Intraductal Prostate Cancer Affinity for Lymphatic-Predominant Metastases Through 18F-DCFPyL‒Prostate-Specific Membrane Antigen‒Positron Emission Tomography/CT Scans in Pretreatment Prostate Cancer Patients.

PURPOSE: Intraductal prostate cancer (IDC) is linked to unfavorable oncologic outcomes, marked by distinctive cellular intrinsic pathway changes and intricate immunosuppressive microenvironments that could impact the way cancer spreads. The aim of this study was to determine whether the presence of IDC in prostate biopsy specimens obtained from patients before primary prostate cancer (PCa) treatment is associated with a lymph node metastatic propensity in prostate-specific membrane antigen (PSMA)‒positron emission tomography (PET)/CT. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients undergoing a pretreatment 18F-DCFPyL-PSMA-PET/CT between January 1, 2016, and August 2021 at The Princess Margaret Cancer Centre. Outcomes were presence of any metastasis in the overall cohort, presence of lymphatic vs no metastases, and presence of lymphatic vs bone metastasis among patients who underwent PSMA-PET/CT as PCa primary staging. The associations between IDC presence on the prostate biopsy and the study outcomes were evaluated using univariable and multivariable logistic regression analyses. RESULTS: The cohort consisted of 120 patients. IDC and cribriform pattern were observed in 55 (46%) and 48 (40%) prostate biopsies, respectively. Overall, 52 patients (43%) had evidence of metastasis. Presence of IDC on biopsy was associated with increased odds of overall metastasis (odds ratio: 2.47, 95% CI: 1.09-5.61, P = .03). Of the 52 patients with evidence of metastasis, 41 (79%) had evidence of lymphatic metastasis. Presence of IDC on biopsy was associated with significantly increased odds of lymphatic metastasis vs nonmetastases (odds ratio: 3.03, 95% CI: 1.24-7.40, P = .01). CONCLUSIONS: The identification of IDC morphology in prostate biopsy specimens has been observed to be significantly linked with lymph node metastasis on 18F-DCFPyL-PET/CT imaging in a PCa pretreatment staging setting. We found that presence of IDC in prostate biopsy appears to be a marker for lymph node metastasis on 18F-DCFPyL-PET/CT.

Hysterectomy versus chemotherapy for low-risk non-metastatic gestational trophoblastic neoplasia (GTN): A cost-effectiveness analysis.

OBJECTIVE: Determine the cost-effectiveness for hysterectomy versus standard of care single agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). METHODS: A cost-effectiveness analysis was conducted comparing single agent chemotherapy with hysterectomy using decision analysis and Markov modeling from a healthcare payer perspective in Canada. The base case was a 40-year-old patient with low-risk non-metastatic GTN that completed childbearing. Outcomes were life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and adjusted 2022 costs (CAD). Discounting was 1.5% annually and the time horizon was the patient's lifetime. Model validation included face validity, deterministic sensitivity analyses, and scenario analysis. RESULTS: Mean costs for chemotherapy and hysterectomy arms were $34,507 and $17,363, respectively, while effectiveness measure were 30.37 QALYs and 31.04 LYs versus 30.14 QALYs and 30.82 Lys, respectively. The ICER was $74,526 (USD $54,516) per QALY. Thresholds favoring hysterectomy effectiveness were 30-day hysterectomy mortality below 0.2% and recurrence risk during surveillance above 9.2% (low-risk) and 33.4% (high-risk). Scenario analyses for Dactinomycin and Methotrexate led to similar results. Sensitivity analysis using tornado analysis found the cost to be most influenced by single agent chemotherapy cost and risk of resistance, number of weeks of chemotherapy, and probability of postoperative mortality. CONCLUSION: Compared to hysterectomy, single agent chemotherapy as a first-line treatment costs $74,526 for each additional QALY gained. Given that this cost falls below the accepted $100,000 willingness-to-pay threshold and waitlist limitations within public healthcare systems, these results support the continued use of chemotherapy as standard of care approach for low-risk GTN.

Mesorectal nodal metastasis with seminal vesicle invasion in biochemically recurrent prostate cancer.

