Contemporary Diagnosis of Very Low-risk Prostate Cancer in a Multihospital Health Care System.

The National Comprehensive Cancer Network (NCCN) very low risk (VLR) category for prostate cancer (PCa) represents clinically insignificant disease, and detection of VLR PCa contributes to overdiagnosis. Greater use of magnetic resonance imaging (MRI) and biomarkers before patient selection for prostate biopsy (PBx) reduces unnecessary biopsies and may reduce the diagnosis of clinically insignificant PCa. We tested a hypothesis that the proportion of VLR diagnoses has decreased with greater use of MRI-informed PBx using data from our 11-hospital system. From 2018 to 2023, 351/3197 (11%) men diagnosed with PCa met the NCCN VLR criteria. The proportion of VLR diagnoses did not change from 2018 to 2023 (p = 0.8) despite an increase in the use of MRI-informed PBx (from 49% to 82%; p < 0.001). Of patients who underwent combined systematic and targeted PBx and were diagnosed with VLR disease, cancer was found in systematic PBx regions in 79% of cases and in targeted PBx regions in 31% of cases. When performing both systematic and targeted PBx, prebiopsy MRI-based risk calculators could limit VLR diagnosis by 41% using a risk threshold of >5% for Gleason grade group ≥3 PCa to recommend biopsy; the reduction would be 77% if performing targeted PBx only. These findings suggest that VLR disease continues to account for a significant minority of PCa diagnoses and could be limited by targeted PBx and risk stratification calculators. PATIENT SUMMARY: We looked at recent trends for the diagnosis of very low-risk (VLR) prostate cancer. We found that VLR cancer still seems to be frequently diagnosed despite the use of MRI (magnetic resonance imaging) scans before biopsy. The use of risk calculators to identify men who could avoid biopsy and/or biopsy only for lesions that are visible on MRI could reduce the overdiagnosis of VLR prostate cancer.

Ultrasensitive PSA: rethinking post-surgical management for node positive prostate cancer.

Introduction: Clinicians may offer patients with positive lymph nodes (pN1) and undetectable PSA following surgery for prostate cancer either observation or adjuvant therapy based on AUA, EAU, and NCCN guidelines considering standard PSA detection thresholds of <0.1ng/ml. Here we sought to investigate the outcomes of pN1 patients in the era of ultrasensitive PSA testing. Methods: We queried the Northwestern Electronic Data Warehouse for patients with prostate cancer who were pN1 at radical prostatectomy and followed with ultrasensitive PSA. Patients receiving neoadjuvant treatment were excluded. We compared clinical characteristics including age, race, pre-operative PSA, Gleason grade, tumor stage, surgical margins, and nodal specimens to identify factors associated with achievement and maintenance of an undetectable PSA (defined as <0.01 ng/mL). Statistics were performed using t-test, Mann-Whitney U test, chi-squared analysis, and logistic regression with significance defined as p<0.05. Results: From 2018-2023, 188 patients were included. Subsequently, 39 (20.7%) had a PSA decline to undetectable levels (<0.01 ng/mL) post-operatively at a median time of 63 days. Seven percent of these men (3/39) were treated with adjuvant RT + ADT with undetectable PSA levels. 13/39 (33.3%) had eventual rises in PSA to ≥0.01 ng/mL for which they underwent salvage RT with ADT. Overall, 23/39 (59%) patients achieved and maintained undetectable PSA levels without subsequent therapy at median follow-up of 24.2 mo. Compared to patients with PSA persistence after surgery or elevations to detectable levels (≥0.01 ng/mL), patients who achieved and maintained undetectable levels had lower Gleason grades (p=0.03), lower tumor stage (p<0.001), fewer positive margins (p=0.02), and fewer involved lymph nodes (p=0.02). On multivariable analysis, only primary tumor (pT) stage was associated with achieving and maintaining an undetectable PSA; pT3b disease was associated with a 6.6-fold increased chance of developing a detectable PSA (p=0.03). Conclusion: Ultrasensitive PSA can aid initiation of early salvage therapy for lymph node positive patients after radical prostatectomy while avoiding overtreatment in a significant subset. 20% of patients achieved an undetectable PSA and over half of this subset remained undetectable after 2 years.

Implementation of PSMA PET/CT and alignment of ordering to SNMMI appropriate use criteria in a large network system.

