Association of extended core sampling with delayed intervention and pathologic outcomes for active surveillance patients A population-based analysis.

INTRODUCTION: Combined systematic plus targeted biopsy sampling improves detection of clinically significant prostate cancer (PCa). Our objective was to evaluate whether extended core sampling at initial biopsy in active surveillance (AS) patients is associated with subsequent AS discontinuation and pathologic outcomes. METHODS: National Comprehensive Cancer Network (NCCN) low- and favorable-intermediate-risk (FIR) AS patients diagnosed between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) Prostate with Watchful Waiting database. Prostate biopsy sampling was operationalized as: standard (10-12 cores), extended (13-20 cores), or super-extended (21+ cores). Sensitivity analyses using differing cutoffs was performed. Outcomes included delayed definitive intervention (radical prostatectomy [RP]/radiotherapy) and pathologic upgrading and/or downgrading in delayed RP patients. Multivariable logistic regression modelling adjusted for sociodemographic/oncologic variables was performed. RESULTS: This cohort included 42 459 patients (low-risk: 28 411; FIR:14 048); 25-29% and 3-5% of patients underwent extended and super-extended core sampling, respectively, at diagnosis. Extended core sampling was associated with decreased odds of definitive intervention in low (odds ratio [OR] 0.89, p=0.003) and grade group 2 (GG2) FIR (OR 0.83, p=0.002) patients. Super-extended sampling was associated with decreased odds of definitive intervention in prostate-specific antigen (PSA) 10-20 FIR patients (OR 0.65, p=0.02). Super-extended sampling was associated with decreased odds of upgrading to ≥GG2 disease in low-risk (OR 0.45, p=0.032) and to ≥GG3 disease in GG2 FIR patients (OR 0.67, p=0.044). CONCLUSIONS: This population-based analysis demonstrates that extended/super-extended sampling at diagnosis is associated with significantly decreased odds of AS discontinuation and pathologic upgrading in low/FIR AS patients. This highlights the significance of extended tissue sampling at initial biopsy to appropriately risk-stratify AS patients and minimize AS discontinuation rates.

Time from biopsy to radical prostatectomy by race in an equal-access healthcare system: Results from the SEARCH cohort.

BACKGROUND: We previously showed that within an equal-access health system, race was not associated with the time between prostate cancer (PC) diagnosis and radical prostatectomy (RP). However, in the more recent time-period of the study (2003-2007), Black men had significantly longer times to RP. We sought to revisit the question in a larger study population with more contemporary patients. We hypothesized that time from diagnosis to treatment would not differ by race, even after accounting for active surveillance (AS) and the exclusion of men at very low to low risk of PC progression. METHODS: We analyzed data from 5885 men undergoing RP from 1988 to 2017 at eight Veterans Affairs Hospitals from SEARCH. Multiple linear regression was used to compare time from biopsy to RP and to examine the risk of delays (>90 and >180 days) between races. In sensitivity analyses we excluded men deemed to have initially chosen AS based on having >365 days from biopsy to RP and men at very low to low PC risk for progression according to National Comprehensive Cancer Network Clinical Practice Guidelines. RESULTS: At biopsy, Black men (n = 1959) were younger, had lower body mass index, and higher prostate specific antigen levels, (all p < 0.02), compared to White men (n = 3926). Time from biopsy to RP was longer in Black men (mean days: 98 vs. 92; adjusted ratio of mean number of days, 1.07 [95% confidence interval: 1.03-1.11], p < 0.001); however, there were no differences in delays >90 or >180 days after adjusting for confounders (all p ≥ 0.286). Results were similar following the exclusion of men potentially under on AS and at very low and low risk. CONCLUSIONS: In an equal-access healthcare system, we did not find evidence of clinically relevant differences in time from biopsy to RP in Black versus White men.

Pathologic upgrading in favorable intermediate risk active surveillance patients: Clinical heterogeneity and implications for active surveillance decision.