OBJECTIVES: To determine the prevalence and predictors of mesorectal lymph node (MLN) metastases on prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in patients with biochemically recurrent prostate cancer (PCa) following radical therapy. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients with biochemical failure following radical prostatectomy or radiotherapy who underwent an 18 F-DCFPyL-PSMA-PET/CT at the Princess Margaret Cancer Centre between December 2018 and February 2021. Lesions with PSMA scores ≥2 were considered positive for PCa involvement (PROMISE classification). Predictors of MLN metastasis were evaluated using univariable and multivariable logistic regression analyses. RESULTS: Our cohort consisted of 686 patients. The primary treatment method was radical prostatectomy and radiotherapy in 528 (77.0%) and 158 patients (23.0%), respectively. The median serum PSA level was 1.15 ng/mL. Overall, 384 patients (56.0%) had a positive scan. Seventy-eight patients (11.3%) had MLN metastasis, with 48/78 (61.5%) having MLN involvement as the only site of metastasis. On multivariable analysis, presence of pT3b disease (odds ratio 4.31, 95% confidence interval 1.44-14.2; P = 0.011) was significantly associated with increased odds of MLN metastasis, whereas surgical factors (radical prostatectomy vs radiotherapy; performance/extent of pelvic nodal dissection), surgical margin positivity, and Gleason Grade were not. CONCLUSIONS: In this study, 11.3% of PCa patients with biochemical failure had MLN metastasis on 18 F-DCFPyL-PET/CT. pT3b disease was associated with 4.31-fold significantly increased odds of MLN metastasis. These findings suggest alternate drainage routes for PCa cells, either via alternate lymphatic drainage from the seminal vesicles themselves or secondary to direct extension from posteriorly located tumours invading the seminal vesicles.

Poly(adenosine diphosphate-ribose) polymerase inhibitor combinations in first-line metastatic castrate-resistant prostate cancer setting: a systematic review and meta-analysis.

OBJECTIVES: To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving a combination of first-line poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARAT) vs placebo/ARAT. MATERIALS AND METHODS: We conducted a systematic review/meta-analysis of all published Phase III randomised controlled trials using EMBASE, MEDLINE, and Cochrane (inception until 6 June 2023). Published full-text manuscripts and conference abstracts were inclusion eligible. Study selection/data extraction were independently performed by two authors. The Cochrane Risk-of-Bias 2 Tool was used, and certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Pooled hazard ratios (HRs) and relative risks, with corresponding confidence intervals (CIs), were generated using random-effects models. RESULTS: Three trials were identified: PROpel, MAGNITUDE, and TALAPRO-2. Compared to placebo/ARAT, the PARPi/ARAT combination was associated with a 35% rPFS improvement in the overall cohort (HR 0.65, 95% CI 0.56-0.76), with 68%, 45%, and 26% improvements in the BReast CAncer gene 1/gene 2 (BRCA1/2)-mutated (BRCA1/2m; P < 0.001), homologous recombination repair-mutated (HRRm; P < 0.001), and non-HRRm cohorts (P = 0.003), respectively. OS data maturity ranged from 31% to 48%, with overall cohort OS data unavailable from MAGNITUDE. The PROpel/TALAPRO-2 pooled analysis demonstrated a 16% OS improvement in the overall cohort (HR 0.84, 95 CI 0.72-0.98; P = 0.02). OS in the HRRm (HR 0.76, 95% CI 0.61-0.95) and the BRCA1/2m cohorts (HR 0.53, 95% CI 0.18-1.56) were improved, with a higher effect magnitude compared to the overall cohort. This combination was associated with a 45% relative risk increase in Grade ≥3 TEAEs, including 6.22-fold for Grade ≥3 anaemia (31.9% vs 4.9%). CONCLUSIONS: The addition of PARPi to ARAT in the first-line mCRPC setting is associated with rPFS benefits across subgroups, with the greatest magnitude of benefit in BRCA1/2m patients. OS benefits remain inconsistent irrespective of HRRm status, with significant increases in Grade ≥3 TEAEs, particularly anaemia. Currently, we suggest this combined approach be selectively offered to HRRm patients, preferentially BRCA1/2m.

Prostate cancer mortality rates in low- and favorable intermediate-risk active surveillance patients: a population-based competing risks analysis.

