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.

     

Advancing age within established Gleason score categories and the risk of prostate cancer-specific mortality (PCSM)

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? There is limited data that suggests that men aged >70 years have a higher proportion of Gleason 8–10 prostate cancer than men aged <70 years, as well as a higher risk of PSA recurrence, distant metastases, and disease‐specific death on univariate analysis. The present study shows that older as compared with younger men with Gleason score 6 and 7 prostate cancer have an increased risk of prostate cancer‐specific mortality. This may be due to the presence of occult high‐grade disease and suggests further diagnostic studies, e.g. multiparametric MRI, may be indicated in these men to reduce biopsy sampling error.

OBJECTIVE

• ? To determine if advancing age is a risk factor for high‐grade prostate cancer due to occult high‐grade disease in elderly men with Gleason score 6 or 7 prostate cancer. We investigated whether advancing age is associated with the risk of prostate cancer‐specific mortality (PCSM) within established Gleason score categories adjusting for known predictors of PCSM.

PATIENTS AND METHODS

• ? Using data from the Surveillance, Epidemiology and End Results database between 1 January 2004 to 31 December 2007, 166 104 men with non‐metastatic prostate cancer were identified and formed the study cohort.
• ? Within established Gleason score categories, Fine and Gray's multivariable competing risk regressions were used to evaluate whether increasing age at diagnosis was significantly associated with an increased risk of PCSM, adjusting for prostate‐specific antigen level and T‐category at diagnosis and whether treatment was curative or non‐curative.

RESULTS

• ? After adjusting for treatment and prognostic factors, Gleason score 8–10 and 7 as compared with ≤6 was associated with an increased risk of PCSM (P < 0.001).
• ? Increasing age was associated with an increased risk of PCSM only in Gleason score 6 (adjusted hazard ratio [AHR] 1.06, 95% confidence interval [CI] 1.04–1.08, P < 0.001) and 7 (AHR 1.02, 95% CI 1.01–1.03, P < 0.001), but not with Gleason score 8–10 (AHR 0.999, 95% CI 0.995–1.003, P= 0.61).
• ? These risks were highest in men aged >70 years having Gleason score 6 (AHR 1.10, 95% CI 1.07–1.13, P < 0.001) and Gleason score 7 prostate cancer (AHR 1.04, 95% CI 1.02–1.06, P < 0.001).

CONCLUSIONS

• ? PCSM increases with advancing age in men with Gleason score 6 and 7 but not 8–10 prostate cancer.
• ? Techniques to reduce biopsy sampling error in men, particularly those aged >70 years and healthy with Gleason score 6 and 7 disease deserve further study.

     

Radical prostatectomy vs radiation therapy and androgen-suppression therapy in high-risk prostate cancer

Study Type – Therapy (retrospective cohort analysis) Level of Evidence 2b What's known on the subject? and What does the study add? Prostate cancer is generally considered to be high risk when the prostate‐specific antigen (PSA) concentration is >20 ng/mL, the Gleason score is ≥8 or the American Joint Commission on Cancer (AJCC) tumour (T) category is ≥2c. There is no consensus on the best treatment for men with prostate cancer that includes these high‐risk features. Options include external beam radiation therapy (EBRT) with androgen suppression therapy (AST), treatment with a combination of brachytherapy, EBRT and AST termed combined‐modality therapy (CMT) or radical prostatectomy (RP) followed by adjuvant RT in cases where there are unfavourable pathological features, e.g. positive surgical margin, extracapsular extension and seminal vesicle invasion. While outcomes for both approaches have been published independently these treatments have not been compared in the setting of a prospective RCT where confounding factors related to patient selection for RP or CMT would be minimised. These factors include age, known prostate cancer prognostic factors and comorbidity. RCTs that compare RP to radiation‐based regimens have been attempted but failed to accrue.

OBJECTIVE

• ? To assess the risk of prostate cancer‐specific mortality after therapy with radical prostatectomy (RP) or combined‐modality therapy (CMT) with brachytherapy, external beam radiation therapy (EBRT) and androgen‐suppression therapy (AST) in men with Gleason score 8–10 prostate cancer.