INTRODUCTION: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides appropriate use criteria (AUC) for prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) which include guidance on imaging in newly diagnosed prostate cancer and in patients with biochemically recurrent (BCR) disease. This study aims to examine trends in PSMA implementation and the prevalence and outcomes of scans ordered in scenarios deemed rarely appropriate or not meeting SNMMI AUC. METHODS: We retrospectively identified patients who were diagnosed with presumptive National Comprehensive Cancer Network unfavorable intermediate, high, or very high risk prostate cancer, patients who underwent staging for BCR, and all patients staged with PSMA between July 2021 and March 2023. Positivity was validated by adherence to a predetermined reference standard. RESULTS: The frequency of PSMA use increased in initial staging from 24% to 80% and work-up of BCR from 91% to 99% over our study period. In addition, 5% (17/340) of PSMA scans ordered for initial staging did not meet AUC and 3% (15/557) of posttreatment scans were deemed rarely appropriate. Initial staging orders not meeting SNMMI AUC resulted in no positivity (0/17), while rarely appropriate posttreatment scans were falsely positive in 75% (3/4) of cases. Urologists (53%, 17/32) comprised the largest ordering specialty in rarely appropriate use. CONCLUSION: The frequency of PSMA use rose across the study period. A significant minority of patients received PSMA PET/CT in rarely appropriate scenarios yielding no positivity in initial staging and significant false positivity post-therapy. Further education of providers and electronic medical record-based interventions could help limit the rarely appropriate use of PET imaging.

Comparison of Magnetic Resonance Imaging-Based Risk Calculators to Predict Prostate Cancer Risk.

Importance: Magnetic resonance imaging (MRI)-based risk calculators can replace or augment traditional prostate cancer (PCa) risk prediction tools. However, few data are available comparing performance of different MRI-based risk calculators in external cohorts across different countries or screening paradigms. Objective: To externally validate and compare MRI-based PCa risk calculators (Prospective Loyola University Multiparametric MRI [PLUM], UCLA [University of California, Los Angeles]-Cornell, Van Leeuwen, and Rotterdam Prostate Cancer Risk Calculator-MRI [RPCRC-MRI]) in cohorts from Europe and North America. Design, Setting, and Participants: This multi-institutional, external validation diagnostic study of 3 unique cohorts was performed from January 1, 2015, to December 31, 2022. Two cohorts from Europe and North America used MRI before biopsy, while a third cohort used an advanced serum biomarker, the Prostate Health Index (PHI), before MRI or biopsy. Participants included adult men without a PCa diagnosis receiving MRI before prostate biopsy. Interventions: Prostate MRI followed by prostate biopsy. Main Outcomes and Measures: The primary outcome was diagnosis of clinically significant PCa (grade group ≥2). Receiver operating characteristics for area under the curve (AUC) estimates, calibration plots, and decision curve analysis were evaluated. Results: A total of 2181 patients across the 3 cohorts were included, with a median age of 65 (IQR, 58-70) years and a median prostate-specific antigen level of 5.92 (IQR, 4.32-8.94) ng/mL. All models had good diagnostic discrimination in the European cohort, with AUCs of 0.90 for the PLUM (95% CI, 0.86-0.93), UCLA-Cornell (95% CI, 0.86-0.93), Van Leeuwen (95% CI, 0.87-0.93), and RPCRC-MRI (95% CI, 0.86-0.93) models. All models had good discrimination in the North American cohort, with an AUC of 0.85 (95% CI, 0.80-0.89) for PLUM and AUCs of 0.83 for the UCLA-Cornell (95% CI, 0.80-0.88), Van Leeuwen (95% CI, 0.79-0.88), and RPCRC-MRI (95% CI, 0.78-0.87) models, with somewhat better calibration for the RPCRC-MRI and PLUM models. In the PHI cohort, all models were prone to underestimate clinically significant PCa risk, with best calibration and discrimination for the UCLA-Cornell (AUC, 0.83 [95% CI, 0.81-0.85]) model, followed by the PLUM model (AUC, 0.82 [95% CI, 0.80-0.84]). The Van Leeuwen model was poorly calibrated in all 3 cohorts. On decision curve analysis, all models provided similar net benefit in the European cohort, with higher benefit for the PLUM and RPCRC-MRI models at a threshold greater than 22% in the North American cohort. The UCLA-Cornell model demonstrated highest net benefit in the PHI cohort. Conclusions and Relevance: In this external validation study of patients receiving MRI and prostate biopsy, the results support the use of the PLUM or RPCRC-MRI models in MRI-based screening pathways regardless of European or North American setting. However, tools specific to screening pathways incorporating advanced biomarkers as reflex tests are needed due to underprediction.

