Selection Criteria For Active Surveillance Research Articles

Expanding inclusion criteria for active surveillance in intermediate-risk prostate cancer: a machine learning approach.

To develop new selection criteria for active surveillance (AS) in intermediate-risk (IR) prostate cancer (PCa) patients. Retrospective study including patients from 14 referral centers who underwent pre-biopsy mpMRI, image-guided biopsies and radical prostatectomy. The cohort included biopsy-naive IR PCa patients who met the following inclusion criteria: Gleason Grade Group (GGG) 1-2, PSA < 20ng/mL, and cT1-cT2 tumors. We relied on a recursive machine learning partitioning algorithm developed to predict adverse pathological features (i.e., ≥ pT3a and/or pN + and/or GGG ≥ 3). A total of 594 patients with IR PCa were included, of whom 220 (37%) had adverse features. PI-RADS score (weight:0.726), PSA density (weight:0.158), and clinical T stage (weight:0.116) were selected as the most informative risk factors to classify patients according to their risk of adverse features, leading to the creation of five risk clusters. The adverse feature rates for cluster #1 (PI-RADS ≤ 3 and PSA density < 0.15), cluster #2 (PI-RADS 4 and PSA density < 0.15), cluster #3 (PI-RADS 1-4 and PSA density ≥ 0.15), cluster #4 (normal DRE and PI-RADS 5), and cluster #5 (abnormal DRE and PI-RADS 5) were 11.8, 27.9, 37.3, 42.7, and 65.1%, respectively. Compared with the current inclusion criteria, extending the AS criteria to clusters #1 + #2 or #1 + #2 + #3 would increase the number of eligible patients (+ 60 and + 253%, respectively) without increasing the risk of adverse pathological features. The newly developed model has the potential to expand the number of patients eligible for AS without compromising oncologic outcomes. Prospective validation is warranted.

MP43-16 RACIAL DISPARITIES IN RATES OF GLEASON GRADE RECLASSIFICATION IN A MULTI-INSTITUTIONAL PROSTATE CANCER ACTIVE SURVEILLANCE COHORT: A PENNSYLVANIA UROLOGY REGIONAL COLLABORATIVE (PURC) ANALYSIS

You have accessJournal of UrologyCME1 May 2022MP43-16 RACIAL DISPARITIES IN RATES OF GLEASON GRADE RECLASSIFICATION IN A MULTI-INSTITUTIONAL PROSTATE CANCER ACTIVE SURVEILLANCE COHORT: A PENNSYLVANIA UROLOGY REGIONAL COLLABORATIVE (PURC) ANALYSIS Rohit Reddy, David Strauss, Matthew Loecher, Kaynaat Syed, John Danella, Serge Ginzburg, Laurence Belkoff, Jeffrey Tomaszewski, Edouard Trabulsi, Eric A. Singer, Bruce L. Jacobs, Jay Raman, Thomas Guzzo, Thomas Guzzo, Robert Uzzo, and Adam C. Reese Rohit ReddyRohit Reddy More articles by this author , David StraussDavid Strauss More articles by this author , Matthew LoecherMatthew Loecher More articles by this author , Kaynaat SyedKaynaat Syed More articles by this author , John DanellaJohn Danella More articles by this author , Serge GinzburgSerge Ginzburg More articles by this author , Laurence BelkoffLaurence Belkoff More articles by this author , Jeffrey TomaszewskiJeffrey Tomaszewski More articles by this author , Edouard TrabulsiEdouard Trabulsi More articles by this author , Eric A. SingerEric A. Singer More articles by this author , Bruce L. JacobsBruce L. Jacobs More articles by this author , Jay RamanJay Raman More articles by this author , Thomas GuzzoThomas Guzzo More articles by this author , Thomas GuzzoThomas Guzzo More articles by this author , Robert UzzoRobert Uzzo More articles by this author , and Adam C. ReeseAdam C. Reese More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002609.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Active surveillance (AS) is an established management option for patients with low-risk prostate cancer (CaP), with favorable long-term oncologic outcomes. Previous literature has shown significant racial CaP disparities with African-American (AA) men having a higher incidence of disease and more aggressive tumors. The purpose of this study is to analyze a prospectively maintained multi-institutional AS database to compare Gleason grade reclassification rates on confirmatory biopsy stratified by race. METHODS: The Pennsylvania Urological Regional Collaborative (PURC) is a prospectively maintained CaP quality improvement collaborative. The PURC database was queried for low risk CaP men on AS divided by race (AA vs Caucasian/Other). The primary outcome of interest was the rate of Gleason grade reclassification at the time of confirmatory biopsy. RESULTS: The study cohort included 536 patients with low risk CaP on AS, comprised of 119 (22.2%) AA and 417 (77.8%) Caucasian/Other men. Other than BMI, there were no significant differences in either patient demographics or index biopsy parameters between groups (Table 1). AA men had a significantly higher rate of grade reclassification (35.3% vs 25.4%, p=0.034). On multivariate analysis, AA race was an independent predictor of grade reclassification (OR 1.82, p=0.042) (Table 2). CONCLUSIONS: Established AS selection criteria and surveillance protocols fail to account for potential racial disparities in oncologic outcomes among patients with CaP. AA men in PURC exhibited a higher rate of grade reclassification on confirmatory biopsy, suggesting that AA men may need alternate AS surveillance criteria potentially including adjunct studies (mpMRI, genomic studies) to accurately risk stratify their CaP. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e747 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rohit Reddy More articles by this author David Strauss More articles by this author Matthew Loecher More articles by this author Kaynaat Syed More articles by this author John Danella More articles by this author Serge Ginzburg More articles by this author Laurence Belkoff More articles by this author Jeffrey Tomaszewski More articles by this author Edouard Trabulsi More articles by this author Eric A. Singer More articles by this author Bruce L. Jacobs More articles by this author Jay Raman More articles by this author Thomas Guzzo More articles by this author Thomas Guzzo More articles by this author Robert Uzzo More articles by this author Adam C. Reese More articles by this author Expand All Advertisement PDF DownloadLoading ...