PATIENTS AND METHODS

• ? Men with localised high‐risk prostate cancer based on a Gleason score of 8–10 were selected for study from Duke University (285 men), treated between January 1988 and October 2008 with RP or from the Chicago Prostate Cancer Center or within the 21st Century Oncology establishment (372) treated between August 1991 and November 2005 with CMT.
• ? Fine and Gray multivariable regression was used to assess whether the risk of prostate cancer‐specific mortality differed after RP as compared with CMT adjusting for age, cardiac comorbidity and year of treatment, and known prostate cancer prognostic factors.

RESULTS

• ? As of January 2009, with a median (interquartile range) follow‐up of 4.62 (2.4–8.2) years, there were 21 prostate cancer‐specific deaths.
• ? Treatment with RP was not associated with an increased risk of prostate cancer‐specific mortality compared with CMT (adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6–5.6, P= 0.3).
• ? Factors associated with an increased risk of prostate cancer‐specific mortality were a PSA concentration of <4 ng/mL (adjusted HR 6.1, 95% CI 2.3–16, P < 0.001) as compared with ≥4 ng/mL, and clinical category T2b, c (adjusted HR 2.9; 95% CI 1.1–7.2; P= 0.03) as compared with T1c, 2a.

CONCLUSION

• ? Initial treatment with RP as compared with CMT was not associated with an increased risk of prostate cancer‐specific mortality in men with Gleason score 8–10 prostate cancer.

     

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.

     

Long‐term radical prostatectomy outcomes among participants from the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Radical prostatectomy was previously shown to improve long‐term outcomes among men with clinically‐detected prostate cancer. Our data suggests that radical prostatectomy is also associated with improved outcomes in men with screen‐detected prostate cancer.

OBJECTIVE

• ? To examine the long‐term outcomes of radical prostatectomy (RP) among men diagnosed with prostate cancer from the screening and control arms of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC).

PATIENTS AND METHODS

• ? Among 42 376 men randomised during the period of the first round of the trial (1993–1999), 1151 and 210 in the screening and control arms were diagnosed with prostate cancer, respectively.
• ? Of these men, 420 (36.5%) screen‐detected and 54 (25.7%) controls underwent RP with long‐term follow‐up data (median follow‐up 9.9 years).
• ? Progression‐free (PFS), metastasis‐free (MFS) and cancer‐specific survival (CSS) rates were examined, and multivariable Cox proportional hazards models were used to determine whether screen‐detected (vs control) was associated with RP outcomes after adjusting for standard predictors.

RESULTS

• ? RP cases from the screening and control arms had statistically similar clinical stage and biopsy Gleason score, although screen‐detected cases had significantly lower prostate‐specific antigen (PSA) levels at diagnosis.
• ? Men from the screening arm had a significantly higher PFS (P= 0.003), MFS (P < 0.001) and CSS (P= 0.048).
• ? In multivariable models adjusting for age, PSA level, clinical stage, and biopsy Gleason score, the screening group had a significantly lower risk of biochemical recurrence (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23–0.83, P= 0.011) and metastasis (HR 0.18, 95% CI 0.06–0.59, P= 0.005).
• ? Additionally adjusting for tumour volume and other RP pathology features, there was no longer a significant difference in biochemical recurrence between the screening and control arms.
• ? Limitations of the present study include lead‐time bias and non‐randomised treatment selection.

CONCLUSIONS

• ? After RP, screen‐detected cases had significantly improved PFS, MFS and CSS compared with controls within the available follow‐up time.
• ? The screening arm remained significantly associated with lower rates of biochemical recurrence and metastasis after adjusting for other preoperative variables.
• ? However, considering also RP pathology, the improved outcomes in the screening group appeared to be mediated by a significantly lower tumour volume.

     

Transatlantic Consensus Group on active surveillance and focal therapy for prostate cancer

Study Type – Prognosis (inception cohort) Level of Evidence 2a What's known on the subject? and What does the study add? There is little data on the utility of digital rectal examination (DRE) as a diagnostic tool in the era of prostate‐specific antigen (PSA) testing. Using a population‐based database, we found that detection of prostate cancer while still localized among men with high‐grade PSA‐occult disease may result in survival benefit.

OBJECTIVE

• ? To determine whether detection of high‐grade prostate cancer while still clinically localised on digital rectal examination (DRE) can improve survival in men with a normal prostate‐specific antigen (PSA) level.