Prostate Cancer Detection Rate of Transperineal Prostate Biopsy: Cognitive vs Software Fusion, A Multicenter Analysis.

OBJECTIVE: To compare clinically significant prostate cancer detection with TP-TBx utilizing software vs cognitive fusion. It is established that MRI prior to prostate biopsy improves detection of clinically significant cancer (csPCa, Grade Group ≥2). MRI/US fusion targeted biopsy via a transperineal approach (TP-TBx) is increasing in utilization due to the clean percutaneous approach that greatly reduces postbiopsy infection. However, the comparative effectiveness of formal software fusion over cognitive fusion remains under studied. MATERIALS AND METHODS: We performed a retrospective multicenter study from June 2020 to July 2022 including age, race, prostate-specific antigen (PSA), prostate volume, PI-RADS, lesion size(s), number of cores sampled, indication (elevated PSA, prior negative, active surveillance) and anesthesia type. Surgeon preference determined use of cognitive (PrecisionPoint) vs software fusion techniques. Multivariable logistic regression determined factors associated with TP-TBx detection of csPCa. RESULTS: We identified 490 patients (201 cognitive, 289 software fusion) who underwent TP-TBx. Patient age, PSA, number of targets, and PI-RADS were similar (all P > .05). Software fusion TP-TBx had 4 [95% confidence interval (CI) 3-5] more (estimated median difference) systematic cores sampled. csPCa was detected in 44% of all patients. In adjusted analysis, cognitive vs software fusion was similar in detection of csPCa (odds ratio 1.46, 95% CI 0.82-2.58). CONCLUSION: Cognitive vs software fusion TP-TBx has similar csPCa detection, despite fewer systematic cores taken with cognitive fusion. The expense, additional time requirement, and similar outcomes of software fusion platforms confers higher value to cognitive TP-Bx.

A novel prostate cancer subtyping classifier based on luminal and basal phenotypes.

BACKGROUND: Prostate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression-based subtyping model based on prostate-specific biological processes was sought. METHODS: Unsupervised machine learning of gene expression profiles from prospectively collected primary prostate tumors (training, n = 32,000; evaluation, n = 68,547) was used to create a prostate subtyping classifier (PSC) based on basal versus luminal cell expression patterns and other gene signatures relevant to PCa biology. Subtype molecular pathways and clinical characteristics were explored in five other clinical cohorts. RESULTS: Clustering derived four subtypes: luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), and basal neuroendocrine (BN). LP and LD tumors both had higher androgen receptor activity. LP tumors also had a higher expression of cell proliferation genes, MYC activity, and characteristics of homologous recombination deficiency. BI tumors possessed significant interferon γactivity and immune infiltration on immunohistochemistry. BN tumors were characterized by lower androgen receptor activity expression, lower immune infiltration, and enrichment with neuroendocrine expression patterns. Patients with LD tumors had less aggressive tumor characteristics and the longest time to metastasis after surgery. Only patients with BI tumors derived benefit from radiotherapy after surgery in terms of time to metastasis (hazard ratio [HR], 0.09; 95% CI, 0.01-0.71; n = 855). In a phase 3 trial that randomized patients with metastatic PCa to androgen deprivation with or without docetaxel (n = 108), only patients with LP tumors derived survival benefit from docetaxel (HR, 0.21; 95% CI, 0.09-0.51). CONCLUSIONS: With the use of expression profiles from over 100,000 tumors, a PSC was developed that identified four subtypes with distinct biological and clinical features. PLAIN LANGUAGE SUMMARY: Prostate cancer can behave in an indolent or aggressive manner and vary in how it responds to certain treatments. To differentiate prostate cancer on the basis of biological features, we developed a novel RNA signature by using data from over 100,000 prostate tumors-the largest data set of its kind. This signature can inform patients and physicians on tumor aggressiveness and susceptibilities to treatments to help personalize cancer management.

Optimizing detection of clinically significant prostate cancer through nomograms incorporating mri, clinical features, and advanced serum biomarkers in biopsy naïve men.