INTRODUCTION: Current guidelines support active surveillance (AS) for select patients with favorable intermediate risk (FIR) prostate cancer (CaP). A significant proportion of FIR CaP patients undergoing surgical treatment are found to have evidence of adverse pathology. Our objective was to determine the incidence and predictors of pathologic upgrading in FIR AS patients undergoing radical prostatectomy. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting (WW) database was used to identify men younger than 80 years with National Comprehensive Cancer Network FIR CaP initially opting for AS and/or WW between 2010 and 2015 and subsequently underwent radical prostatectomy at least one year following diagnosis. Patients were assigned into one of three subgroups based on their intermediate risk factor: Gleason Score 7(3 + 4) (Group 1), prostate specific antigen level of 10-20 ng/ml (Group 2), and cT2b-c (Group 3). Pathologic upgrading was present in Group 1 if pathologic GS was 7 (4 + 3) or worse. For patients in Groups 2 and 3, upgrading occurred if pathologic GS was 7 (3 + 4) or worse. Oncologic and sociodemographic predictors of pathologic upgrading were evaluated univariable and multivariable logistic regression analysis. RESULTS: 18,760 patients were identified. Pathologic upgrading occurred in 138 (13.3%), 59 (25.0%), and 8,011 (45.8%) patients in groups 1, 2, and 3 respectively. Pathologic downgrading occurred in 226 (21.7%) patients in group 1. Significant predictors of pathologic upgrading on multivariable analysis included older age at diagnosis: 70 to 79 vs. 40 to 49 years (Groups 1 and 3, P < 0.05), a more recent diagnosis: 2014 to2015 vs. 2010-2011 (Groups 2 and 3, P < 0.005), higher volume disease: 37.5% to 49.9% vs. 0% to 12.4% (Groups 2 and 3, P < 0.005), and clinically palpable disease (Groups 1 and 2, P < 0.05). Additional risk factors for upgrading included uninsured or Medicaid status, diagnosis in a Western region (Group 2), African American ethnicity and higher socioeconomic status (Group 3) CONCLUSIONS: FIR CaP is a clinically heterogeneous risk group with incidence of pathologic upgrading ranging from 13.3% in those with GS 7 (3 + 4) to 45.8% in those with cT2b-c disease. Risk of pathologic upgrading in FIR CaP patients initially managed with AS and/or WW is significantly associated with multiple patient-level oncologic and sociodemographic variables.

Assessing patient risk from cancer and COVID-19: Managing patient distress.

The rapid spread of coronavirus disease 2019 (COVID-19) beginning in Spring 2020 necessitated significant changes to day-to-day interactions in society, as well as to the practice of medicine. Particularly in patients with cancer, these changes can exacerbate the pre-existing psychological stress associated with cancer diagnosis and treatment. We performed a narrative review, encompassing changes to cancer care as a result of COVID-19, the psychological effects of treatment delays, and strategies to mitigate these effects. A number of review articles and guideline bodies have provided guidance on patients for whom treatment may be safely delayed, including low-risk bladder, prostate and kidney tumors, as well as intermediate and high-risk prostate cancer. Mental health diagnoses are prevalent in patients with genitourinary malignancies. Evidence regarding psychologic effects of deferred treatment is limited to those with low risk of disease related morbidity. In this population, psychologic distress attenuated with time. However, in the COVID-19 context, patients with advanced disease are particularly prone to psychologic distress, as are women and younger patients. Strategies to mitigate this distress are emerging and center on recognition from the treating oncologist with appropriate referral as necessary to psycho-oncology providers and engagement of peer-supports. The COVID-19 pandemic has reshaped social structures and health care delivery. For patients with genitourinary malignancies, this may be associated with significant distress, particularly among those with advanced disease and those undergoing active treatment. Physicians treating these patients need to be aware of the psychologic stress the combined effects of the COVID-19 pandemic, cancer diagnosis, and cancer treatment can have and make appropriate referrals to support the holistic care of their patients.

Clinical-genomic Characterization Unveils More Aggressive Disease Features in Elderly Prostate Cancer Patients with Low-grade Disease.