PATIENTS AND METHODS

• ? From the Surveillance, Epidemiology and End Results database, 166 104 men with prostate cancer diagnosed between 2004 and 2007 were identified.
• ? Logistic regression was used to identify factors associated with the occurrence of palpable, PSA‐occult (PSA level of <2.5 ng/mL), Gleason score 8–10 prostate cancer.
• ? Fine and Gray's and Cox multivariable regressions were used to analyse whether demographic, treatment, and clinicopathological factors were associated with the risk of prostate cancer‐specific mortality (PCSM) and all‐cause mortality (ACM), respectively.

RESULTS

• ? Both increasing age (adjusted odds ratio [aOR] 1.02, 95% confidence interval (CI) 1.01–1.03; P < 0.001) and White race (aOR 1.26, 95% CI 1.03–1.54; P= 0.027) were associated with palpable, Gleason 8–10 prostate cancer. Of 166 104 men, 685 (0.4%) had this subset of prostate cancer.
• ? Significant factors associated with risk of PCSM included PSA level (adjusted hazard ratio [aHR] 0.71, 95% CI 0.51–0.99; P= 0.04), higher Gleason score (aHR 2.20, 95% CI 1.25–3.87; P= 0.006), and T3–T4 vs T2 disease (aHR 3.11, 95% CI 1.79–5.41; P < 0.001).
• ? Significant factors associated with risk of ACM included age (aHR 1.03, 95% CI 1.01–1.06; P= 0.006), higher Gleason score (aHR 2.05, 95% CI 1.36–3.09; P < 0.001), and T3–T4 vs T2 disease (aHR 2.11, 95% CI 1.38–3.25, P < 0.001)

CONCLUSIONS

• ? Clinically localised disease on DRE among men with PSA‐occult high‐grade prostate cancer was associated with improved PCSM and ACM, suggesting that DRE in this cohort (older age and White race) may have the potential to improve survival.

     

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.

     

Transrectal ultrasonography-guided biopsy does not reliably identify dominant cancer location in men with low-risk prostate cancer

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The widespread use of serum PSA testing followed by TRUS‐guided biopsy have resulted in profound prostate cancer stage migration with many patients presenting with focal rather than multifocal disease. There is increasing interest in the use of focal rather than whole‐gland treatment. However, current biopsy schemes may still miss cancer or, even when cancer is identified, its extent or grade might not be accurately characterized. In order for focal therapy to be effective, the area of highest tumour volume and/or grade needs to localized accurately. The aim of this study was to assess how well biopsy, as currently performed, locates the focus of highest prostate cancer volume and/or grade.

OBJECTIVE

• ? To evaluate the ability of transrectal ultrasonography (TRUS)‐guided extended core biopsy to identify the dominant tumour accurately in men with early stage prostate cancer.

PATIENTS AND METHODS

• ? Patients with early stage, low‐risk prostate cancer who subsequently underwent radical prostatectomy (RP) and had complete surgical specimens were identified.
• ? Re‐review was performed by a single uropathologist using ImageJ software to identify tumour location, dominant grade (DG) and dominant volume (DV).
• ? Pathology findings were then compared with biopsy results.

RESULTS

• ? A total of 51 men with early stage, low‐risk prostate cancer, who had undergone RP, had complete specimens for review and a median of 15 biopsy cores taken for diagnosis and grading.
• ? Sixteen men had a single diagnostic biopsy, 21 had one repeat biopsy, and 14 had two or more repeat biopsies.
• ? Compared with surgical findings, biopsy correctly identified the sextant with the largest tumour volume in 55% (95% CI 0.5–0.6) of specimens and the highest grade in 37% (95 CI 0.3–0.5).
• ? No demographic or clinical factors were significantly associated with identification of DG. Interval between last biopsy and RP, total tissue length taken and total length of tumour identified were significantly associated with correct identification of DV.

CONCLUSIONS

• ? Our findings show that TRUS‐guided biopsy detects and localizes DV better than it does DG.
• ? Even with an extended scheme, TRUS‐guided biopsy does not reliably identify dominant cancer location in this low‐risk cohort of men with early stage prostate cancer.
• ? TRUS‐guided biopsy may perform better in similar men with low stage, but higher volume disease.

     

Underestimation of Gleason score at prostate biopsy reflects sampling error in lower volume tumours

Study Type – Diagnostic (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The Gleason score of prostate cancer is frequently underestimated at the time of diagnostic biopsy, although the contribution of sampling error to its incidence is unknown. We show that under‐graded tumours are significantly smaller that tumours concordant for the higher grade, indicating that incomplete tumour sampling plays a significant role in Gleason score assignment error.

