Limited Relevance of the Very Low Risk Prostate Cancer Classification in the Modern Era: Results from a Large Institutional Active Surveillance Cohort.

Although the American Urological Association recently dropped the very low-risk (VLR) subcategory for low-risk prostate cancer (PCa) and the European Association of Urology does not substratify low-risk PCa, the National Comprehensive Cancer Network (NCCN) guidelines still maintain this stratum, which is based on the number of positive biopsy cores, tumor extent in each core, and prostate-specific antigen density. This subdivision may be less applicable in the modern era in which imaging-targeted prostate biopsies are common practice. In our large institutional active surveillance cohort of patients diagnosed from 2000 to 2020 (n = 1276), the number of patients meeting NCCN VLR criteria decreased significantly in recent years, with no patient meeting VLR criteria after 2018. By contrast, the multivariable Cancer of the Prostate Risk Assessment (CAPRA) score effectively substratified patients over the same period and was predictive of upgrading on repeat biopsy to Gleason grade group ≥2 on multivariable Cox proportional-hazards regression modeling (hazard ratio 1.21, 95% confidence interval 1.05-1.39; p < 0.01), independent of age, genomic test results, and magnetic resonance imaging findings. These findings suggest that the NCCN VLR criteria are less applicable in the targeted biopsy era, and that the CAPRA score or similar instruments are better contemporary risk stratification tools for men on active surveillance. PATIENT SUMMARY: We investigated whether the National Comprehensive Cancer Network classification of very low risk (VLR) for prostate cancer is relevant in the modern era. We found that in a large group of patients on active surveillance, no man diagnosed after 2018 satisfied the VLR criteria. However, the Cancer of the Prostate Risk Assessment (CAPRA) score discriminated patients by cancer risk at diagnosis and was predictive of outcomes on active surveillance, and thus may be a more relevant classification scheme in the modern era.

Post-diagnostic coffee and tea consumption and risk of prostate cancer progression by smoking history.

PURPOSE: Post-diagnostic coffee and tea consumption and prostate cancer progression is understudied. METHODS: We examined 1,557 men from the Cancer of the Prostate Strategic Urologic Research Endeavor who completed a food frequency questionnaire a median of 28 months post-diagnosis. We estimated associations between post-diagnostic coffee (total, caffeinated, decaffeinated) and tea (total, non-herbal, herbal) and risk of prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer death) using Cox proportional hazards regression. We also examined whether smoking (current, former, never) modified these associations. RESULTS: We observed 167 progression events (median follow-up 9 years). Higher coffee intake was associated with higher risk of progression among current smokers (n = 95). The hazard ratio (HR) [95% confidence interval (CI)] for 5 vs 0 cups/day of coffee was 0.5 (CI 0.2, 1.7) among never smokers, but 4.5 (CI 1.1, 19.4) among current smokers (p-interaction: 0.001). There was no association between total coffee intake and prostate cancer progression among never and former smokers. However, we observed an inverse association between decaffeinated coffee (cups/days) and risk of prostate cancer progression in these men (HR > 0 to < 1 vs 0: 1.1 (CI 0.7, 1.8); HR1 to <2 vs 0: 0.7 (CI 0.3, 1.4); HR≥2 vs 0: 0.6 (CI 0.3, 1.1); p-trend = 0.03). There was no association between tea and prostate cancer progression, overall or by smoking status. CONCLUSION: Among non-smoking men diagnosed with localized prostate cancer, moderate coffee and tea consumption was not associated with risk of cancer progression. However, post-diagnostic coffee intake was associated with increased risk of progression among current smokers.

Prostate biopsy histopathologic features correlate with a commercial gene expression assay's reclassification of patient NCCN risk category.

BACKGROUND: For biopsies with Gleason 3 + 3 = 6 or 3 + 4 = 7 prostate cancer, the Genomic Prostate Score (GPS; OncotypeDx) is designed to predict severe pathology at prostatectomy, and, in some cases, recommends reclassification of the National Comprehensive Cancer Network (NCCN) risk category. We hypothesized that certain histopathologic features that were not considered in the original design of the assay actually would be associated with the NCCN risk category change indicated by GPS testing. METHODS: For patients with recommended NCCN risk category change, the biopsy cores used for GPS were re-reviewed for stromal reaction, chronic inflammation, and tumor nuclear polarization. RESULTS: Of 520 patients from May 2011 to December 2018, GPS testing suggested NCCN risk reclassification in 131 (25%); 127 of these slides were available. Of these, the NCCN risk category increased from intermediate to high in 8, low to intermediate in 15, very low to low in 1, and decreased from intermediate to low in 32, and low to very low in 71. Biopsies with NCCN risk increase were associated with moderate or severe stromal reaction (p < .001) and chronic inflammation (p < .001); biopsies with NCCN risk decrease were associated with absence of these features. In Gleason 3 + 3 = 6 cases (n = 93), presence of nuclear polarization was associated with NCCN risk decrease and its absence with increase (p < .001). CONCLUSIONS: Moderate or severe stromal reaction, chronic inflammation, and lack of nuclear polarization in Gleason score 3 + 3 = 6 tumors were each associated with an increase in NCCN risk category indicated by GPS and vice versa. Our results suggest that GPS captures histologic features associated with aggressiveness that are not routinely assessed in standard histopathologic assessments, and that consideration of such histologic features may improve upon current tumor grading approaches.