PURPOSE: To determine prostate cancer (PCa) and other-cause mortality rates in low- and favorable intermediate-risk (FIR) active surveillance (AS) patients. METHODS: The SEER Prostate with Watchful Waiting database was used to identify men diagnosed with NCCN low or FIR PCa, between 2010 and 2015, managed with AS. FIR patients were subdivided into three subgroups, based on their intermediate risk factor: grade group two (GG2), PSA 10-20 ng/ml or cT2b-c disease. Cumulative incidence function curves with other-cause mortality as the competing risk were utilized. Predictors of PCa mortality were assessed using multivariable regression analysis with semi-parametric proportional hazards modeling. RESULTS: Among 70,871 patients, 48,127 (67.9%) had low and 22,744 (32.1%) had FIR disease. Median patient age was 64.0 years, and median PSA was 5.70 ng/ml. Median follow-up was 49.0 months. There were 166 (0.2%) PCa and 3,176 (4.48%) other-cause mortalities. The 5-year mortality rates in the low and FIR cohorts overall were 0.29% and 0.28%, respectively (p = 0.64). Within the FIR cohort, the corresponding rates were highest in the PSA 10-20 ng/ml subgroup at 0.73%, followed by 0.32% for GG2 FIR and 0.052% for cT2b-c FIR disease (p < 0.001). Older age at diagnosis (sHR 2.38, p = 0.006), Medicaid insurance (sHR: 2.58, p < 0.001), low socioeconomic (sHR 1.39, p = 0.032), and non-married statuses (sHR: 2.58, p < 0.001) were associated with increased PCa mortality. CONCLUSION: Intermediate-term PCa mortality rates in FIR PCa patients are non-significantly different to those with low-risk PCa. However, there is significant within-group heterogeneity, with PCa mortality rates significantly higher in the PSA 10-20 subgroup.

Suspension of Oncology Randomized Clinical Trials during the COVID-19 Pandemic: A Cross-Sectional Evaluation of COVID-Related Suspensions.

We conducted a cross-sectional analysis of ClinicalTrials.gov-registered oncology randomized controlled trials between September 2019 and December 2021 to identify predictors of trial suspensions. The dataset included 1,183 oncology trials, of which 384 (32.5%) were suspended. COVID-19 accounted for 47 (12.2%) suspensions. Trials that were single center- or US-based had higher odds of COVID-19 (ORs: 3.85 and 2.48, 95% CIs: 1.60-11.50 and 1.28-4.93, respectively) or any-reason suspensions (ORs: 2.33 and 2.04, 95% CIs: 1.46-3.45 and 1.40-2.76, respectively). Phase two (OR 1.27), three (OR 6.45) and four trials (OR 11.5) had increased odds of COVID-19 suspensions, compared to phase one trials.

Transparency of racial participation reporting in randomized controlled trials of minimally invasive surgical techniques.

BACKGROUND: Enrolment of racial/ethnic minorities in randomized controlled trials (RCTs) has historically been poor, despite efforts at improving access to RCTs. Under-representation of racial/ethnic minorities limits the external validity and generalizability of trials. Our objective was to determine to what extent are published RCTs of minimally invasive surgical techniques reporting the racial composition of their study cohorts and to describe the racial composition of patients enrolled in these trials, where data were available. METHODS: EMBASE (OvidSP®), MEDLINE (OvidSP®), and Cochrane (Wiley®) databases were systematically searched from inception to December 22, 2017 to identify all RCTs comparing minimally invasive and classical surgical techniques. The Mann-Kendall trend test was used to evaluate reporting trends over the study period. Predictors of racial reporting were evaluated using logistic regression analyses. RESULTS: Our search strategy yielded 9,321 references of which 496 RCTs met our inclusion/exclusion criteria. Racial information was reported in 20 (4.03%) studies. There was no significant improvement in racial reporting over the study period (p for trend = 0.31). Of the 17 different patient populations accounting for the 20 RCTs, 14 (82.4%) originated from the USA. Multicenter RCTs had significantly increased likelihood of reporting racial composition of the patient cohort (odds ratio 5.10, p = 0.025). White/Caucasian patients accounted for 84.5% of the pooled patient population, with Black/African American, Asian and Latin/Hispanic patients accounting for 7.9%, 1.2%, and 2.1%, respectively. CONCLUSIONS: Among RCTs assessing minimally invasive surgical techniques over the past 30 years, data on included patients' race is poorly reported. In addition to important efforts to improve access to clinical trials for racial and ethnic minorities, efforts aimed at improving reporting and transparency of surgical RCTs are sorely needed.