OBJECTIVE

• ? To determine the influence of tumour and prostate gland volumes on the underestimation of prostate cancer Gleason score in diagnostic core biopsies.

PATIENTS AND METHODS

• ? Patients undergoing radical prostatectomy with matched diagnostic biopsies were identified from a prospectively recorded database.
• ? Tumour volumes were measured in serial whole‐mount sections with image analysis software as part of routine histological assessment.
• ? Differences in various metrics of tumour and prostate volume between upgraded tumours and tumours concordant for the lower or higher grade were analysed.

RESULTS

• ? In all, 684 consecutive patients with Gleason score 6 or 7 prostate cancer on diagnostic biopsy were identified.
• ? Of 298 patients diagnosed with Gleason 6 tumour on biopsy, 201 (67.4%) were upgraded to Gleason 7 or higher on final pathology. Similarly, of 262 patients diagnosed with Gleason 3 + 4 = 7 prostate cancer on initial biopsy, 60 (22.9%) were upgraded to Gleason score 4 + 3 = 7 or higher.
• ? Tumours upgraded from Gleason 6 to 7 had a significantly lower index tumour volume (1.73 vs 2 mL, P= 0.029), higher calculated prostate volume (41.6 vs 39 mL, P= 0.017) and lower relative percentage of tumour to benign glandular tissue (4.3% vs 5.9%, P= 0.001) than tumours concordant for the higher grade.
• ? Similarly, tumours that were Gleason score 3 + 4 on biopsy and upgraded on final pathology to 4 + 3 were significantly smaller as measured by both total tumour volume (2.3 vs 3.3 mL, P= 0.005) and index tumour volume (2.2 vs 3, P= 0.027) and occupied a smaller percentage of the gland volume (6.3% vs 8.9%, P= 0.017) compared with tumours concordant for the higher grade.
• ? On multivariate analysis, lower prostate weight (hazard ratio 0.97, 95% confidence interval 0.96–0.99, P < 0.001) and larger total tumour volume (hazard ratio 1.87, 95% confidence interval 1.4–2.6, P < 0.001) independently predicted an upgrade in Gleason score from 6 to 7. In tumours upgraded from biopsy Gleason 3 + 4, only higher index tumour volume (hazard ratio 3.1, 95% confidence interval 1.01–9.3, P= 0.048) was a significant predictor of upgrading on multivariate analysis.

CONCLUSIONS

• ? Under‐graded tumours are significantly smaller than tumours concordant for the higher grade, indicating that incomplete tumour sampling plays a significant role in Gleason score assignment error.
• ? Surrogate measures of tumour volume may predict those at greatest risk of Gleason score upgrade.

     

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.

     

The role of transrectal saturation biopsy in tumour localization: pathological correlation after retropubic radical prostatectomy and implication for focal ablative therapy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? The traditional transrectal sextant and extended biopsy schemes demonstrated low accuracy in predicting unilateral prostate cancer on radical prostatectomy specimens. We examined the accuracy of an initial saturation biopsy (24‐core) to predict unilateral prostate cancer on radical prostatectomy specimens.

OBJECTIVE

• ? To evaluate the accuracy of an initial 24‐core prostate biopsy scheme (PBx24) in predicting unilateral prostate cancer (PCa) in radical prostatectomy (RP) specimens.

PATIENTS AND METHODS

• ? Between 2005 and 2008, 203 consecutive patients underwent PBx24 followed by RP for PCa. The area under the curve (AUC) was used to evaluate the accuracy of unilateral PCa on PBx24 to predict unilateral PCa in RP specimens.
• ? The positive predictive value (PPV) and negative predictive value (NPV) were also calculated. Moreover, in patients with unilateral PCa on biopsy, univariable and multivariable logistic regression analyses tested the relationship between the presence of unilateral PCa in an RP specimen and the variables: age, prostate‐specific antigen (PSA), total prostate volume, clinical stage, primary Gleason grade, secondary Gleason grade and the number of positive cores.

RESULTS

• ? PCa cores were unilateral in 115 patients (56.7%) on biopsy. Of those, only 26 (22.6%) had unilateral PCa in the RP specimen (AUC, 72.9%; PPV, 22.6%; NPV, 98.8%). In patients with clinically low‐risk tumours, only 17 of 63 (27%) had a unilateral PCa on PBx24 and in the RP specimen (AUC, 59.1%; PPV, 27.0%; NPV, 100.0%).
• ? None of the examined variables was an independent predictor of the presence of unilateral PCa in the RP specimen (all P > 0.05).