MP43-10 IMPACT OF FAMILY HISTORY AND GERMLINE GENETIC RISK VARIANTS ON LONG-TERM OUTCOMES OF ACTIVE SURVEILLANCE-ELIGIBLE PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022MP43-10 IMPACT OF FAMILY HISTORY AND GERMLINE GENETIC RISK VARIANTS ON LONG-TERM OUTCOMES OF ACTIVE SURVEILLANCE-ELIGIBLE PROSTATE CANCER Florian Rumpf, Anna Plym, Jane Vaselkiv, Mark Preston, Adam Kibel, Lorelei Mucci, and Keyan Salari Florian RumpfFlorian Rumpf More articles by this author , Anna PlymAnna Plym More articles by this author , Jane VaselkivJane Vaselkiv More articles by this author , Mark PrestonMark Preston More articles by this author , Adam KibelAdam Kibel More articles by this author , Lorelei MucciLorelei Mucci More articles by this author , and Keyan SalariKeyan Salari More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002609.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A family history of prostate cancer (PCa) and BRCA/DNA repair gene-associated cancers are risk factors for developing prostate cancer. In the last decade, >260 PCa-associated single nucleotide polymorphisms (SNPs) have been identified through large-scale genome-wide association studies that strongly stratify lifetime risk of prostate cancer. Few studies have examined the prognostic value of family history or PCa germline risk variants in patients with favorable-risk PCa eligible for active surveillance (AS). Here, we evaluate the impact of a positive family history and germline risk SNPs on outcomes on AS-eligible patients. METHODS: In a prospective cohort of 39,427 U.S. men in the Health Professionals Follow-up Study, 1,367 were diagnosed with clinically favorable-risk (NCCN very low-, low-, or favorable intermediate-risk) PCa from 1986 to 2016 and underwent genome-wide SNP genotyping. During the 30-year follow-up, 263 patients experienced disease recurrence and 52 patients died of PCa. A polygenic risk score was derived from 269 SNPs associated with development of PCa. Two loci associated with PCa survival were also assessed. Multivariable Cox proportional hazards models were used to estimate the association between family history of prostate, breast, or pancreatic cancer, germline risk SNPs, and PCa recurrence or death through 2019. RESULTS: The median follow up time from diagnosis was 14.1 years. A family history of prostate, breast, or pancreatic cancer was observed in 494 (36%) patients. Men with a positive family history had an 83% greater risk of PCa-specific death (95% CI 1.06-3.17, p=0.03), and greater than that of men with a family history of PCa alone. The polygenic risk score was not associated with either PCa recurrence or death. However, focusing on 2 loci on 8q24 and 19q13 with the strongest evidence in the literature for association with PCa aggressiveness, we observed a significant association between rs2735839 on 19q13 and PCa-specific death (HR 1.81, 95% CI 1.04-3.17, p=0.037). Using a risk score giving one point each to a positive family history and rs2735839 risk allele, each point of the heritable risk score was associated with a 72% increased risk of PCa-specific death (95% CI 1.16-2.54, p=0.006). CONCLUSIONS: Our study found that patients with AS-eligible PCa with a family history of prostate, breast, or pancreatic cancer or a 19q13 germline risk allele had elevated risks of PCa-specific death. These findings have implications for how germline genetic risk should be factored into AS selection criteria. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e744 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Florian Rumpf More articles by this author Anna Plym More articles by this author Jane Vaselkiv More articles by this author Mark Preston More articles by this author Adam Kibel More articles by this author Lorelei Mucci More articles by this author Keyan Salari More articles by this author Expand All Advertisement PDF DownloadLoading ...

