greatly with surgical technique. This is the first study on the impact of PSM on PCSM in a single surgeon's cohort. In other centres, the decision to administer adjuvant therapy may be influenced by surgical margin status. In this cohort, men routinely did not receive adjuvant therapy, affording the unique opportunity to study the long‐term implications of a PSM.

OBJECTIVE

• ? To examine the relative impact of a positive surgical margin (PSM) and other clinicopathological variables on prostate‐cancer‐specific mortality (PCSM) in a large retrospective cohort of patients undergoing radical prostatectomy (RP).

PATIENTS AND METHODS

• ? Between 1982 and 2011, 4569 men underwent RP performed by a single surgeon.
• ? Of the patient population, 4461 (97.6%) met all the inclusion criteria.
• ? The median (range) age was 58 (33–75) years and the median prostate‐specific antigen (PSA) was 5.4 ng/mL; RP Gleason score was ≤6 in 2834 (63.7%), 7 in 1351 (30.3%), and 8–10 in 260 (6.0%) patients; PSMs were found in 462 (10.4%) patients.
• ? Cox proportional hazards models were used to determine the impact of a PSM on PCSM.

RESULTS

• ? At a median (range) follow‐up of 10 years (1–29), 187 men (4.3%) had died from prostate cancer.
• ? The 20‐year prostate‐cancer‐specific survival rate was 75% for those with a PSM and 93% for those without.
• ? Compared with those with a negative surgical margin, men with a PSM were more likely to be older (median age 60 vs 58 years) and to have undergone RP in the pre‐PSA era (36.6% vs 11.8%). Additionally, they were more likely to have a higher PSA level (median 7.6 vs 5.2 ng/mL), a Gleason score of ≥7 (58.7% vs 33.7%), and a non‐organ‐confined tumour (90.9% vs 30.6% [P < 0.001 for all]).
• ? In a univariate model for PCSM, PSM was highly significant (hazard ratio [HR] 5.0, 95% confidence interval [CI] 3.7–6.7, P < 0.001).
• ? In a multivariable model, adjusting for pathological variables and RP year, PSM remained an independent predictor of PCSM (HR 1.4, 95% CI 1.0–1.9, P= 0.036) with a modest effect relative to RP Gleason score (HR 5.7–12.6) and pathological stage (HR 2.2–11.0 [P < 0.001]).

CONCLUSION

• ? Although a PSM has a statistically significant adverse effect on prostate‐cancer‐specific survival in multivariable analysis, Gleason grade and pathological stage were stronger predictors.

     

A post‐radical‐prostatectomy nomogram incorporating new pathological variables and interaction terms for improved prognosis

Study Type – Prognosis (systematic review)
Level of Evidence 2a What’s known on the subject? and What does the study add? Nomograms are commonly used by urologists to assess a patient’s risk of developing biochemical failure (PSA recurrence) after radical prostatectomy. The nomograms currently available on websites and in the published literature do not take into account recent developments in pathological reporting which may improve our ability to more accurately predict patient prognosis. Furthermore, currently available nomograms treat all clinical predictors as independent variables without considering the possibility that these factors may be interlinked, which may alter their predictive value. Our study assesses the predictive value of several new pathological variables and demonstrates that the per cent of Gleason patterns 4 and/or 5 (% 4/5), intraductal prostatic carcinoma and prostate weight significantly improve the predictive value of a model based on established pathological variables. We also show that consideration of interactions between % 4/5, surgical margin status and extracapsular extension further improves our accuracy in predicting patient PSA recurrence. Finally, we find that published nomograms based on PSA recurrence defined as ≥0.4 ng/mL provide over‐optimistic predictions for prostate cancer patients where PSA recurrence was defined as ≥0.2 ng/mL.

OBJECTIVE

• ? To evaluate new variables in prostate pathology reporting including, the per cent of Gleason patterns 4 and/or 5 (% 4/5), presence or absence of intraductal carcinoma of the prostate (IDCP), tumour volume and the prostatic zone of tumour origin as predictors of post‐radical‐prostatectomy (RP) biochemical recurrence (BCR).
• ? To develop an optimal postoperative nomogram for patients with prostate cancer.

PATIENTS AND METHODS

• ? Our study cohort was 1939 eligible patients from the Abbott West Australian Prostatectomy Database.
• ? Multivariate Cox proportional hazard regression models were developed to predict BCR which was defined as prostate‐specific antigen (PSA) ≥0.2 ng/mL.
• ? Our models and the 2009 Kattan postoperative nomogram were compared in terms of discrimination and calibration, with internal validation of our final model performed using bootstrapping methods. Our final model is presented as a nomogram.