CONCLUSIONS

• ? Initial PBx24 is not sufficiently accurate to be dependable as a method of predicting tumour laterality in RP specimens. Therefore, the use of PBx24 to guide hemi‐ablation therapy of PCa may lead to mistreatment in a considerable proportion of patients.
• ? Moreover, none of the routinely available clinical and pathological characteristics appears to improve the ability of unilateral PCa on biopsy to predict unilateral PCa in the RP specimen.

     

Biopsy Gleason score and the duration of testosterone suppression among men treated with external beam radiation and 6 months of combined androgen blockade

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The return of testosterone to normal levels following short‐course androgen blockade in prostate cancer is variable. Factors associated with a longer time to recovery include older age and lower baseline testosterone level. In this study, we found that among men treated with 6 months of combined androgen blockade and radiation therapy, higher biopsy Gleason grade was associated with a shorter time to testosterone normalization.

OBJECTIVE

• ? To determine whether the biopsy Gleason score is associated with duration of testosterone suppression following 6 months of combined androgen blockade (CAB) and radiation therapy (RT) in men with prostate cancer (PCa).

PATIENTS AND METHODS

• ? The study cohort consisted of 221 men with PCa treated with RT and 6 months of CAB between 1996 and 2005.
• ? We defined the duration of testosterone suppression as the time between the last day of CAB and the date the testosterone returned to ≥252 ng/dL. We used Cox regression multivariable analysis to relate biopsy Gleason score to duration of testosterone suppression following cessation of CAB.

RESULTS

• ? A biopsy Gleason score of 8–10 had an adjusted hazard ratio (AHR) of 1.56 (95% confidence interval [CI] 1.04, 2.34; P= 0.03) for a shorter time to testosterone normalization relative to Gleason 6. Specifically, the 51 men with biopsy Gleason score of 8–10 had a median time to testosterone normalization of 17.0 months compared with 22.1 months and 23.8 months for those with biopsy Gleason ≤6 and 7, respectively.
• ? Increasing age was significantly associated with a longer duration of testosterone suppression (AHR of 0.95 [95% CI 0.92, 0.97; P < 0.001]) as was a higher baseline PSA (AHR 0.82 [95% CI 0.69, 0.97; P= 0.02]).

CONCLUSION

• ? A biopsy Gleason score of 8–10 was associated with a shorter period of testosterone suppression following 6 months of CAB and RT. These data are consistent with the hypothesis that a factor released from high‐grade PCa cells may impact on testosterone production.

     

Effect of delaying surgery on radical prostatectomy outcomes: a contemporary analysis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? For patients electing surgical treatment, the question of the effect of surgical delay on clinical outcomes in prostate cancer is controversial. In this study we examined the effect of delay from diagnosis to surgery on outcomes in men with localized prostate cancer and found no association between time to surgery and risk of biochemical recurrence, even for patients with longer delays and high‐risk disease. Men with localized prostate cancer can be reassured that reasonable delays in treatment will not influence disease outcomes.

OBJECTIVE

• ? To examine the effect of time from last positive biopsy to surgery on clinical outcomes in men with localized prostate cancer undergoing radical prostatectomy (RP).

PATIENTS AND METHODS

• ? We conducted a retrospective review of 2739 men who underwent RP between 1990 and 2009 at our institution.
• ? Clinical and pathological features were compared between men undergoing RP ≤ 60, 61–90 and >90 days from the time of prostate biopsy.
• ? A Cox proportional hazards model was used to analyse the association between clinical features and surgical delay with biochemical progression. Biochemical recurrence (BCR)‐free rates were assessed using the Kaplan–Meier method.

RESULTS

• ? Of the 1568 men meeting the inclusion criteria, 1098 (70%), 303 (19.3%) and 167 (10.7%) had a delay of ≤60, 61–90 and >90 days, respectively, between biopsy and RP. A delay of >60 days was not associated with adverse pathological findings at surgery.
• ? The 5‐year survival rate was similar among the three groups (78–85%, P= 0.11).
• ? In a multivariate Cox model, men with higher PSA levels, clinical stages, Gleason sums, and those of African‐American race were all at higher risk for developing BCR.
• ? A delay to surgery of >60 days was not associated with worse biochemical outcomes in a univariate and multivariate model.