Active surveillance for prostate cancer: selection criteria, guidelines, and outcomes.

Active surveillance (AS) has been widely adopted for the management of men with low-risk prostate cancer. However, there is still a lack of consensus surrounding the optimal approach for monitoring men in AS protocols. While conservative management aims to reduce the burden of invasive testing without compromising oncological safety, inadequate assessment can result in misclassification and unintended over- or undertreatment, leading to increased patient morbidity, cost, and undue risk. No universally accepted AS protocol exists, although numerous strategies have been developed in an attempt to optimize the management of clinically localized disease. Variability in selection criteria, reclassification, triggers for definitive treatment, and follow-up exists between guidelines and institutions for AS. In this review, we summarize the landscape of AS by providing an overview of the existing AS protocols, guidelines, and their published outcomes. A comprehensive electronic search was performed to identify representative studies and guidelines pertaining to AS selection criteria and outcomes. While AS is a safe and increasingly utilized treatment modality for lower-risk forms of PCa, ongoing research is needed to optimize patient selection as well as surveillance protocols along with improved implementation across practices. Further, assessment of companion risk assessment tools, such as mpMRI and tissue-based biomarkers, is also needed and will require rigorous prospective study.

The impact of a positive family history on clinical and pathologic outcomes of active surveillance for prostate cancer.

225 Background: Active surveillance (AS) is the preferred management strategy for men with low-risk prostate cancer. However, approximately one in three men on AS experience progression of disease leading to treatment within 5 years, highlighting an urgent unmet need to reliably distinguish indolent from aggressive prostate cancer and improve patient selection criteria for AS. Germline genetic testing for DNA repair gene mutations is now recommended for patients with newly diagnosed prostate cancer and a strong family history of prostate cancer or BRCA1/2-related cancers, as such mutations have been associated with more aggressive forms of the disease. Here, we investigated the impact of family history on AS outcomes, under the hypothesis that men at high genetic risk for prostate cancer are at greater risk for progression to treatment on AS. Methods: We retrospectively reviewed detailed family history data of 958 patients from our institutional database of men enrolled in AS between 1997-2019. Data on family history of prostate cancer and hereditary cancer syndrome ( BRCA1/2-related prostate, breast, ovarian and/or pancreatic cancers) were collected and integrated into a composite family history score incorporating the number of relatives with each cancer weighted by degree of relatedness. A strong family history was defined as a composite score representing &gt; 1 first-degree relative equivalent. The primary outcome was biopsy progression and secondary outcomes were adverse pathologic features at prostatectomy and biochemical recurrence. Statistical analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: In univariate analysis, a strong family history suggestive of a hereditary cancer syndrome (HR 1.37 [1.03-1.90], P = 0.033) was associated with a significant increased risk of biopsy progression; however, any family history of prostate cancer (HR 1.10 [0.89-1.35], P = 0.38) and a strong family history of prostate cancer (HR 1.35 [0.92-1.98], P = 0.13) were not significant. In multivariate analysis, a strong family history suggestive of a hereditary cancer syndrome remained a statistically significant predictor of biopsy progression (HR 1.42 [1.03-1.96], P = 0.03), after adjusting for age, percent core involvement on initial biopsy and PSA density. No significant association was found between family history and adverse features on surgical pathology or biochemical recurrence. Conclusions: A positive family history suggestive of a hereditary cancer syndrome is associated with an increased risk of biopsy progression on AS and is an independent predictor of biopsy progression. Men with such a family history may still be safely offered AS but should be counseled about the higher risk of progression. Further work to investigate the underlying genetic factors responsible for this increased risk is warranted.

The clinical impact of strict criteria for active surveillance of prostate cancer in Korean population: Results from a prospective cohort.