RESULTS

• ? The Kattan nomogram was accurate in discriminating our patients according to risk (concordance index: 0.791) but calibration analysis indicated underestimation of patient risk, particularly for high‐risk disease.
• ? Our nomogram incorporates % 4/5, IDCP and prostate weight plus interaction terms between % 4/5, positive surgical margins and extracapsular extension, giving improved predictive accuracy (concordance index: 0.828) and calibration.

CONCLUSIONS

• ? Nomograms that predict risk of BCR defined as PSA ≥0.4 ng/mL may not be optimal for patient cohorts where BCR is defined as PSA ≥0.2 ng/mL.
• ? If our findings are validated in other populations, current post‐RP nomograms may be improved to a modest degree by incorporating the new variables prostate weight, IDCP and % 4/5, and by considering interactions between predictive variables.

     

Biochemical outcome after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal. The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.

OBJECTIVE

• ? To investigate the long‐term oncological outcome, during the PSA era, of patients with prostate cancer who were treated using high‐dose‐rate (HDR) brachy therapy (BT) combined with external beam radiation therapy (EBRT).

PATIENTS AND METHODS

• ? From June 1998 to April 2007, 313 patients with localized prostate cancer were treated with 46 Gy of EBRT to the pelvis with a HDR‐BT boost.
• ? The mean (median) follow‐up was 71 (68) months.
• ? Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, V.4.

RESULTS

• ? The 10‐year actuarial biochemical control was 100% for patients with no high‐risk criteria, 88% for patients with two intermediate‐risk criteria, 91% with one high‐risk criterion and 79% for patients with two to three high‐risk criteria (P= 0.004).
• ? The 10‐year cancer‐specific survival was 97% (standard deviation ±1%).
• ? The multivariate Cox regression analyses identified, Gleason score and T stage as independent prognostic factors for biochemical failure.
• ? Gleason score was the only factor to significantly affect distant metastases.
• ? Grade ≥3 late toxicity was not detected.

CONCLUSION

• ? The 10‐year results confirm the feasibility and effectiveness of EBRT with conformal HDR‐BT boost for patients with localised prostate cancer.

     

Preoperative characteristics of high-Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Men with high‐risk prostate cancer experience recurrence, metastases and death at the highest rate in the prostate cancer population. Pathological stage at radical prostatectomy (RP) is the greatest predictor of recurrence and mortality in men with high‐grade disease. Preoperative models predicting outcome after RP are skewed by the large proportion of men with low‐ and intermediate‐risk features; there is a paucity of data about preoperative criteria to identify men with high‐grade cancer who may benefit from RP. The present study adds comprehensive biopsy data from a large cohort of men with high‐grade prostate cancer at biopsy. By adding biopsy parameters, e.g. number of high‐grade cores and >50% involvement of any core, to traditional predictors of outcome (prostate‐specific antigen concentration, clinical stage and Gleason sum), we can better inform men who present with high‐grade prostate cancer as to their risk of favourable or unfavourable disease at RP.

OBJECTIVE

• ? To investigate preoperative characteristics that distinguish favourable and unfavourable pathological and clinical outcomes in men with high biopsy Gleason sum (8–10) prostate cancer to better select men who will most benefit from radical prostatectomy (RP).

PATIENTS AND METHODS

• ? The Institutional Review Board‐approved institutional RP database (1982–2010) was analysed for men with high‐Gleason prostate cancer on biopsy; 842 men were identified.
• ? The 10‐year biochemical‐free (BFS), metastasis‐free (MFS) and prostate cancer‐specific survival (CSS) were calculated using the Kaplan–Meier method to verify favourable pathology as men with Gleason <8 at RP or ≤ pT3a compared with men with unfavourable pathology with Gleason 8–10 and pT3b or N1.
• ? Preoperative characteristics were compared using appropriate comparative tests.
• ? Logistic regression determined preoperative predictors of unfavourable pathology.

RESULTS

• ? There was favourable pathology in 656 (77.9%) men. The 10‐year BFS, MFS and CSS were 31.0%, 60.9% and 74.8%, respectively.
• ? In contrast, men with unfavourable pathological findings had significantly worse 10‐year BFS, MFS and CSS, at 4.3%, 29.1% and 52.3%, respectively (all P < 0.001).
• ? In multivariable logistic regression, a prostate‐specific antigen (PSA) concentration of >10 ng/mL (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.38–3.62, P= 0.001), advanced clinical stage (≥ cT2b; OR 2.55, 95% CI 1.55–4.21, P < 0.001), Gleason pattern 9 or 10 at biopsy (OR 2.55, 95% CI 1.59–4.09, P < 0.001), increasing number of cores positive with high‐grade cancer (OR 1.16, 95% CI 1.01–1.34, P= 0.04) and >50% positive core involvement (OR 2.25, 95% CI 1.17–4.35, P= 0.015) were predictive of unfavourable pathology.