CONCLUSIONS

• ? A delay of >60 days is not associated with adverse pathological outcomes in men with localized prostate cancer, nor does it correlate with worse BCR‐free survival.
• ? Patients can be assured that delaying treatment while considering therapeutic options will not adversely affect their outcomes.

     

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.

     

The relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Prior studies have shown that the PCA3 Score is indicative of prostate cancer significance and may aid in selecting men with clinically insignificant prostate cancer who could be candidates for active surveillance. This analysis of data from two studies enrolling 1,009 men shows that the PCA3 Score is associated with many biopsy and pathological features of the insignificant prostate cancer. The paper also provides guidance for the use of the PAC3 Assay in clinical practice.

OBJECTIVE

• ? To evaluate the relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance.

PATIENTS AND METHODS

• ? Clinical data from two multi‐centre European open‐label, prospective studies evaluating the clinical utility of the PCA3 assay in guiding initial and repeat biopsy decisions were analysed.
• ? First‐catch urine was collected after digital rectal examination (three strokes per lobe) and the PCA3 score was determined using the PROGENSA® PCA3 assay.
• ? Transrectal ultrasound‐guided biopsy (≥8 cores) and radical prostatectomy (RP) specimens were analysed by the local pathologist. The relationship between biopsy and RP outcomes with the PCA3 score was assessed.

RESULTS

• ? Of the 1009 men enrolled, 348 (34%) had a positive biopsy. The median and mean PCA3 scores were statistically significantly lower in men with biopsy Gleason score <7 vs ≥7, with clinical stage T1c vs T2a–T2c, T3a cancers, with ≤33% vs >33% positive biopsy cores and with ‘biopsy indolent’ vs ‘biopsy significant’ prostate cancer (indolent prostate cancer defined by biopsy Epstein criteria).
• ? In all, 175 men with a positive biopsy had a RP: median and mean PCA3 scores were statistically significantly lower in men with pathological Gleason score <7 vs ≥7, and with pathological stage T2a–T2c vs T3a–T3b cancers.

CONCLUSIONS

• ? The PCA3 score may combined with traditional tools aid in identifying men with clinically insignificant prostate cancer, as shown by biopsy and RP pathological features including biopsy Epstein criteria, who could be candidates for active surveillance.
• ? Treatment selection should be based on a combination of clinical and pathological variables. If one wants to use a threshold point to guide treatment decisions in clinical practice, a PCA3 score threshold of 20 may have the highest utility for selecting men with clinically insignificant prostate cancer in whom active surveillance may be appropriate; a PCA3 score threshold of 50 may be used to identify men at high risk of harbouring significant prostate cancer who are candidates for RP.
• ? Although the association between the PCA3 score and prostate cancer aggressiveness needs further evaluation, the inclusion of the PCA3 score into patient management strategies may provide clinicians with another tool to more accurately determine the course of treatment.

     

Genome gender diversity in affected sib-pairs with familial vesico-ureteric reflux identified by single nucleotide polymorphism linkage analysis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Despite a lack of randomised controlled trials, most men with locally advanced prostate cancer are recommended to undergo external beam radiotherapy (EBRT), often combined with long‐term androgen‐deprivation therapy (ADT). Many of these men are not offered radical prostatectomy (RP) by their treating urologist. Additionally, it is know that EBRT with long‐term ADT does provide good cancer control (88% at 10 years). We have previously published intermediate‐term follow‐up of a large series of men treatment with RP for cT3 prostate cancer. We report long‐term follow‐up of a large series of men treated with RP as primary treatment for cT3 prostate cancer. Our study shows that with long‐term follow‐up RP provides excellent oncological outcomes even at 20 years. While most men do require a multimodal treatment approach, many men can be managed successfully with RP alone.

OBJECTIVE

• ? To present long‐term survival outcomes after radical prostatectomy (RP) for patients with cT3 prostate cancer, as the optimal treatment for patients with clinical T3 prostate cancer is debated.