PurposeTo evaluate the clinical impact of strict selection criteria for active surveillance (AS) of prostate cancer in a Korean population.Materials and MethodsA single-center, prospectively collected AS cohort from December 2016 to February 2019 was used. Following pre-determined criteria, patients were categorized into “strict AS” and “non-strict AS” groups. Clinicopathological progression-free survival (PFS) and treatment-free survival (TFS) of the two groups were compared using the Kaplan–Meier curve and log-rank test. Age-adjusted hazard ratios for clinicopathological progression was calculated using Cox proportional regression analysis.ResultsOf 54 eligible patients, 25 and 29 were assigned to “strict AS” and “non-strict AS,” respectively. Clinicopathological progression and definitive treatment rates were 24.0% (6 of 25 patients) vs. 51.7% (15 of 29 patients) and 32.0% (8 of 25 patients) vs. 62.1% (18 of 29 patients) in “strict AS” and “non-strict AS” groups. Progress to high-risk cancer (pathologic T3 or surgical Gleason Grade 2 over) in radical prostatectomy was higher in “non-strict AS” than “strict AS”. PFS (mean 34.6±2.9 mo vs. 22.6±2.7 mo; p=0.025) and TFS (mean 31.8±3.2 mo vs. 19.6±2.4 mo; p=0.018) favor the “strict AS” group than “non-strict AS” group. Age-adjusted hazard ratio for clinicopathological progression of strict criteria was 0.36 (95% confidence interval, 0.14–0.94; p=0.04).ConclusionsPFS and TFS were better in the “strict AS” group than in the “non-strict AS” group. This finding should be informed to relevant patients during decision making and considered in Korean guidelines.

Selecting Patients with Small Renal Masses for Active Surveillance.

The incidentally discovered, clinically-localized, small renal mass (clinical stage T1aN0M0, ≤4cm) is the most commonly diagnosed entity in Renal Cell Carcinoma (RCC) - now accounting for at least 40% of newly diagnosed renal tumors. Given the above argument, Active Surveillance (AS) has emerged as a viable management strategy for SRM. This review will examine and discuss the existing literature regarding selection criteria for AS. AS of clinical T1a renal masses is emerging as a safe and effective management strategy in selected patients, yet appropriate patient selection and counseling remains an area of great interest. Long-term clinical outcomes are just beginning to be reported, thus much of the supporting evidence on AS and patient selection is based on retrospective data of heterogeneous quality. Nevertheless, there are certain conclusions that can be drawn, despite these current limitations. Appropriate selection of candidates should include a comprehensive evaluation of competing health risks, tumor characteristics, and patient preferences.

This Month in Adult Urology

No AccessJournal of UrologyThis Month in Adult Urology1 Jun 2018This Month in Adult Urology Joseph A. SmithMD Joseph A. SmithJoseph A. Smith More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.076AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail References 1 : Incidence of extraprostatic extension at radical prostatectomy with pure Gleason score 3 + 3 = 6 (Grade Group 1) cancer: implications for whether Gleason score 6 prostate cancer should be renamed “not cancer” and for selection criteria for active surveillance. J Urol2018; 199: 1482. Link, Google Scholar 2 : Complications of recognized and unrecognized iatrogenic ureteral injury at time of hysterectomy: a population based analysis. J Urol2018; 199: 1540. Link, Google Scholar 3 : Worse urinary, sexual and bowel function cause emotional distress and vice versa in men treated for prostate cancer. J Urol2018; 199: 1464. Link, Google Scholar 4 : Detrusor acontractility after acute spinal cord injury—myth or reality?. J Urol2018; 199: 1565. Link, Google Scholar 5 : Development of a nationally representative coordinated registry network for prostate ablation technologies. J Urol2018; 199: 1488. Link, Google Scholar 6 : Effect of starting penile rehabilitation with sildenafil immediately after robot-assisted laparoscopic radical prostatectomy on erectile function recovery: a prospective randomized trial. J Urol2018; 199: 1600. Link, Google Scholar 7 : Comparing outcomes of robotic and open inguinal lymph node dissection in patients with carcinoma of the penis. J Urol2018; 199: 1518. Link, Google Scholar 8 : Purified protein derivative skin test prior to bacillus Calmette-Guérin therapy may have therapeutic impact in patients with nonmuscle invasive bladder cancer. J Urol2018; 199: 1446. Link, Google Scholar 9 : Impact of comorbidities on functional recovery from partial nephrectomy. J Urol2018; 199: 1433. Link, Google Scholar 10 : A randomized comparative study evaluating various cough stress tests and 24-hour pad test with urodynamics in the diagnosis of stress urinary incontinence. J Urol2018; 199: 1557. Link, Google Scholar 11 : Neoadjuvant dose dense MVAC versus gemcitabine and cisplatin in patients with cT3-4aN0M0 bladder cancer treated with radical cystectomy. J Urol2018; 199: 1452. Link, Google Scholar © 2018 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 199Issue 6June 2018Page: 1367-1369 Advertisement Copyright & Permissions© 2018 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joseph A. Smith More articles by this author Expand All Advertisement PDF downloadLoading ...