CONCLUSIONS

• ? Men with high‐Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis.
• ? Among men with high‐Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical stage ≥ T2b, Gleason pattern 9 or 10, increasing number of cores with high‐grade cancer and >50% core involvement are predictive of unfavourable pathology.

     

Outcomes of initially expectantly managed patients with low or intermediate risk screen‐detected localized prostate cancer

Study Type – Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Active surveillance aims to reduce overtreatment by selecting patients with low risk prostate cancer (PCa) based on favourable disease characteristics. However, most studies on active surveillance do not have long‐term results available; in particular, data on patients with intermediate risk disease are lacking. Our findings demonstrate that withholding radical treatment in men with low or intermediate risk screen‐detected localized PCa leads to a substantial delay or even avoidance of radical treatment in a majority of men. Favourable disease‐specific outcomes confirm the feasibility of active surveillance for low risk PCa and also support a role for active surveillance in selected patients with intermediate risk PCa.

OBJECTIVE

• ? To assess the longer‐term feasibility of active surveillance, we aimed to evaluate outcomes of patients with screen‐detected localized prostate cancer (PCa) who initially elected to withhold radical treatment for either low or intermediate risk disease.

PATIENTS AND METHODS

• ? All men underwent screening for PCa in the Rotterdam and Helsinki arms of the European Randomized Study of Screening for Prostate Cancer (ERSPC); eligible men were diagnosed with PCa prior to the establishment of the ERSPC‐affiliated Prostate Cancer Research International: Active Surveillance (PRIAS) study (1994–2007) and were initially expectantly managed in the absence of a fixed follow‐up protocol.
• ? Low risk PCa was defined as clinical stage T1/T2, PSA ≤ 10 ng/mL, PSA density < 0.2 ng/mL/mL, Gleason ≤ 6 and maximum two positive biopsy cores, whereas PSA 10–20 ng/mL, Gleason score 7 and three positive biopsy cores were considered intermediate risk features.
• ? Disease‐specific, overall and treatment‐free survival were analysed using the Kaplan–Meier and competing risks methods.

RESULTS

• ? In all, 509 patients with PCa were eligible, of whom 381 were considered low risk and 128 intermediate risk.
• ? During a median follow‐up of 7.4 years, a total of 221 patients (43.4%) switched to deferred treatment after a median of 2.6 years.
• ? The calculated 10‐year disease‐specific survival rates were 99.1% and 96.1% for low and intermediate risk patients, respectively (P= 0.44), and for overall survival 79.0% and 64.5%, respectively (P= 0.003).
• ? Competing risks analysis showed similar results.

CONCLUSIONS

• ? Withholding radical treatment in men with low to intermediate risk screen‐detected PCa leads to a substantial delay or even avoidance of radical treatment and its potential side‐effects in a majority of patients.
• ? Disease‐specific outcomes at 7.4 years of follow‐up are favourable in low as well as intermediate risk patients.
• ? This confirms the feasibility of active surveillance according to contemporary criteria, and also suggests a potential role for active surveillance in selected men with intermediate risk features.

     

Magnetic resonance imaging does not improve the prediction of misclassification of prostate cancer patients eligible for active surveillance when the most stringent selection criteria are based on the saturation biopsy scheme

Study Type – Diagnostic (case series) Level of Evidence 4

OBJECTIVE

• ? To investigate the role of magnetic resonance imaging (MRI) in selecting patients for active surveillance (AS).

PATIENTS AND METHODS

• ? We identified prostate cancers patients who had undergone a 21‐core biopsy scheme and fulfilled the criteria as follows: prostate‐specific antigen (PSA) level ≤10 ng/mL, T1–T2a disease, a Gleason score ≤6, <3 positive cores and tumour length per core <3 mm.
• ? We included 96 patients who underwent a radical prostatectomy (RP) and a prostate MRI before surgery.
• ? The main end point of the study was the unfavourable disease features at RP, with or without the use of MRI as AS inclusion criterion.

RESULTS

• ? Mean age and mean PSA were 62.4 years and 6.1 ng/mL, respectively. Prostate cancer was staged pT3 in 17.7% of cases.
• ? The rate of unfavourable disease (pT3–4 and/or Gleason score ≥4 + 3) was 24.0%. A T3 disease on MRI was noted in 28 men (29.2%).
• ? MRI was not a significant predictor of pT3 disease in RP specimens (P = 0.980), rate of unfavourable disease (P = 0.604), positive surgical margins (P = 0.750) or Gleason upgrading (P = 0.314).
• ? In a logistic regression model, no preoperative parameter was an independent predictor of unfavourable disease in the RP specimen.
• ? After a mean follow‐up of 29 months, the recurrence‐free survival (RFS) was statistically equivalent between men with T3 on MRI and those with T1–T2 disease (P = 0.853).