PURPOSE: To develop nomograms that predict the detection of clinically significant prostate cancer (csPCa, defined as ≥GG2 [Grade Group 2]) at diagnostic biopsy based on multiparametric prostate MRI (mpMRI), serum biomarkers, and patient clinicodemographic features. MATERIALS AND METHODS: Nomograms were developed from a cohort of biopsy-naïve men presenting to our 11-hospital system with prostate specific antigen (PSA) of 2-20 ng/mL who underwent pre-biopsy mpMRI from March 2018-June 2021 (n = 1494). The outcomes were the presence of csPCa and high-grade prostate cancer (defined as ≥GG3 prostate cancer). Using significant variables on multivariable logistic regression, individual nomograms were developed for men with total PSA, % free PSA, or prostate health index (PHI) when available. The nomograms were both internally validated and evaluated in an independent cohort of 366 men presenting to our hospital system from July 2021-February 2022. RESULTS: 1031 of 1494 men (69%) underwent biopsy after initial evaluation with mpMRI, 493 (47.8%) of whom were found to have ≥GG2 PCa, and 271 (26.3%) were found to have ≥GG3 PCa. Age, race, highest PIRADS score, prostate health index when available, % free PSA when available, and PSA density were significant predictors of ≥GG2 and ≥GG3 PCa on multivariable analysis and were used for nomogram generation. Accuracy of nomograms in both the training cohort and independent cohort were high, with areas under the curves (AUC) of ≥0.885 in the training cohort and ≥0.896 in the independent validation cohort. In our independent validation cohort, our model for ≥GG2 prostate cancer with PHI saved 39.1% of biopsies (143/366) while only missing 0.8% of csPCa (1/124) with a biopsy threshold of 20% probability of csPCa. CONCLUSIONS: Here we developed nomograms combining serum testing and mpMRI to help clinicians risk stratify patients with elevated PSA of 2-20 ng/mL who are being considered for biopsy. Our nomograms are available at https://rossnm1.shinyapps.io/MynMRIskCalculator/ to aid with biopsy decisions.

Utilization of genetic testing in men with advanced prostate cancer.

BACKGROUND: Genetic evaluation of men with advanced prostate cancer is recognized as imperative both to guide treatment decisions and to trigger cascade genetic testing of family members. Here we investigate utilization patterns of genetic testing among a contemporary cohort of men with advanced prostate cancer at our institution. METHODS: We queried the Northwestern Electronic Data Warehouse from January 2021 to present for all men diagnosed with National Comprehensive Cancer Network high-risk/very high-risk, regional, or metastatic prostate cancer. Patients were excluded from analyses if treated at an outside institution and/or presented for a second opinion evaluation. Statistics were performed using t-test, Chi-squared test, and univariable and multivariable logistic regression with significance defined as p < 0.05. RESULTS: Atotal of 320 men (52.5%) had local/regional disease and 290 (47.5%) had metastatic disease, 53 (18.3%) of whom had castrate resistant prostate cancer. Rates of germline genetic testing rate were low in patients with localized disease (9.4%) and metastatic disease (34.1%). Only 19 (35.8%) men diagnosed with metastatic castrate resistant prostate cancer underwent germline genetic evaluation. Germline testing was most frequently discussed or ordered by medical oncologists (52%) followed by urologists (20%). Men who underwent germline testing were younger (p < 0.001), more likely to have Medicaid or private insurance (p = 0.002), and more likely to have metastatic disease (p < 0.001). There were no statistically significant differences in baseline PSA, ethnicity, race, or castration sensitivity status. Age (odds ratio [OR]: 0.94, 95% confidence interval [CI]: 0.91-0.97, p < 0.001) and metastatic disease (OR: 5.71, 95% CI: 3.63-9.22, p < 0.001) were significant independent predictors of genetic testing on multivariable logistic regression. CONCLUSIONS: Here we report that utilization of genetic testing is associated with metastatic disease and inversely associated with age. Overall, utilization rates of genetic testing remain low in all patient groups, including in the metastatic castrate resistant setting, where genetic testing can identify patients with homologous recombination repair deficiency who may benefit from use of targeted therapeutics such as PARP inhibitors. Genetic testing in men with aggressive prostate cancer is critical and barriers to routine implementation of testing require further study to develop strategies to improve utilization rates.

Real-world use of MRI for risk stratification prior to prostate biopsy.