Combined genetic and epigenetic alterations of the TERT promoter affect clinical and biological behavior of bladder cancer.

In urothelial bladder cancer (UBC), risk stratification remains an important unmet need. Limitless self-renewal, governed by TERT expression and telomerase activation, is crucial for cancer progression. Thus, telomerase activation through the interplay of mutations (TERTpMut ) and epigenetic alterations in the TERT promoter may provide further insight into UBC behavior. Here, we investigated the combined effect of TERTpMut and the TERT Hypermethylated Oncological Region (THOR) status on telomerase activation and patient outcome in a UBC international cohort (n = 237). We verified that TERTpMut were frequent (76.8%) and present in all stages and grades of UBC. Hypermethylation of THOR was associated with higher TERT expression and higher-risk disease in nonmuscle invasive bladder cancers (NMIBC). TERTpMut alone predicted disease recurrence (HR: 3.18, 95%CI 1.84 to 5.51, p < 0.0001) but not progression in NMIBC. Combined THORhigh /TERTpMut increased the risk of disease recurrence (HR 5.12, p < 0.0001) and progression (HR 3.92, p = 0.025). Increased THOR hypermethylation doubled the risk of stage progression of both TERTpwt and TERTpMut NMIBC. These results highlight that both mechanisms are common and coexist in bladder cancer and while TERTpMut is an early event in bladder carcinogenesis THOR hypermethylation is a dynamic process that contributes to disease progression. While the absence of alterations comprises an extremely indolent phenotype, the combined genetic and epigenetic alterations of TERT bring additional prognostic value in NMIBC and provide a novel insight into telomere biology in cancer.

Cancer diagnosis and risk of suicide after accounting for prediagnosis psychiatric care: A matched-cohort study of patients with incident solid-organ malignancies.

BACKGROUND: Previous studies have demonstrated an association between a diagnosis of cancer and the risk of suicide; however, they failed to account for psychiatric care before a cancer diagnosis, which may confound this relationship. The objective of this study was to assess the effect of a cancer diagnosis on the risk of suicide, accounting for prediagnosis psychiatric care utilization. METHODS: All adult residents of Ontario, Canada who were diagnosed with cancer (1 of prostate, breast, colorectal, melanoma, lung, bladder, endometrial, thyroid, kidney, or oral cancer) between 1997 and 2014 were identified. Noncancer controls were matched 4:1 based on sociodemographics, including a psychiatric utilization gradient (PUG) score (with 0 indicating none; 1, outpatient; 2, emergency department; and 3, hospital admission). A marginal, cause-specific hazard model was used to assess the effect of cancer on the risk of suicidal death. RESULTS: Among 676,470 patients with cancer and 2,152,682 matched noncancer controls, there were 8.2 and 11.4 suicides per 1000 person-years of follow-up, respectively. Patients with cancer had an overall higher risk of suicidal death compared with matched patients without cancer (hazard ratio, 1.34; 95% CI, 1.22-1.48). This effect was pronounced in the first 50 months after cancer diagnosis (hazard ratio, 1.60; 95% CI, 1.42-1.81); patients with cancer did not demonstrate an increased risk thereafter. Among individuals with a PUG score 0 or 1, those with cancer were significantly more likely to die of suicide compared with controls. There was no difference in suicide risk between patients with cancer and controls for those who had a PUG score of 2 or 3. CONCLUSIONS: A cancer diagnosis is associated with increased risk of death from suicide compared with the general population even after accounting for precancer diagnosis psychiatric care utilization. The specific factors underlying the observed associations remain to be elucidated.

The impact of psychiatric utilisation prior to cancer diagnosis on survival of solid organ malignancies.