CONCLUSION

• ? The results of the present study emphasize that, when the selection of patients for AS is based on an extended 21‐core biopsy scheme, and uses the most stringent inclusion criteria, MRI does not improve the prediction of high‐risk and/or non organ‐confined disease in a RP specimen.

     

General application of the National Institute for Health and Clinical Excellence (NICE) guidance for active surveillance for men with prostate cancer is not appropriate in unscreened populations

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance (AS) is a well‐recognised management strategy to minimise the morbidity associated with radical treatment of prostate cancer. The National Institute for Health and Clinical Excellence guidelines initially suggested that all men with low‐risk prostate cancer should first be offered AS. The cohort of men with upstaging and upgrading of prostate cancer from diagnosis to final pathology has been described in North American and European populations. As the rate of PSA testing in Britain is lower than North America and parts of Europe, the risk of more advanced disease at diagnosis of prostate cancer is higher. The present study is one of the first to examine this cohort in a British population and found the rate of features of advanced disease (extracapsular extension, seminal vesicle involvement and Gleason 4 + 3, or 8–10) to be 37.2%.

OBJECTIVE

• ? To determine if the National Institute for Health and Clinical Excellence (NICE) guidelines for men with low‐risk prostate cancer were generally applicable in unscreened populations.

PATIENTS AND METHODS

• ? Retrospective analysis of prospectively collected case series from a single tertiary care centre in England.
• ? In all, 700 consecutive men treated for prostate cancer from 2005 by robot‐assisted laparoscopic prostatectomy (RALP) were included.
• ? Patients satisfying NICE criteria for low‐risk disease (PSA level < 10 ng/mL and Gleason score ≤ 6 and cT1–2a) had their pathological samples analysed for advanced disease, defined as extracapsular extension (ECE: pT3), seminal vesicle involvement (SVI), Gleason sum 7, or 8–10 or node‐positive disease.

RESULTS

• ? In all, 275 patients (39.2%) met the NICE low‐risk criteria, but pathologically advanced disease was found in 37.2% of this group.
• ? There was ECE in 71 patients (25.8%), 10 had SVI (3.6%), nine (3.3%) had Gleason score 7 (4 + 3), and 12 had Gleason sum 8–10 (4.4%).

CONCLUSIONS

• ? The NICE guidance was developed largely on data from North America where populations are highly screened using PSA testing. In the UK, many men with low‐risk disease features have high‐risk disease and the general applicability of the NICE guidance is questionable in unscreened populations.
• ? We recommend that radical therapy is discussed as an alternative option to active surveillance.

     

Outcomes in patients with Gleason score 8-10 prostate cancer: relation to preoperative PSA level

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? High‐grade prostate cancers are associated with poor disease‐specific outcomes. A proportion of these tumours produce little PSA. This study demonstrates that among Gleason 8–10 prostate cancers, some of the worst survival outcomes are associated with the lowest PSA levels.

OBJECTIVE

• ? To assess outcomes of patients with Gleason score 8–10 prostate cancer (CaP) with a low (≤2.5 ng/mL) vs higher preoperative serum PSA levels.

PATIENTS AND METHODS

• ? From 1983 to 2003, 5544 patients underwent open radical prostatectomy, of whom 354 had a Gleason 8–10 tumour in the prostatectomy specimen.
• ? Patients were stratified according to preoperative PSA level into four strata: ≤2.5 ng/mL (n= 31), 2.6–4 ng/mL (n= 31), 4.1–10 ng/mL (n= 174), and >10 ng/mL (n= 118).
• ? We compared biochemical progression‐free survival (PFS), metastasis‐free survival (MFS), and cancer‐specific survival (CSS) as a function of preoperative PSA level.

RESULTS

• ? Patients with PSA level ≤2.5 ng/mL were more likely to have seminal vesicle invasion (P= 0.003).
• ? On Kaplan–Meier survival analysis, patients with a PSA level ≤2.5 ng/mL had proportionately worse outcomes than their counterparts with higher PSA levels.
• ? The 7‐year PFS in the PSA ≤2.5 ng/mL stratum was lower than those of the PSA 2.6–4 ng/mL and 4–10 ng/mL strata (36% vs 50 and 42%, respectively); however, the lowest 7‐year PFS was found in those with a PSA level >10 ng/mL (32%, P= 0.02).
• ? Gleason score 8–10 tumours with a PSA level ≤2.5 ng/mL also tended to have the lowest 7‐year MFS (75, 93, 89 and 92% for PSA level ≤2.5, 2.6–4, 4.1–10 and >10 ng/mL, respectively, P= 0.2) and CSS (81, 100, 94 and 90% for PSA level ≤2.5, 2.6–4, 4.1–10 and >10 ng/mL, respectively, P= 0.3), although these differences were not statistically significant.
• ? In the subset with palpable disease, Gleason grade 8–10 disease with PSA level ≤2.5 ng/mL also was associated with a worse prognosis.