Incidence of Extraprostatic Extension at Radical Prostatectomy with Pure Gleason Score 3 + 3 = 6 (Grade Group 1) Cancer: Implications for Whether Gleason Score 6 Prostate Cancer Should be Renamed "Not Cancer" and for Selection Criteria for Active Surveillance

We assessed the risk of locally aggressive behavior in pure Gleason score 6 (Grade Group 1) prostate cancer using contemporary grading criteria. To our knowledge this has been studied in only 1 prior cohort. We evaluated consecutive radical prostatectomy specimens from an academic institution, including those from 3,291 men with Gleason score 6 and 4,202 with Gleason score 3 + 4 = 7 (Grade Group 2) disease between 2005 and 2016. For dichotomous variables the Pearson chi-square test was used. Of the 3,288 Gleason score 6 cancer cases 128 (3.9%) showed focal extraprostatic extension compared to 593 of the 4,202 (14.1%) with Gleason score 3 + 4 = 7 (p <0.0001). Of the 3,288 Gleason score 6 cancer cases 79 (2.4%) showed nonfocal extraprostatic extension compared to 639 of the 4,202 (15.2%) with Gleason score 3 + 4 = 7 (p <0.0001). The incidence of focal extraprostatic extension with Gleason score 3 + 4 = 7 with less than 5% Gleason pattern 4 was 129 of 1,147 cases (11.2%), which was between Gleason scores 6 and 3 + 4 = 7 with greater than 5% Gleason pattern 4. The incidence of nonfocal extraprostatic extension in Gleason score 3 + 4 = 7 with less than 5% Gleason pattern 4 was 96 of 1,147 cases (8.4%), which was between Gleason scores 6 and 3 + 4 = 7 with greater than 5% Gleason pattern 4. One of the 3,290 Gleason score 6 cases (0.03%) showed seminal vesicle invasion compared to 93 of the 4,202 (2.2%) of Gleason score 3 + 4 = 7 (p<0.0001). A limitation of our study was its retrospective design. It is not rare for pure Gleason score 6 prostate cancer to locally extend out of the prostate 3.9% focally and 2.4% nonfocally. In extremely rare cases Gleason score 6 can be associated with seminal vesicle invasion and yet not lymph node metastases. Our overall findings support the argument for continuing to use the term cancer for these tumors.

P039 - Favorable Gleason 3 + 4 prostate cancer shows comparable outcomes with Gleason 3 + 3 prostate cancer: Implications for the expansion of selection criteria for active surveillance

P039 - Favorable Gleason 3 + 4 prostate cancer shows comparable outcomes with Gleason 3 + 3 prostate cancer: Implications for the expansion of selection criteria for active surveillance

Selection Criteria for Active Surveillance of Patients with Prostate Cancer in Korea: A Multicenter Analysis of Pathology after Radical Prostatectomy.

PurposeKorean patients with prostate cancer (PC) typically present with a more aggressive disease than patients in Western populations. Consequently, it is unclear if the current criteria for active surveillance (AS) can safely be applied to Korean patients. Therefore, this study was conducted to define appropriate selection criteria for AS for patients with PC in Korea.Materials and MethodsWe conducted a multicenter retrospective study of 2,126 patients with low risk PC who actually underwent radical prostatectomy. The primary outcome was an unfavorable disease, which was defined by non-organ confined disease or an upgrading of the Gleason score to ≥ 7 (4+3). Predictive variables of an unfavorable outcome were identified by multivariate analysis using randomly selected training samples (n=1,623, 76.3%). We compared our selected criteria to various Western criteria for the primary outcome and validated our criteria using the remaining validation sample (n=503, 23.7%).ResultsA non-organ confined disease rate of 14.9% was identified, with an increase in Gleason score ≥ 7 (4+3) of 8.7% and a final unfavorable disease status of 20.8%. The following criteria were selected: Gleason score ≤ 6, clinical stage T1-T2a, prostate-specific antigen (PSA) ≤ 10 ng/mL, PSA density < 0.15 ng/mL/mL, number of positive cores ≤ 2, and maximum cancer involvement in any one core ≤ 20%. These criteria provided the lowest unfavorable disease rate (11.7%) when compared to Western criteria (13.3%-20.7%), and their validity was confirmed using the validation sample (5.9%).ConclusionWe developed AS criteria which are appropriate for Korean patients with PC. Prospective studies using these criteria are now warranted.