BACKGROUND: Among patients with cancer, prior research suggests that patients with mental illness may have reduced survival. The objective was to assess the impact of psychiatric utilisation (PU) prior to cancer diagnosis on survival outcomes. METHODS: All residents of Ontario diagnosed with one of the top 10 malignancies (1997-2014) were included. The primary exposure was psychiatric utilisation gradient (PUG) score in 5 years prior to cancer: 0: none, 1: outpatient, 2: emergency department, 3: hospital admission. A multivariable, cause-specific hazard model was used to assess the effect of PUG score on cancer-specific mortality (CSM), and a Cox proportional hazard model for effect on all-cause mortality (ACM). RESULTS: A toal of 676,125 patients were included: 359,465 (53.2%) with PUG 0, 304,559 (45.0%) PUG 1, 7901 (1.2%) PUG 2, and 4200 (0.6%) PUG 3. Increasing PUG score was independently associated with worse CSM, with an effect gradient across the intensity of pre-diagnosis PU (vs PUG 0): PUG 1 h 1.05 (95% CI 1.04-1.06), PUG 2 h 1.36 (95% CI 1.30-1.42), and PUG 3 h 1.73 (95% CI 1.63-1.84). Increasing PUG score was also associated with worse ACM. CONCLUSIONS: Pre-cancer diagnosis PU is independently associated with worse CSM and ACM following diagnosis among patients with solid organ malignancies.

Defining a Cohort that May Not Require Repeat Prostate Biopsy Based on PCA3 Score and Magnetic Resonance Imaging: The Dual Negative Effect.

PURPOSE: Prostate cancer over diagnosis and overtreatment are concerns for clinicians and policy makers. Multiparametric magnetic resonance imaging and the PCA3 (prostate cancer antigen 3) urine test select for clinically significant cases. We explored how well the tests performed together with previous biopsies. MATERIALS AND METHODS: In accordance with ethics committee approval we collected clinicopathological data on all patients in whom a PCA3 test was done from January 2011 to June 2016. This included patients on active surveillance for low risk prostate cancer and those without prostate cancer who had previous negative biopsies and suspicion of occult disease. We explored whether age, prostate specific antigen, PCA3 score, multiparametric magnetic resonance imaging, digital rectal examination, family history and prostate size would predict clinically significant prostate cancer on repeat biopsy. The negative predictive value of multiparametric magnetic resonance imaging and PCA3 score was calculated. RESULTS: A total of 470 patients were included in study. The PCA3 score was abnormal at 35 or greater in 32.5% of cases. In the multivariate model including 154 men only age (OR 1.08, 95% CI 1.01-1.16), multiparametric magnetic resonance imaging PI-RADS™ (Prostate Imaging-Reporting and Data System) score 4 (OR 16.6, 95% CI 3.9-70.0) or 5 (OR 28.3, 95% CI 5.7-138) and PCA3 score (OR 2.9, 95% CI 1.0-8.8) predicted clinically significant cancer on biopsy. No patient with negative multiparametric magnetic resonance imaging and a normal PCA3 score had clinically significant prostate cancer on biopsy for a negative predictive value of 100% (p <0.0001). CONCLUSIONS: In patients with dual negative tests (multiparametric magnetic resonance imaging and PCA3 score) clinically significant prostate cancer was never found on biopsy, which may be unnecessary in this group. This study was limited by its retrospective design, selection bias and lack of cost-effectiveness data.

Extended Venous Thromboembolism Prophylaxis after Radical Cystectomy: A Call for Adherence to Current Guidelines.