CONCLUSIONS

• ? In patients with Gleason grade 8–10 disease, a proportion of these tumours are so poorly differentiated that they produce relatively little PSA.
• ? Patients with high‐grade, low‐PSA tumours had less favourable outcomes than many of those with higher PSA levels.

     

The ability of prostate-specific antigen (PSA) density to predict an upgrade in Gleason score between initial prostate biopsy and prostatectomy diminishes with increasing tumour grade due to reduced PSA secretion per unit tumour volume

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Due to sampling error, the Gleason score of clinically localized prostate cancer is frequently underestimated at the time of initial biopsy. Given that this may lead to inappropriate surveillance of patients with high‐risk disease, there is considerable interest in identifying predictors of significant undergrading. Recently PSAD has been proposed to be an accurate predictor of subsequent upgrading in patients diagnosed with Gleason 6 disease on biopsy. We examined the predictive characteristics of PSAD in patients with low‐ and intermediate‐risk disease on biopsy subsequently treated with radical prostatectomy. We found that although PSAD was a significant predictor of upgrade of biopsy Gleason 6 and 3 + 4 = 7 tumours, it failed to predict upgrading in patients with Gleason 7 tumours taken as a whole. When we explored reasons for this discrepancy, we found that the amount of PSA produced per unit tumour volume decreased with increasing Gleason score, thereby diminishing the predictive value of PSAD.

OBJECTIVES

• ? To analyse the performance of PSA density (PSAD) as a predictor of Gleason score upgrade in a large cohort stratified by Gleason score.
• ? We and others have shown that an upgrade in Gleason score between initial prostate biopsy and final radical prostatectomy (RP) pathology is a significant risk factor for recurrence after local therapy.

PATIENTS AND METHODS

• ? Patients undergoing RP with matching biopsy information were identified from two prospective databases.
• ? Patients were analysed according to the concordance between biopsy and final pathology Gleason score in three paired groups: 6/>6, 3 + 4/>3 + 4, 7/>7.
• ? Receiver‐operating characteristic (ROC) curves were generated stratified by Gleason score, and the area under the curve (AUC) calculated.
• ? Logistic regression models were fitted to identify significant predictors of tumour upgrade.

RESULTS

• ? From 1516 patients, 435 (29%) had an upgrade in Gleason score. ROC analysis showed a decline in AUC with increasing biopsy Gleason score, from 0.64 for biopsy Gleason score 6, to 0.57 for Gleason score 7.
• ? In logistic regression models containing pretreatment variables, e.g. clinical stage and number of positive cores, for Gleason score 6 and 3 + 4, PSAD was the strongest predictor of subsequent tumour upgrade (odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.18–1.83, P= 0.001 and OR 1.37, 95% CI 1.14–1.67, P= 0.002, respectively).
• ? Surprisingly, in tumours upgraded from Gleason score 7 to >7, PSAD was not predictive even on univariable analysis, whereas clinical stage and number of positive cores were significant independent predictors. To explore the relationship between serum PSA and Gleason score, tumour volume was calculated in 669 patients.
• ? There was a strong association between Gleason score and tumour volume, with the median volume of Gleason score 7 and Gleason score >7 tumours being approximately twice and four‐times that of Gleason score 6 tumours, respectively (P < 0.001).
• ? In contrast, the median serum PSA level per millilitre tumour volume decreased significantly with increasing grade, from 5.4 ng/mL for Gleason score 6 to 2.1 ng/mL for >7 (P < 0.001).

CONCLUSIONS

• ? There is a strong correlation between Gleason score and tumour volume in well/intermediate differentiated tumours, and as they produce relatively high amounts of PSA per unit volume of cancer, high PSAD is the strongest single predictor of tumour undergrading.
• ? However, as higher grade tumours produce less PSA per unit volume, PSAD loses its predictive ability, and other clinical markers of tumour volume such as palpable disease and numbers of positive cores become more predictive.