MP43-13 COMPARISON OF BIOCHEMICAL RECURRENCE FREE SURVIVAL AFTER RADICAL PROSTATECTOMY AMONG MEN IN ACTIVE SURVEILLANCE FOLLOWING GRADE RECLASSIFICATION AND MEN NEWLY DIAGNOSED WITH SIMILAR GRADE DISEASE

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance II1 Apr 2017MP43-13 COMPARISON OF BIOCHEMICAL RECURRENCE FREE SURVIVAL AFTER RADICAL PROSTATECTOMY AMONG MEN IN ACTIVE SURVEILLANCE FOLLOWING GRADE RECLASSIFICATION AND MEN NEWLY DIAGNOSED WITH SIMILAR GRADE DISEASE Clarissa Diniz, Ballentine Carter, Jonathan Epstein, and Mufaddal Mamawala Clarissa DinizClarissa Diniz More articles by this author , Ballentine CarterBallentine Carter More articles by this author , Jonathan EpsteinJonathan Epstein More articles by this author , and Mufaddal MamawalaMufaddal Mamawala More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1323AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Evaluate the biochemical recurrence free survival (bRFS) in men after radical prostatectomy (RP) triggered by Gleason score (GS) grade reclassification (GR) during active surveillance (AS) in order to inform patient decisions. METHODS We conducted a retrospective analysis of men undergoing RP from 1995-2015 and identified 2 groups; 122 men in AS who underwent RP following GR (7(3+4) or greater, grade group 2 and above) and 4433 men who underwent immediate RP (IRP) following a diagnosis of grade group 2 and above. bRFS was assessed using Kaplan Meir and multivariate Cox regression analyses. RESULTS Of 122 men in AS, 13 (10.7%) had biochemical recurrence (BCR) as compared to 777 of 4,433 (17.5%) men that underwent IRP (p =0.007). As compared to the IRP group, men on AS were significantly older (p <0.001), had a higher proportion of low volume cancers (p <0.001), a lower PSA density (p =0.001), and a lower rate of GS upgrade at surgery (p <0.001). bRFS was higher for men in the AS cohort compared to IRP group (p = 0.046, Fig 1). After adjustment for confounders, the difference in bRFS between groups was no longer significant (HR = 0.77; 95% CI, 0.41 to 1.46). CONCLUSIONS AS patients that are reclassified to grade group 2 and above have a higher bRFS after surgery as compared to those undergoing IRP with similar grade disease. These differences are likely due to selection criteria for AS. Our findings help inform patient decisions regarding the risk of entering an AS program. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e558-e559 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Clarissa Diniz More articles by this author Ballentine Carter More articles by this author Jonathan Epstein More articles by this author Mufaddal Mamawala More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Role of Multi-Parametric Magnetic Resonance Image and PIRADS Score in Patients with Prostate Cancer Eligible for Active Surveillance According PRIAS Criteria

Objective: To evaluate the prognostic role of multiparametric-MRI (mp-MRI) in patients with clinically localized prostate cancer (PCa) eligible for active surveillance (AS) according to Prostate Cancer Research International: Active Surveillance (PRIAS) criteria. Patients and Methods: We analyzed prospectively 73 patients with PCa and PRIAS criteria for low-risk disease. All patients fitted criteria for AS but optioned surgery treatment. The mp-MRI was performed to define the likelihood of malignancy according to the Prostate Imaging Reporting and Data System (PIRADS) score (1-5). Patients were divided in 2 groups: non-visible cancer lesion on MRI (PIRADS 2-3) and visible cancer (PIRADS 4-5). Preoperative clinical data (age, body mass index, prostate specific antigen (PSA) level, positive core biopsy, PSA density (PSAD)) and definitive pathological findings (staging, upgrading, unfavorable disease) were compared between groups. PIRADS score was correlated with pathological data to evaluate the prognostic role of mp-MRI; and preoperative variables and definitive pathology (upgrading, upstaging and unfavorable disease) were also assessed. Results: PSAD (p = 0.04) and pathological stage (p = 0.03) were significantly associated with the presence of visible disease. Visible disease was significantly associated with upstaging (p = 0.03). Correlation between PIRADS 5 and unfavorable disease was statistically significant (p = 0.02). The mp-MRI had adequate sensibility in detecting upstaging (92%), intermediate for upgrading (76%) and unfavorable disease (76%). Negative predictive value was higher for upstaging than for upgrading or unfavorable disease (96 vs. 68% and 64%). Multivariate logistic regression revealed that PIRADS 5 was a significant predictor of upstaging (p = 0.05, OR 16.12) and unfavorable disease (p = 0.01, OR 6.53). Conclusion: A visible lesion on mp-MRI strongly predicts significant PCa in patients eligible for AS according to PRIAS criteria, based on upstaging and unfavorable disease. We believe that mp-MRI is an important tool and should be added to clinical selection criteria for AS.

Validation of Selection Criteria for Active Surveillance in Prostate Cancer.