Genomic Risk Predicts Molecular Imaging-detected Metastatic Nodal Disease in Prostate Cancer.

BACKGROUND: The Decipher genomic classifier (GC) is increasingly being used to determine metastasis risk in men with localized prostate cancer (PCa). Whether GCs predict for the presence of occult metastatic disease at presentation or subsequent metastatic progression is unknown. OBJECTIVE: To determine if GC scores predict extraprostatic 68Ga prostate-specific membrane antigen (68Ga-PSMA-11) positron emission tomography (PET) positivity at presentation. DESIGN, SETTING, AND PARTICIPANTS: Between December 2015 and September 2018, 91 PCa patients with both GC scores and pretreatment 68Ga-PSMA-11 PET scans were identified. Risk stratification was performed using the National Comprehensive Cancer Network (NCCN), Cancer of the Prostate Risk Assessment (CAPRA), and GC scores. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression was used to identify factors correlated with PSMA-positive disease. RESULTS AND LIMITATIONS: The NCCN criteria identified 23 (25.3%) and 68 patients (74.7%) as intermediate and high risk, while CAPRA scores revealed 28 (30.8%) and 63 (69.2%) as low/intermediate and high risk, respectively. By contrast, only 45 patients (49.4%) had high-risk GC scores. PSMA-avid pelvic nodal involvement was identified in 27 patients (29.7%). Higher GC score was significantly associated with pelvic nodal involvement (odds ratio [OR] 1.38 per 0.1 units; p=0.009) and any PSMA-avid nodal involvement (pelvic or distant; OR 1.40 per 0.1 units; p=0.007). However, higher GC score was not significantly associated with PSMA-avid osseous metastases (OR 1.11 per 0.1 units; p=0.50). Limitations include selection bias for patients able to receive both tests and the sample size. CONCLUSIONS: Each 0.1-unit increase in GC score was associated with an approximate 40% increase in the odds of PSMA-avid lymph node involvement. These data suggest that patients with GC high risk might benefit from more nodal imaging and treatment intensification, potentially via pelvic nodal dissection, pelvic nodal irradiation, and/or the addition of chemohormonal agents. PATIENT SUMMARY: Patients with higher genomic classifier scores were found to have more metastatic lymph node involvement on prostate-specific membrane antigen imaging.

Trends in Complementary and Alternative Medicine Use among Patients with Prostate Cancer.

PURPOSE: We explored the prevalence and trends of self-reported complementary and alternative medicine use among patients with prostate cancer using CaPSURE™ (Cancer of the Prostate Strategic Urologic Research Endeavor). MATERIALS AND METHODS: A total of 7,989 CaPSURE participants completed questionnaires between 1996 and 2016 on the use of nearly 70 complementary and alternative medicine types. Participants were defined as users if they indicated that they had ever used complementary and alternative medicines. To evaluate trends among 7,696 patients with newly diagnosed prostate cancer we considered complementary and alternative medicine use within 24 months of diagnosis and calculated the percent change in complementary and alternative medicine use between groups defined by the year of diagnosis. RESULTS: Of patients with prostate cancer 56% reported complementary and alternative medicine use on at least 1 questionnaire. Multivitamin and omega-3 fatty acid use was common at 40% and 24% of patients, respectively. Compared to nonusers greater proportions of complementary and alternative medicine users were college educated, had a higher household income and lived in the West and Midwest. Median prostate specific antigen at diagnosis was 5.8 (IQR 4.4-8.4) and 6.2 ng/ml (IQR 4.7-10.1) among users and nonusers, respectively (p <0.01). Between those diagnosed in 1996 to 2000 and 2011 to 2016, complementary and alternative medicine use increased 128% from 24% to 54%. When comparing participants diagnosed in 2006 to 2010 with those diagnosed in 2011 to 2016, a 108% increase was seen in supplemental vitamin D use and a -48% decrease was seen in supplemental vitamin E use. CONCLUSIONS: Many patients with prostate cancer reported complementary and alternative medicine use. Multivitamins and omega-3 fatty acids were commonly ingested and vitamin D use increased dramatically from 2006 to 2010 compared to 2011 to 2016. These data can guide clinical discussions and decision making such as nutritionist referral and help prioritize future research.