     

The extent of pelvic lymph node dissection correlates with the biochemical recurrence rate in patients with intermediate- and high-risk prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Pelvic lymph‐node dissection during radical prostatectomy for prostate cancer is certainly a fundamental staging procedure but its therapeutic role is yet under debate. This retrospective study suggests that, in patients with intermediate‐ and high‐risk of prostate cancer, the greater the number of lymph‐nodes removed, the lower the risk of biochemical relapse, even in the presence of 1 or 2 lymph‐node metastasis. However, the Will Rogers phenomenon must be considered due to the retrospective nature of the present study.

OBJECTIVE

• ? To assess the impact of pelvic lymph node dissection (PLND) and of the number of lymph nodes (LNs) retrieved during radical prostatectomy (RP) on biochemical relapse (BCR) in pNX/0/1 patients with prostate cancer according to the clinical risk of lymph node invasion (LNI).

PATIENTS AND METHODS

• ? We evaluated 872 pT2‐4 NX/0/1 consecutive patients submitted to RP between October 1995 and June 2009, with the following inclusion criteria: (i) a follow‐up period ≥12 months; (ii) the avoidance of neoadjuvant hormonal therapy or adjuvant hormonal and/or adjuvant radiotherapy; (iii) the availability of complete follow‐up data; (iv) no pathological T0 disease; (v) complete data regarding the clinical stage and Gleason score (Gs), the preoperative prostate‐specific antigen (PSA) level and the pathological stage.
• ? The patients were stratified as having low risk (cT1a‐T2a and cGs ≤6 and PSA level < 10 ng/mL), intermediate risk (cT2b‐T2c or cGs = 7 or PSA level = 10–19.9) or high risk of LNI (cT3 or cGs = 8–10 or PSA level ≥ 20).
• ? The 872 patients were divided into two LN groups according to the number of LNs retrieved: group 1 had no LN or one to nine LNs removed; group 2 had 10 or more LNs.
• ? The variables analysed were LN group, age, PSA level, clinical and pathological stage and Gs, surgical margin status, LN status and number of LN metastases; the primary endpoint was the BCR‐free survival.

RESULTS

• ? The mean follow‐up was 55.8 months.
• ? Of all the patients, 305 (35%) were pNx and 567 (65.0%) were pN0/1.
• ? Of the 567 patients submitted to PLND, the mean number of LNs obtained was 10.9, and 49 (8.6%) were pN1.
• ? In the 402 patients at low risk of LNI, LN group was not a significant predictor of BCR at univariate analysis, while in the 470 patients at intermediate and high risk of LNI, patients with ≥10 LNs removed had a significantly lower BCR‐free survival at univariate and multivariate analysis.

CONCLUSION

• ? In our study population, a more extensive PLND positively affects the BCR‐free survival regardless of the nodal status in intermediate‐ and high‐risk prostate cancer.

     

Single application of high‐intensity focused ultrasound as a first‐line therapy for clinically localized prostate cancer: 5‐year outcomes

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? High‐intensity focused ultrasound (HIFU) therapy has been proposed for the treatment of localized prostate cancer (PCa) for all risk levels of tumour recurrence. The study adds data on the efficacy of a single HIFU application in the treatment of PCa with different risks of recurrence. Durable cancer control was achieved in 81.7% of patients with low‐risk disease, with rates of efficacy declining in intermediate‐ and high‐risk tumours. The data suggest that the principal domain for minimal invasive HIFU should be low‐risk disease.

OBJECTIVE

• ? To report cancer control results after a single application of high‐intensity focused ultrasonography (HIFU) in patients with localized prostate cancer (PCa), stratified by tumour recurrence risk according to D'Amico risk classification.

PATIENTS AND METHODS

• ? In a retrospective single‐centre study, we analysed the outcomes of patients with localized PCa who were treated with curative intent between December 2002 and October 2006 using an Ablatherm HIFU device (EDAP‐TMS, France).
• ? Transurethral resection of the prostate or adenomectomy were performed before HIFU to downsize large prostate glands.
• ? Oncological failure was determined by the occurrence of biochemical relapse, positive biopsy and/or metastasis. Biochemical relapse was defined as a PSA nadir +1.2 ng/mL (Stuttgart definition), or as a rise in PSA level to ≥0.5 ng/mL if PSA doubling time was ≤6 months. Kaplan–Meier analysis was performed for survival estimates.

RESULTS

• ? A total of 191 consecutive patients were included in the study. The median (range) patient age was 69.7 (51–82) years, and 38, 34 and 28% of these patients were in the low‐, intermediate‐ and high‐risk groups, respectively.
• ? The median (range) follow‐up was 52.8 (0.2–79.8) months.
• ? At 5 years, overall and cancer‐specific survival rates were 86.3% and 98.4%, respectively.
• ? Stratified by risk group, negative biopsy rates were 84.2%, 63.6%, and 67.5% (P = 0.032), 5‐year biochemical‐free survival rates were 84.8%, 64.9% and 54.9% (P < 0.01), and 5‐year disease‐free survival rates were 81.7%, 53.2% and 51.2% (P < 0.01), respectively.