PATIENTS AND METHODS

• ? We identified 843 men who underwent RP for cT3 tumours between 1987 and 1997.
• ? Survival was estimated using the Kaplan–Meier method.
• ? Cox proportional hazards regression models were used to evaluate the association of clinicopathological features with outcome

RESULTS

• ? The median (range) postoperative follow‐up was 14.3 (0.1–23.5) years.
• ? Down‐staging to pT2 disease occurred in 26% (223/843) at surgery.
• ? Local recurrence‐free, systemic progression‐free and cancer‐specific survival for men with cT3 prostate cancer after RP was 76%, 72%, and 81%, respectively, at 20 years.
• ? On multivariate analysis, increasing RP Gleason score (hazard ratio [HR] 1.8; P= 0.01), non‐diploid chromatin content (HR 1.8; P= 0.01), positive surgical margins (HR 2.1; P= 0.007), and seminal vesicle invasion (HR 2.1; P= 0.005) were associated with a significant risk of prostate cancer death, while a more recent year of surgery was associated with a decreased risk of cancer‐specific mortality (HR 0.88; P= 0.01)

CONCLUSIONS

• ? RP affords accurate pathological staging and may be associated with durable cancer control for cT3 prostate cancer, with 20 years of follow‐up presented here.
• ? RP as part of a multimodal treatment strategy therefore remains a viable treatment option for patients with cT3 tumours.

     

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.

     

Association of prostate cancer risk alleles with unfavourable pathological characteristics in potential candidates for active surveillance

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Men fail active surveillance for a variety of reasons; however, no single reliable biomarker has been found to date which will identify these men from the outset. We know that there are about 35 prostate cancer risk alleles which have been discovered to influence risk of prostate cancer, from large‐scale genome‐wide association studies. Some of these have been associated with aggressive prostate cancer. Nobody has examined the potential for these risk alleles to predict men who might fail active surveillance. This study adds to the growing evidence that single nucleotide polymorphisms may be able to identify men who have aggressive prostate cancers, and that this could be part of a risk algorithm used in active surveillance protocols.

OBJECTIVE

• ? To assess whether the carrier status of 35 risk alleles for prostate cancer (CaP) is associated with having unfavourable pathological features in the radical prostatectomy specimen in men with clinically low risk CaP who fulfil commonly accepted criteria as candidates for active surveillance.

PATIENTS AND METHODS

• ? We studied men of European ancestry with CaP who fulfilled the commonly accepted clinical criteria for active surveillance (T1c, prostate‐specific antigen <10 ng/mL, biopsy Gleason ≤6, three or fewer positive cores, ≤50% tumour involvement/core) but instead underwent early radical prostatectomy.
• ? We genotyped these men for 35 CaP risk alleles. We defined ‘unfavourable’ pathological characteristics to be Gleason ≥7 and/or ≥ pT2b in their radical prostatectomy specimen.

RESULTS

• ? In all, 263 men (median age 60 [46–72] years) fulfilled our selection criteria for active surveillance, and 58 of 263 (22.1%) were found to have ‘unfavourable’ pathological characteristics.
• ? The frequencies of three CaP risk alleles (rs1447295 [8q24], P= 0.004; rs1571801 [9q33.2], P= 0.03; rs11228565 [11q13], P= 0.02) were significantly higher in men with ‘unfavourable’ pathological characteristics.
• ? Two other risk alleles were proportionately more frequent (rs10934853 [3q21], P= 0.06; rs1859962 [17q24], P= 0.07) but did not achieve nominal statistical significance.
• ? Carriers of any one of the significantly over‐represented risk alleles had twice the likelihood of unfavourable tumour features (P= 0.03), and carriers of any two had a sevenfold increased likelihood (P= 0.001).
• ? Receiver–operator curve analysis demonstrated an area under the curve of 0.66, suggesting that the number of single nucleotide polymorphisms carried provided discrimination between men with ‘favourable’ and ‘unfavourable’ tumour features in their prostatectomy specimen.

CONCLUSION

• ? In potential candidates for active surveillance, certain CaP risk alleles are more prevalent in patients with ‘unfavourable’ pathological characteristics in their radical prostatectomy specimen.

     

Characteristics and clinical significance of prostate cancers missed by initial transrectal 12-core biopsy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 3a What's known on the subject? and What does the study add? Initial transrectal 12‐core biopsy has a small but definite risk of missing anterior significant prostate cancers irrespective of age, PSA, prostate volume and DRE findings. Our study yields valuable information for diagnosis and treatment decision of prostate cancer based on transrectal 12‐core biopsy.

OBJECTIVE

• ? To characterize prostate cancers missed by initial transrectal 12‐core biopsy.