PURPOSE: Radical cystectomy is inherently associated with morbidity. We assess the timing and incidence of venous thromboembolism, review current guideline recommendations and provide evidence for considering extended venous thromboembolism prophylaxis in all patients undergoing radical cystectomy. MATERIALS AND METHODS: We searched PubMed® for available literature on radical cystectomy and venous thromboembolism, focusing on incidence and timing, evidence supporting extended venous thromboembolism prophylaxis in patients undergoing radical cystectomy or abdominal oncologic surgery, current guideline recommendations, safety considerations and direct oral anticoagulants. Search terms included "radical cystectomy," "venous thromboembolism," "prophylaxis," and "extended oral anticoagulants" and "direct oral anticoagulants" alone and in combination. Relevant articles were reviewed, including original research, reviews and clinical guidelines. References from review articles and guidelines were also assessed to develop a narrative review. RESULTS: The incidence of symptomatic venous thromboembolism in short-term followup after radical cystectomy is 3% to 11.6%, of which more than 50% of cases will occur after hospital discharge. Meta-analyses of clinical trials in patients undergoing major abdominal oncologic operations suggest a decreased risk of venous thromboembolisms for patients receiving extended (4 weeks) venous thromboembolism prophylaxis. Extended prophylaxis should be considered in all radical cystectomy cases. Although the relative risk of bleeding also increases, the overall net benefit of extended prophylaxis clearly favors use for at least 28 days postoperatively. Extrarenal eliminated prophylaxis agents are preferred given the risk of renal insufficiency in radical cystectomy cases, with newer oral anticoagulants providing an alternative route of administration. CONCLUSIONS: Patients undergoing radical cystectomy are at high risk for venous thromboembolism after hospital discharge. There is strong evidence that extended prophylaxis significantly decreases the risk of venous thromboembolism in oncologic surgery cases. Use of extended prophylaxis after radical cystectomy has been poorly adopted, emphasizing the need for better adherence to current urology procedure specific guidelines as extended prophylaxis for radical cystectomy is the standard of care. Specific and rare circumstances may require case by case assessment.

Testosterone Responders to Continuous Androgen Deprivation Therapy Show Considerable Variations in Testosterone Levels on Followup: Implications for Clinical Practice.

PURPOSE: We determined whether men on continuous androgen deprivation therapy who achieve testosterone less than 0.7 nmol/l demonstrate subsequent testosterone elevations during followup and whether such events predict worse oncologic outcomes. MATERIALS AND METHODS: We evaluated a random, retrospective sample of 514 patients with prostate cancer treated with continuous androgen deprivation therapy in whom serum testosterone was less than 0.7 nmol/l at University Health Network between 2007 and 2016. Patients were followed from the date of the first testosterone measurement of less than 0.7 nmol/l to progression to castrate resistance, death or study period end. Study outcomes were the development of testosterone elevations greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, and progression to a castrate resistant state. Survival curves were constructed to determine the rate of testosterone elevations. Multivariate Cox regression analysis was done to assess whether elevations predicted progression to castrate resistance. RESULTS: Median patient age was 74 years and median followup was 20.3 months. Within 5 years of followup 82%, 45% and 18% of patients had subsequent testosterone levels greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, respectively. In 96% to 100% of these patients levels less than 0.7 nmol/l were subsequently reestablished within 5 years. No patient baseline characteristic was associated with elevations and elevations were not a significant predictor of progression to a castrate resistant state. CONCLUSIONS: Men on continuous androgen deprivation therapy in whom initial testosterone is less than 0.7 nmol/l frequently show subsequent elevations in serum testosterone. Such a development should not trigger an immediate response from physicians as these events are prognostically insignificant with regard to oncologic outcomes. Levels are eventually reestablished at less than 0.7 nmol/l.

Evaluation of an Aggressive Prostate Biopsy Strategy in Men Younger than 50 Years.

PURPOSE: Longitudinal cohort studies and guidelines demonstrate that prostate specific antigen 1 ng/ml or greater in younger patients confers an increased risk of delayed prostate cancer death. At our institution we have used an aggressive biopsy strategy in younger patients with prostate specific antigen 1 ng/ml or greater. Our objective was to determine the proportion of detected cancer and specifically clinically significant cancer by this strategy. MATERIALS AND METHODS: The prostate biopsy database at Princess Margaret Cancer Centre was queried for patients younger than 50 years who underwent a first prostate biopsy between 2000 and 2016. We included only patients who underwent prostate biopsy due to prostate specific antigen 1 ng/ml or greater and those with a suspicious digital rectal examination, a positive family history or a suspicious lesion on transrectal ultrasound. All clinical and pathological parameters were analyzed. Patients were stratified according to specific prostate specific antigen values. Multivariable logistic regression was performed to ascertain predictors of any prostate cancer diagnosis and of clinically significant prostate cancer. RESULTS: Of the 199 patients who met study inclusion criteria 37 (19%) were diagnosed with prostate cancer and 8 (22%) had a Gleason score of 7 or greater. Of those diagnosed with prostate cancer 25 (68%) had prostate specific antigen 1.5 ng/ml or greater and all men with a Gleason score of 7 or greater had prostate specific antigen 1.5 ng/ml or greater. Notably 19 patients (51%) had prostate cancer exceeding the Epstein criteria for active surveillance. Factors predicting prostate cancer included a positive family history, rising prostate specific antigen and lower prostate volume. CONCLUSIONS: Our results justify adopting an aggressive prostate biopsy strategy in men younger than 50 years with prostate specific antigen 1.5 ng/ml or greater while patients with prostate specific antigen less than 1.5 ng/ml are unlikely to have significant cancer. Special attention should be given to patients with a smaller prostate and a positive family history.