CONCLUSION

• ? Single‐session HIFU is recommended as a curative approach in elderly patients with low‐risk PCa. Patients at higher risk of tumour progression should be counselled regarding the likely need for salvage therapy, including repeat HIFU.

     

Prostate-specific antigen velocity (PSAV) risk count improves the specificity of screening for clinically significant prostate cancer

Study Type – Prognosis (retrospective cohort analysis) Level of Evidence 2b What's known on the subject? and What does the study add? PSA screening reduces prostate cancer mortality but also may lead to unnecessary biopsies and overdiagnosis of insignificant tumours. PSA velocity (PSAV) risk count (number of serial PSAV exceeding 0.4 ng/ml/year) significantly improves the performance characteristics of screening for overall prostate cancer and high‐grade disease on biopsy. Risk count may be useful to reduce unnecessary biopsies and prostate cancer overdiagnosis compared to PSA alone.

OBJECTIVE

• ? To determine whether the prostate‐specific antigen velocity (PSAV) risk count (i.e. the number of times PSAV exceeds a specific threshold) could increase the specificity of screening for prostate cancer and potentially life‐threatening tumours.

PATIENTS AND METHODS

• ? From 1989 to 2001, we calculated two serial PSAV measurements in 18 214 prostate cancer screening‐study participants, of whom 1125 (6.2%) were diagnosed with prostate cancer.
• ? The PSAV risk count was determined as the number of PSAV measurements of >0.4 ng/mL/year (0, 1, or 2).
• ? We used receiver operating characteristic (ROC) and reclassification analyses to examine the ability of PSAV risk count to predict screen‐detected and high‐grade prostate cancer.

RESULTS

• ? The PSAV was >0.4 ng/mL/year twice (risk count 2) in 40% of prostate cancer cases compared with only 4% of those with no cancer (P < 0.001).
• ? After adjusting for age and PSA level, a PSAV risk count of 2 was associated with an 8.2‐fold increased risk of prostate cancer (95% confidence interval 7.0–9.6, P < 0.001) and 5.4‐fold increased risk of Gleason score 8–10 prostate cancer on biopsy.
• ? Compared with a model with age and PSA level, the addition of the PSAV risk count significantly improved discrimination (area under the ROC curve 0.625 vs 0.725, P= 0.031) and reclassified individuals for the risk of high‐grade prostate cancer (net reclassification, P < 0.001).

CONCLUSIONS

• ? Sustained rises in PSA indicate a significantly greater risk of prostate cancer, particularly high‐grade disease.
• ? Compared with men with a risk count of ≤1, those with two PSAV measurements of >0.4 ng/mL/year (risk count 2) had an 8‐fold increased risk of prostate cancer and 5.4‐fold increased risk of Gleason 8–10 disease on biopsy, adjusting for age and PSA level.
• ? Compared to PSA alone, PSAV risk count may be useful in reducing unnecessary biopsies and the diagnosis of low‐risk prostate cancer.

     

Patients aged more than 70 had higher risk of locally advanced prostate cancers and biochemical recurrence in Korea

Study Type – Prognosis (cohort series) Level of Evidence 2b What's known on the subject? and What does the study add? This study reports that patients aged 70 years or older have a higher possibility of locally advanced cancer than younger patients. Instead of conservative management, radical eradication of clinically localized prostate cancer should be actively considered in well‐selected healthy patients older than 70 years.

OBJECTIVE

• ? To analyse the differences in the clinicopathological results between two groups of Korean patients aged younger or older than 70 years with clinically localized prostate cancer.

METHODS

• ? A cohort of consecutive male patients who underwent radical prostatectomy was retrospectively analysed. In total, 995 patients (74.6%) were younger than 70 years, and 338 patients (25.4%) were 70 years or older.
• ? Biochemical recurrence (BCR) ‐free survival was evaluated in the patients, who were followed up for more than 24 months.
• ? The Kaplan–Meier method was used to calculate survival estimates for BCR‐free survival. Multivariate Cox proportional hazard regression analysis was performed to predict non‐organ‐confined status and BCR.

RESULTS

• ? Mean preoperative prostate‐specific antigen (PSA) levels and biopsy or pathological Gleason scores showed no differences between the two age groups.
• ? Older patients, aged more than 70 years, displayed significantly higher risk of locally advanced prostate cancer and BCR than younger patients.
• ? Subgroup analysis showed that the risk of the presence of locally advanced disease was significantly increased in patients of 70 years or older when we compared the proportion of locally advanced disease only in patients with PSA <4 ng/mL.
• ? Multivariate analysis showed that old age, high PSA and high Gleason score were significantly associated with non‐organ confined status and BCR.