PATIENTS AND METHODS

• ? Between 2002 and 2008, 715 men with prostate‐specific antigen levels in the range 2.5–20 ng/mL or abnormal digital rectal examination underwent three‐dimensional 26‐core prostate biopsy (i.e. a combination of transrectal 12‐core biopsy and transperineal 14‐core biopsy) on initial examination.
• ? Of the 257 patients diagnosed with cancer, 120 patients subsequently underwent radical prostatectomy.
• ? Cancers were grouped into TR12‐negative cancers (i.e. not detected through transrectal 12‐core biopsy but detected through transperineal 14‐core biopsy) and TR12‐positive (i.e. detected through transrectal 12‐core biopsy) cancers.
• ? Clinicopathological characteristics of the TR12‐negative and TR12‐positive cancers were evaluated.

RESULTS

• ? TR12‐negative cancers comprised 21% of the three‐dimensional 26‐core biopsy‐detected cancers.
• ? The frequency of cancers with a biopsy Gleason score ≤6 and that of cancers with a biopsy primary Gleason grade ≤3 was higher in TR12‐negative cancers, at 58% and 83%, respectively, than in TR12‐positive cancers, at 25% (P < 0.001) and 53% (P < 0.001), respectively.
• ? The median number of positive cores in TR12‐negative cancers was two out of 26.
• ? TR12‐negative cancers were more frequently located anteriorly than posteriorly.
• ? The incidence of the TR12‐negative cancers was not associated significantly with any clinical variable.

CONCLUSION

• ? Many of the cancers missed by initial transrectal 12‐core biopsy are probably low‐grade and low‐volume diseases, although initial transrectal 12‐core biopsy has a small but definite risk of missing anterior significant cancers.

     

Measurement of peri-prostatic fat thickness using transrectal ultrasonography (TRUS): a new risk factor for prostate cancer

Study Type – Prognosis (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? ADIPOSE tissue secretes various endocrine and paracrine mediators. Some authors have begun to consider whether peri‐prostatic fat (PPF) may interact with the prostate and play a role in carcinogenesis. It has recently been shown that the PPF quantity measured by CT is associated with more aggressive disease in patients undergoing radiation therapy. Our group studied a population not yet diagnosed with prostate cancer. By doing so we were able to identify PPF thickness on transrectal ultrasonography as a risk factor for prostate cancer detection upon biopsy, and as a risk factor for high‐grade disease. Our study also raises interesting questions about the underlying mechanisms of the association between PPF quantity and prostate cancer.

OBJECTIVE

• ? To determine if the amount of peri‐prostatic fat (PPF) on transrectal ultrasonography (TRUS) is a risk factor for incident prostate cancer overall and high‐grade prostate cancer (Gleason ≥4).

PATIENTS AND METHODS

• ? A prospectively maintained database of patients undergoing prostate biopsy at Princess Margaret Hospital for cancer suspicion was used.
• ? All TRUS examinations were retrospectively reviewed upon ‘blinding’ to outcome.
• ? PPF thickness, measured as the distance between the prostate and the pubic bone, was used as an index of the quantity of PPF.
• ? PPF measurements, together with other prostate cancer risk factors, were evaluated against prostate cancer and high‐grade prostate cancer detection upon biopsy with univariable and multivariable logistic regression and area under the receiver operating characteristic curve (AUC) analysis.

RESULTS

• ? Of the 931 patients, 434 (47%) were diagnosed with prostate cancer and 218 (23%) were diagnosed with high‐grade prostate cancer.
• ? The mean (range) PPF thickness was 5.3 (0–15) mm.
• ? Increasing PPF thickness was associated with prostate cancer and high‐grade prostate cancer diagnosis, with graded effect. When adjusting for other variables, the odds of detecting any prostate cancer and high‐grade prostate cancer increased 12% (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.02–1.23) and 20% (OR 1.20, 95% CI 1.07–1.34), respectively, for each millimetre increase in PPF thickness.
• ? The AUCs for the association of PPF with prostate cancer and high‐grade prostate cancer were 0.58 (95% CI 0.54–0.62) and 0.59 (95% CI 0.55–0.64), respectively.

CONCLUSION

• ? The amount of PPF can be estimated with TRUS and is a predictor of prostate cancer and high‐grade prostate cancer at biopsy. To our knowledge, this study is the first to investigate PPF quantity in patients without prior prostate cancer diagnosis.