BACKGROUND: Over 20% of men diagnosed with prostate cancer (PC) are ≥75 yr old. More objective disease-specific indices for predicting outcomes beyond chronological age are necessary. OBJECTIVE: To analyze age-related differences in clinical-genomic prognostic features of aggressiveness in localized PC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter cross-sectional study reported the use of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) guidelines. Clinical-genomic data of patients who underwent a prostate biopsy or radical prostatectomy (RP) were obtained from the Decipher Genomic Resource Information Database (NCT02609269). INTERVENTION: Our analyses focused on the 22-gene Decipher genomic classifier (GC) and 50-gene (PAM50) models in the biopsy and RP cohorts stratified by age. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the impact of age on GC scores and PAM50 molecular subtypes. Prognostic indices including Decipher GC scores, PAM50 molecular subtypes, National Comprehensive Cancer Network risk categories, and ISUP grade groups (IGGs) were stratified by age using multivariable logistic regression analyses. RESULTS AND LIMITATIONS: Within histological low-risk IGGs, there were a higher proportion of patients with high-risk Decipher biopsy scores with age (age <60 yr: 10.1% IGG 1 and 29.9% IGG 2 vs age ≥80 yr: 22% IGG 1 and 37.7% IGG 2). The prevalence of the adverse phenotype luminal B (PAM50-defined) increased with age (age <60 yr: 22.7% and 40.2% vs age ≥80 yr: 29.7% and 49.1%, in patients with IGG 1 and IGG 2, respectively). In IGGs 3-5, no age differences were observed. Multivariable models demonstrated that each age decile entailed a 19% (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.10-1.29, p < 0.001) and a 10% (OR 1.1, 95% CI 1.05-1.16) increased probability for a high-risk Decipher biopsy and RP score, respectively. Aside from an obvious selection bias, data on race, family history, prostate volume, and long-term follow-up outcomes were unavailable. CONCLUSIONS: These data demonstrated that elderly men with favorable pathology (IGG 1-2), might harbor more aggressive disease than younger patients based on validated GC scores. PATIENT SUMMARY: The presented clinical-genomic data demonstrate that elderly patients with low-risk prostate cancer might harbor more aggressive disease than their younger counterparts. This suggests that standard well-accepted paradigm of elderly prostate cancer patients not being aggressively treated, based solely on their chronological age, might need to be reconsidered.

The Association of Fatty Acid Levels and Gleason Grade among Men Undergoing Radical Prostatectomy.

BACKGROUND: Epidemiological data suggest that omega-6 (ω-6) fatty acids (FAs) may be associated with cancer incidence and/or cancer mortality, whereas ω-3 FAs are potentially protective. We examined the association of the ratio of ω-6 to ω-3 FA (ω-6:ω-3) and individual FA components with pathological results among men with prostate cancer (PCa) undergoing radical prostatectomy. METHODS: Sixty-nine men were included in the study. Components of ω-6 (linoleic acid (LA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA)) and ω-3 (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) were analyzed by liquid chromatography/mass selective detector separation. Logistic regression analysis was performed to determine association of FA with pathological high grade (Gleason ≥4+3) disease. RESULTS: The were 35 men with low grade disease (Gleason ≤3+4) and 34 men with high grade disease. Men with low grade disease were significantly younger (58y vs 61y, p = 0.012) and had lower D'Amico clinical classification (p = 0.001) compared to men with high grade disease. There was no significant association of ω-6:ω-3 with high grade disease (OR 0.93, p = 0.78), however overall ω-6, ω-3, and individual components of ω-6 and ω-3 FAs except EPA were significantly associated with high grade disease (ω-6: OR 3.37, 95% CI: 1.27,8.98; LA: OR 3.33, 95% CI:1.24,8.94; AA: OR 2.93, 95% CI:1.24,6.94; DGLA: OR 3.21, 95% CI:1.28,8.04; ω-3: OR 3.47, 95% CI:1.22,9.83; DHA: OR 3.13, 95% CI:1.26,7.74). ω-6 and ω-3 FA components were highly correlated (Spearman ρ = 0.77). CONCLUSION: Higher levels of individual components of ω-6 and ω-3FAs may be associated with higher-grade PCa. IMPACT: Studies into the causative factors/pathways regarding FAs and prostate carcinogenesis may prove a potential association with PCa aggressiveness.