Considerable Proportion of Prostate Cancer (PCa) patients suitable for Active Surveillance (AS) harbour aggressive disease at surgical histopathology. Identification of truly indolent prostate cancer at diagnosis is difficult. Of this study was to evaluate the accuracy of current AS protocols in identifying low risk PCa by comparing the histopathology at biopsy and surgery. A retrospective study was performed on all patients who underwent Radical Prostatectomy (RP) between 2008 and 2012. We identified patients who fulfilled inclusion criteria of five different established AS protocols. Histopathology at biopsy was compared with final surgical histopathology to identify upgrading or upstaging of disease. The biochemical recurrence rate in the cohort was also determined. A total of 59 patients (24%) met criteria of at least one protocol. Sixteen patients (28%) were eligible for AS based on all studied criteria. Overall 24 patients (40.6%) were upgraded in their final histopathology while 12 patients (20%) upstaged from their original TRUS biopsy. Two patients (3%) had PSA failure, both had salvage radiotherapy. There is considerable discrepency in current AS selection criteria which makes it necessary to introduce novel markers to identify indolent disease as a part of AS protocol for PCa.

Understanding the Performance of Active Surveillance Selection Criteria in Diverse Urology Practices

We used data from MUSIC (Michigan Urological Surgery Improvement Collaborative) to evaluate the performance of published selection criteria for active surveillance in diverse urology practice settings. For several active surveillance guidelines we calculated the proportion of men meeting each set of selection criteria who actually entered active surveillance, defined as the sensitivity of the guideline. After identifying the most sensitive guideline for the entire cohort we compared demographic and tumor characteristics between patients who met this guideline and entered active surveillance, and those who received initial definitive therapy. Of 4,882 men with newly diagnosed prostate cancer 18% underwent active surveillance. When applied to the entire cohort, the sensitivity of published guidelines ranged from 49% in Toronto to 62% at Johns Hopkins. At apractice level the sensitivity of Johns Hopkins criteria varied widely from 27% to 84% (p <0.001). Compared with men undergoing active surveillance, those meeting Johns Hopkins criteria who received definitive therapy were younger (p<0.001) and more likely to have a positive family history (p = 0.003), lower prostate specific antigen (p <0.001), a greater number of positive cores (2 vs 1) on biopsy (p <0.001) and a higher cancer volume in positive core(s) (p = 0.002). The sensitivity of published active surveillance selection criteria varies widely across diverse urology practices. Among patients meeting the most stringent criteria those who received initial definitive therapy had characteristics suggesting greater cancer risk, underscoring the nuanced clinical factors that influence treatment decisions.

Magnetic Resonance Imaging Targeted Biopsy Improves Selection of Patients Considered for Active Surveillance for Clinically Low Risk Prostate Cancer Based on Systematic Biopsies

Current selection criteria for active surveillance based on systematic biopsy underestimate prostate cancer volume and grade. We investigated the role of additional magnetic resonance imaging targeted biopsy in reclassifying patients eligible for active surveillance based on systematic biopsy. We performed a study at 2 institutions in a total of 281 men with increased prostate specific antigen. All men met certain criteria, including 1) prebiopsy magnetic resonance imaging, 12-core transrectal systematic biopsy and 2 additional magnetic resonance imaging targeted biopsies of lesions suspicious for cancer during the same sequence as systematic biopsy, and 2) eligibility for active surveillance based on systematic biopsy results. Criteria for active surveillance were prostate specific antigen less than 10 ng/ml, no Gleason grade 4/5, 5 mm or less involvement of any biopsy core and 2 or fewer positive systematic biopsy cores. Patient characteristics were compared between reclassified and nonreclassified groups based on magnetic resonance imaging targeted biopsy results. On magnetic resonance imaging 58% of the 281 patients had suspicious lesions. Magnetic resonance imaging targeted biopsy was positive for cancer in 81 of 163 patients (50%). Of 281 patients 28 (10%) were reclassified by magnetic resonance imaging targeted biopsy as ineligible for active surveillance based on Gleason score in 8, cancer length in 20 and Gleason score plus cancer length in 9. Suspicious areas on magnetic resonance imaging were in the anterior part of the prostate in 15 of the 28 men (54%). Reclassified patients had a smaller prostate volume (37 vs 52 cc) and were older (66.5 vs 63 years) than those who were not reclassified (p < 0.05). Magnetic resonance imaging targeted biopsy reclassified 10% of patients who were eligible for active surveillance based on systematic biopsy. Its incorporation into the active surveillance eligibility criteria may decrease the risk of reclassification to higher stages during followup.

Repeated biopsies in patients with prostate cancer on active surveillance: clinical implications of interobserver variation in histopathological assessment.