Racial variation in prostate cancer upgrading and upstaging among men with low-risk clinical characteristics.

BACKGROUND: African American (AA) men suffer a higher prostate cancer (PCa) burden than other groups. OBJECTIVE: We aim to determine the impact of race on the risk of upgrading, upstaging, and positive surgical margins (PSM) at radical prostatectomy (RP) among men eligible for active surveillance. DESIGN, SETTING, AND PARTICIPANTS: We studied men with low-risk PCa treated with RP at two centers. Low clinical risk was defined by National Comprehensive Cancer Network criteria. Outcome variables were upgrading, upstaging, and PSMs at surgery. Associations between race and the outcomes were evaluated with logistic regression adjusted for age, relationship status, diagnostic prostate-specific antigen level, percentage of positive biopsy cores, surgical approach, year of diagnosis, and clinical site. RESULTS AND LIMITATIONS: Of 9304 men diagnosed with PCa, 4231 were low risk and underwent RP within 1 yr. Men were categorized as AA (n=273; 6.5%), Caucasian (n=3771; 89.1%), or other racial/ethnic group (Other; n=187; 4.4%). AA men had a significantly younger mean age (58.7 yr; standard deviation: ±7.06), and fewer (85%) were married or had a partner. Upgrading (34%) and upstaging (13%) rates did not significantly differ among the groups. The PSM rate was significantly higher in AA men (31%) than in the Caucasian (21%) and Other (20%) groups (p<0.01). We found an association between race group and PSM rate (p<0.03), with higher odds of PSMs in AA men versus Caucasian men (odds ratio [OR]: 1.64; 95% confidence interval [CI], 1.08-2.47). No statistically significant associations between race and rates of upgrading and upstaging were found. This study was limited by the relatively low proportion of AA men in the cohort. CONCLUSIONS: Among clinically low-risk men who underwent RP, AA men had a higher likelihood of PSMs compared with Caucasian men. We did not find statistically significantly different rates of upgrading and upstaging between the race groups. PATIENT SUMMARY: We analyzed two large groups of men with what appeared to be low-risk prostate cancer based on the initial biopsy findings. The likelihood of finding worse disease (higher grade or stage) at the time of surgery was similar across different racial groups.

Prostate brachytherapy: a descriptive analysis from CaPSURE.

PURPOSE: The purpose of this study was to describe demographic and clinical characteristics in a large disease registry of prostate cancer patients treated with prostate brachytherapy (PB) and to identify factors influencing the use of supplemental external beam (SEB) radiation therapy and choice of isotope. METHODS AND MATERIALS: Data were abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a disease registry of 11,804 men with various stages of prostate cancer. The study population consisted of those men who were diagnosed with prostate cancer between 1990 and 2003, had no prior history of cancer and were treated with PB (alone or with SEB). The influence of patient demographics, disease characteristics, and year of diagnosis on the use of SEB and isotope choice was examined. RESULTS: The study population included 791 men. Six hundred nine men (77%) were treated with PB alone and 182 men (23%) were treated with PB and SEB. Patient demographics were not associated with the use of SEB. Disease characteristics were associated with the use of SEB. Patients treated with PB and SEB had higher pretreatment prostate-specific antigen (PSA), higher T-stage, higher Gleason score, and were more likely to be placed in the high-risk category (all p<0.01). The use of SEB increased over the period studied. In a multivariate analysis, patients diagnosed after 1999 were much more likely to receive SEB after controlling for disease characteristics (PSA, T-stage, Gleason). Likewise, higher clinical PSA (odds ratio [OR]=1.08; 95% confidence interval [CI]: 1.04-1.13), higher biopsy Gleason (OR=3.64; 95% CI: 2.60-5.09), and cT2 vs. cT1 (OR=2.06; 95% CI: 1.22-3.48) were more likely to have PB with SEB than PB alone. Patient demographics differed according to isotope. Compared to men treated with 125)I, men treated with (103)Pd were older, less educated, less wealthy, and less likely to have private insurance. Disease characteristics also differed according to isotope. Compared to men treated with 125I, men treated with 103Pd had higher T-stages, higher Gleason scores, and were more likely to be placed in the intermediate- or high-risk category. The choice of isotope did not change over time. CONCLUSIONS: The use of SEB is associated with disease characteristics. SEB has increased over the period studied. Isotope choice is associated with patient demographics and disease characteristics.