Continent Catheterizable Vesicostomy: An Alternative Surgical Modality for Pediatric Patients With Large Bladder Capacity.

OBJECTIVE: To present a modified technique and early outcomes of a continent catheterizable vesicostomy in pediatric patients with either flaccid neurogenic bladder or intractable voiding dysfunction and large capacity bladder. METHODS: Six patients underwent the procedure from October 2014 to December 2015. A 4-cm Pfannenstiel incision was made, avoiding intraperitoneal dissection. After adequate mobilization, a 2-cm vertical flap at the dome of the bladder was identified and tubularized over a 12Fr catheter with 4-0 vicryl suture. The tubularized flap was then intussuscepted into the bladder with four 4-0 polydioxanone sutures, creating a continent mechanism. The catheterizable channel was then tunneled to the umbilicus, the channel ostomy matured, and the cystotomy closed in two layers. RESULTS: The median patient age was 8 (interquartile range [IQR] 12) years. All patients had urinary dysfunction requiring drainage from etiologies that included Eagle-Barrett syndrome (n = 2), Noonan syndrome (n = 1), Lennox-Gastaut syndrome (n = 1), and Spina bifida (n = 2). Median hospital length of stay was 8 (IQR 3) days. One patient had a superficial wound infection treated with antibiotics, and 1 patient required balloon dilation of the catheterizable channel at 3 months postoperatively, secondary to difficulty self-catheterizing. Five patients were successfully self-catheterizing at last follow-up. Median follow-up was 6 (IQR 5) months and there were no intra- or perioperative complications. CONCLUSION: Continent catheterizable vesicostomy is a novel technique for urinary drainage in patients with large bladder capacity that spares use of the appendix or ileum. Early results are encouraging, providing a catheterizable channel through the umbilicus without urinary leakage between catheterization.

Is clinical stage T2c prostate cancer an intermediate- or high-risk disease?

BACKGROUND: Clinical stage T2c (cT2c) is an indeterminate factor in prostate cancer (PC) risk stratification. According to the D'Amico grouping and American Urological Association guidelines, cT2c is a high risk, whereas the National Comprehensive Cancer Network and the European Urological Association classify cT2c as an intermediate risk. This study assessed whether cT2c tumors without other high-risk factors (clinical stage T2c, not otherwise specified [cT2c-NOS]) behaved as an intermediate or high risk through an analysis of biochemical recurrence (BCR) after radical prostatectomy. METHODS: Two thousand seven hundred fifty-nine men from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database and 12,900 men from Johns Hopkins Hospital (JHH) from 1988-2011 and 1982-2012, respectively, were analyzed. Patients were grouped into low-risk (prostate-specific antigen [PSA] < 10 ng/mL, Gleason sum ≤ 6, and cT1-T2a), intermediate-risk (PSA = 10-20 ng/mL, Gleason sum = 7, or cT2b), and high-risk PC categories (PSA > 20 ng/mL, Gleason sum = 8-10, or cT3). Men with cT2c tumors who were not otherwise at high risk (ie, PSA< 20 ng/mL and Gleason sum < 8) were placed into a separate category termed cT2c-NOS. Associations between cT2c-NOS and intermediate- and high-risk patients and BCR were tested with the log-rank test and Cox proportional analysis models. RESULTS: Ninety-nine men (4%) from SEARCH and 202 men (2%) from JHH had tumors classified as cT2c-NOS. The cT2c-NOS patients had a BCR risk similar to that of the intermediate-risk patients (SEARCH, P = .27; JHH, P = .23) but a significantly lower BCR risk in comparison with the high-risk patients (SEARCH, P < .001; JHH, P < .001). When they were specifically compared with intermediate- and high-risk patients, after adjustments for year and center, cT2c-NOS patients had outcomes comparable to those of intermediate-risk patients (SEARCH, P = .53; JHH, P = .54) but significantly better than those of high-risk patients (SEARCH, P = .003; JHH, P < .001). CONCLUSIONS: Patients with cT2c disease without other high-risk features had outcomes similar to the outcomes of patients with intermediate-risk PC and significantly better than the outcomes of patients with high-risk PC. These findings suggest that men with cT2c disease should be considered to be at intermediate risk.