Limitations in Predicting Organ Confined Prostate Cancer in Patients with Gleason Pattern 4 on Biopsy: Implications for Active Surveillance.

PURPOSE: In prostate cancer biopsy Gleason score predicts stage and helps determine active surveillance suitability. Evidence suggests that small incremental differences in the quantitative percent of Gleason pattern 4 on biopsy stratify disease extent, biochemical failure following surgery and eligibility for active surveillance. We explored the overall quantitative percent of Gleason pattern 4 levels and adverse outcomes in patients with low and intermediate risk prostate cancer to whom active surveillance may be offered under expanded criteria. MATERIALS AND METHODS: We analyzed the records of patients with biopsy Gleason score 6 (3 + 3) or 7 (3 + 4) who underwent radical prostatectomy from January 2008 to August 2015. Age, prostate specific antigen, Gleason score, quantitative percent of Gleason pattern 4, overall percent positive cores (percent of prostate cancer) and clinical stage were explored as predictors of nonorgan confined disease and time to failure after radical prostatectomy. RESULTS: In 1,255 patients biopsy Gleason score 7 (3 + 4) was associated with T3 or greater disease at radical prostatectomy in 35.0% compared with Gleason score 6 (3 + 3) in 19.0% (p <0.001). On multivariate analysis for each quantitative percent of Gleason pattern 4 increase there were 2% higher odds of T3 or greater disease (OR 1.02, 95% CI 1.01-1.04, p <0.001). When stratified, patients with Gleason score 7 (3 + 4) only approximated the pT3 rates of Gleason score 6 (3 + 3) when prostate specific antigen was less than 8 ng/ml and the percent of prostate cancer was less than 15%. In those cases the quantitative percent of Gleason pattern 4 had less effect. Time to failure after radical prostatectomy was worse in Gleason score 7 (3 + 4) than 6 (3 + 3) cases. CONCLUSIONS: The quantitative percent of Gleason pattern 4 helps predict advanced disease and Gleason score 7 (3 + 4) is associated with worse outcomes. However, the impact of the quantitative percent of Gleason pattern 4 on adverse pathological and clinical outcomes is best used in combination with prostate specific antigen, age and disease volume since each has a greater impact on predicting nonorgan confined disease. The calculated absolute risk of T3 or greater can be used in shared decision making on prostate cancer treatment by patients and clinicians.

Development and external validation of a biopsy-derived nomogram to predict risk of ipsilateral extraprostatic extension.

OBJECTIVES: To develop and externally validate a nomogram that predicts risk of side-specific extraprostatic extension (EPE) at time of surgery, using commonly available preoperative markers. MATERIALS AND METHODS: A consecutive sample of 753 men treated by radical prostatectomy (RP) at the University Health Network, Toronto, between 2009 and 2015, was used to develop the nomogram. The validation cohort consisted of 311 men treated by RP at Ottawa Hospital Research Institute, between 1992 and 2014. The study outcome was presence of ipsilateral EPE. The association between predictors considered and EPE was tested using univariate and multivariate logistic regression analyses. The predictive accuracy of the nomogram was determined using the area under the receiver-operating characteristic curve. RESULTS: The overall rate of EPE was 19.8% of all lobes in the developmental cohort and 28.9% in the validation cohort. Significant variables in the models were age, prostate-specific antigen and ipsilateral Gleason score, percentage of positive cores and highest core involvement (all P < 0.05). The nomogram predicting risk of EPE had a predictive accuracy of 0.74 in the external validation cohort. CONCLUSION: We developed and externally validated a nomogram that predicts the risk of ipsilateral EPE based on commonly used preoperative markers. This nomogram may be used to assist surgical decision-making prior to RP.