To investigate the clinical implications of interobserver variation in the assessment of re-biopsies obtained during active surveillance (AS) of prostate cancer. In all, 107 patients with low-risk prostate cancer with 93 diagnostic biopsy sets and 109 re-biopsy sets were included. The International Society of Urological Pathology 2005 Gleason scoring system was used for the histopathological assessment of all biopsies. Three different definitions of histopathological progression were applied. Unweighted and linear weighted Kappa (κ) statistics were used to compare the interobserver agreement. The overall Gleason score agreement was 68.8% with a weighted κ of 0.670. The interobserver agreement was 79.6% for meeting the AS selection criteria. According to the three progression definitions applied, overall agreement was between 80.7% and 89.0% with weighted κ values of 0.746-0.791. Treatment recommendations would have changed in up to 10.1% (95% confidence interval 5.4-17.7%) of the 109 re-biopsy sets. Kappa statistics showed strong agreement between the histological evaluations. However, up to 10% of patients on AS would receive a different treatment recommendation depending upon which histopathological evaluation of re-biopsies was used for treatment planning.

Editorial Comment

Editorial Comment

International multicentre study examining selection criteria for active surveillance in men undergoing radical prostatectomy

Background:The controversies concerning possible overtreatment of prostate cancer, highlighted by debate over PSA screening, have highlighted active surveillance (AS) as an alternative management option for appropriate men. Regional differences in the underlying prevalence of PSA testing may alter the pre-test probability for high-risk disease, which can potentially interfere with the performance of selection criteria for AS. In a multicentre study from three different countries, we examine men who were initially suitable for AS according to the Toronto and Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, that underwent radical prostatectomy (RP) in regards to:1.the proportion of pathological reclassification(Gleason score ⩾7, ⩾pT3 disease),2.predictors of high-risk disease,3.create a predictive model to assist with selection of men suitable for AS.Methods:From three centres in the United Kingdom, Canada and Australia, data on men who underwent RP were retrospectively reviewed (n=2329). Multivariable logistic regression was performed to identify predictors of high-risk disease. A nomogram was generated by logistic regression analysis, and performance characterised by receiver operating characteristic curves.Results:For men suitable for AS according to the Toronto (n=800) and PRIAS (410) criteria, the rates for upgrading were 50.6, 42.7%, and upstaging 17.6, 12.4%, respectively. Significant predictors of high-risk disease were:•Toronto criteria: increasing age, cT2 disease, centre of diagnosis and number of positive cores.•PRIAS criteria: increasing PSA and cT2 disease.Cambridge had a high pT3a rate (26 vs 12%). To assist selection of men in the United Kingdom for AS, from the Cambridge data, we generated a nomogram predicting high-risk features in patients who meet the Toronto criteria (AUC of 0.72).Conclusion:The proportion of pathological reclassification in our cohort was higher than previously reported. Care must be used when applying the AS criteria generated from one population to another. With more stringent selection criteria, there is less reclassification but also fewer men who may benefit from AS.

Pathologic Findings in Radical Prostatectomy Specimens From Patients Eligible for Active Surveillance With Highly Selective Criteria: A Multicenter Study

To evaluate the pathologic features of surgical specimens after radical prostatectomy in patients with low-risk prostate cancer fulfilling the strictest pathologic selection criteria for active surveillance. Retrospective analysis of 10 785 consecutive radical prostatectomy performed in 10 university hospitals (January 2003 through December 2008). A total of 919 patients fulfilled the following unique and very stringent criteria: T1c, prostate-specific antigen (PSA) <10 ng/mL, a single positive biopsy, tumor length <3 mm, and Gleason score <7. Clinico-biologic and pathologic data at diagnosis and after radical prostatectomy, prostatic and tumor volume, pathologic Gleason score and stage, positive surgical margins, insignificant prostate cancer, and PSA outcomes were recorded. Median age was 63 years. Mean prebiopsy PSA level was 6.2 ng/mL. At radical prostatectomy, Gleason score was upgraded in 34% of patients, including 1.2% Gleason score 8-9. Pathologic stages were pT2 in 87.3%, pT3 in 11.1%, and pT4 in 1.4% of cases. Extraprostatic extension was found in 12.5%. Only 26% of patients had "insignificant" tumors. Biochemical recurrence-free survival at 5 years was 92.3%. There was no significant difference in survival between patients with "significant" and "insignificant" tumors (90.1% vs 93.4%; P = .06). Despite of a stringent selection of patients with low-risk prostate cancer, active surveillance definition included a significant proportion of patients with upstaged (about 12%) and upgraded (about one-third) disease at diagnosis. Only a quarter of active surveillance patients have a pathologically confirmed "insignificant" cancer.