CONCLUSIONS

• ? Patients aged 70 years or older had a higher possibility of locally advanced cancer than younger patients.
• ? Radical eradication of clinically localized prostate cancer should be actively considered in well‐selected healthy patients older than 70 years.

     

Low pretreatment total testosterone (< 3 ng/mL) predicts extraprostatic disease in prostatectomy specimens from patients with preoperative localized prostate cancer

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

• ? To investigate the relationship between pretreatment testosterone levels and pathological specimen characteristics, by prospectively examining serum androgen concentrations in a well‐studied cohort of patients who underwent radical prostatectomy (RP) for localized prostate cancer.

PATIENTS AND METHODS

• ? A total of 107 patients with clinically localized prostate cancer had an assay of total testosterone before laparoscopic RP at our institution.
• ? The results were classified into two groups based on the total serum testosterone: group1, <3 ng/mL; group 2, ≥3 ng/mL.
• ? Student’s t‐test was used to compare continuous variables, and Fisher’s exact test or the chi‐squared test was used to compare categorical variables.
• ? Survival curves were established using the Kaplan–Meier method and compared using the log‐rank test. In all tests, P < 0.05 was considered to indicate statistical significance.

RESULTS

• ? All patients had localized prostate cancer based on digital rectal examination (DRE) and preoperative magnetic resonance imaging (MRI). Groups 1 and 2 were similar in terms of age, body mass index, preoperative co‐morbidities (cardiovascular and diabetes mellitus), clinical stage of prostate cancer and preoperative PSA levels.
• ? In pathological specimens, low total testosterone (<3 ng/mL) was an independent risk factor for high Gleason score (>7) and for locally advanced pathological stage (pT3 and pT4).
• ? Higher preoperative testosterone correlated with disease confined to the gland.
• ? There was no association between serum testosterone levels and surgical margin status, on the one hand, and biochemical recurrence on the other.

CONCLUSION

• ? Low serum testosterone appears to be predictive of aggressive disease (Gleason score >7 and extraprostatic disease, pathological stage >pT2) in patients who underwent RP for localized prostate cancer.

     

The short-term use of erythropoetin-stimulating agents: impact on the biochemical recurrence of prostate cancer

Study Type – Harm (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Erythropoletin‐stimulating agents (ESAs) have been widely prescribed for treating anaemia secondary to advanced maligancies with the objective of reducing the need for red blood cell transfusions and improving the quality of life. However, the risk/benefit of ESAs has recently been questioned and metaanalyses showing that these agents are associated with an increased risk of mortality when chronically administered to patients with advanced/metastatic cancers. In this study we examined the impact of short‐term preoperative utilization of ESAs on biochemical recurrence – free survival rates after open radical retropubic prostatectomy (ORRP).

OBJECTIVE

• ? To examine the impact of short‐term preoperative utilization of erythropoietin‐stimulating agents (ESAs) on biochemical recurrence (BCR)‐free survival rates after open radical retropubic prostatectomy (ORRP) in light of the fact that the risk/benefit of ESAs has recently been questioned by the Food and Drug Administration (FDA) after reports showing a decreased survival.

PATIENTS AND METHODS

• ? From 2000 to 2008, 1567 patients underwent ORRP and 97.5% of these signed informed consent to participate in the New York University Prospective and Longitudinal Outcomes Study.
• ? Of the remaining 1528 patients, 1317 (86%) received preoperative ESA (group 1) and 211 (14%) did not (group 2).
• ? Patients were also classified as having low‐, intermediate‐ or high‐risk disease based on D’Amico risk categories.
• ? Kaplan–Meier survival curves and Cox’s proportional hazard models were used to estimate BCR‐free survival by ESA treatment.

RESULTS

• ? A significant difference was observed for BCR‐free survival between the low‐ and intermediate/high‐risk groups.
• ? There were no statistically significant differences between groups 1 and 2 for BCR‐free survival in the entire study populations and within risk groups.
• ? In addition, Cox regression models showed no statistically significant differences in BCR‐free survival according to preoperative ESA administration in the entire cohort as well as among the low‐ and intermediate/high‐risk groups.

CONCLUSIONS

• ? The short‐term use of ESAs as a preoperative blood management strategy for patients undergoing ORRP has no clinically relevant adverse effects on the biology of prostate cancer.
• ? The present study supports the use of these agents before the procedure in patients undergoing surgery for localized disease.