BACKGROUND: The utilization of MRI to risk stratify elevated PSA prior to prostate biopsy has been inconsistently adopted and varies considerably by practice setting. This study aims to evaluate the usage and performance of MRI as an advanced risk stratification tool of elevated PSA prior to biopsy and identify factors associated with differential utilization of MRI at a large academic setting with ready access to 3T multiparametric MRI of the prostate. METHODS: A retrospective single-center study of 2900 men presenting with elevated PSA 2-20 ng/mL from 2018 through 2021 was conducted. We analyzed trends in MRI utilization and outcomes of prostate biopsy by MRI usage. Univariate and multivariate logistic regressions were performed to calculate odds ratios to identify patient- and provider-level predictors of MRI usage. RESULTS: Rates of prebiopsy MRI utilization increased from 56% in 2018 to 89% in 2021 (p < 0.001). Prebiopsy MRI led to biopsy avoidance in 31% of men. MRI usage enhanced detection of clinically significant prostate cancer by 13% and reduced identification of Gleason Grade Group 1 disease by 3% and negative biopsies by 10% (p < 0.001). Men who received MRI were more likely to be younger than 75 years in age and have private or Medicare insurance, PSA >4 ng/mL, and PHI >27. In both univariate and multivariate analysis, black race and Medicaid insurance were associated with reduced MRI utilization (all p < 0.001). Urologic provider was an independent predictor of MRI usage (p < 0.001). CONCLUSIONS: Use of MRI as a risk stratification tool for elevated PSA rose during this 4-year study period. Men who self-identify as black or men with Medicaid coverage have diminished rates of MRI usage. Considerable provider-level variability in MRI use was observed. Future research aimed at identifying factors affecting implementation of MRI as a routine risk assessment tool is warranted.

A transcriptomic model for homologous recombination deficiency in prostate cancer.

BACKGROUND: Tumors with mutations associated with homologous recombination deficiency (HRD) are uncommon in prostate cancer (PCa) and variably responsive to PARP inhibition. To better identify tumors with HRD, we developed a transcriptomic signature for HRD in PCa (HRD-P). METHODS: By using an established mutational signature, we created and validated HRD-P in six independent PCa cohorts (primary PCa, n = 8224; metastatic castration-resistant PCa [mCRPC], n = 328). Molecular and clinical features were compared between HRD-P+ tumors and those with single HR-gene mutations. RESULTS: HRD-P+ tumors were more common than tumors with single HR-gene mutations in primary (201/491, 41% vs 32/491 6.5%) and mCRPC (126/328, 38% vs 82/328, 25%) cases, and HRD-P+ was more predictive of genomic instability suggestive of HRD. HRD-P+ was associated with a shorter time to recurrence following surgery and shorter overall survival in men with mCRPC. In a prospective trial of mCRPC treated with olaparib (n = 10), all three men with HRD-P+ experienced prolonged (>330 days) PSA progression-free survival. CONCLUSION: These results suggest transcriptomics can identify more patients that harbor phenotypic HRD than single HR-gene mutations and support further exploration of transcriptionally defined HRD tumors perhaps in conjunction with genomic markers for therapeutic application.

Efficacy and Adverse Events of Docetaxel for Metastatic, Hormone-sensitive Prostate Cancer Among Elderly Men: A Post Hoc Analysis of the CHAARTED Trial.

BACKGROUND: Combination therapy with docetaxel and androgen deprivation therapy (ADT) prolongs overall survival (OS) in men with metastatic hormone-sensitive prostate cancer. We assessed the benefits and adverse effects of docetaxel and ADT in relation to advancing age. METHODS: We performed a post hoc analysis of the CHAARTED trial comparing docetaxel and ADT vs. ADT alone (n = 773). Patients were stratified in age groups <60, 60-70, and >70 years old. Multivariable-adjusted progression-free survival (PFS) and OS were assessed using Kaplan-Meier curves and compared using multivariable Cox regressions with calculated interaction terms between age group and treatment arm. In the combination arm, the incidence of ≥1 adverse event (grade ≥3) and the number of adverse events per patient were compared for each age group using multivariable logistic and linear regressions, respectively. RESULTS: After adjusting for clinical variables, docetaxel's effect did not vary by age group for PFS and OS. There was no significant difference in the odds ratio of ≥1 adverse event (P > .1 for age groups 60-70 and >70 years old compared with <60 years old). However, men age >70 years old experienced +0.37 more adverse events per patient compared with men age <60 years old (95% CI, 0.11-0.64; P = .006). CONCLUSIONS: PFS and OS were similar across age groups for the combination of docetaxel and ADT compared with ADT. Older men experienced a modest increase in adverse events per patient, highlighting the importance of balancing treatment benefits and adverse effects in this age group.

Cause of death during prostate cancer survivorship: A contemporary, US population-based analysis.

BACKGROUND: More than 3.6 million men in the United States harbor a diagnosis of prostate cancer (PCa). The authors sought to provide in-depth analyses of the causes of death for contemporary survivors. METHODS: The authors performed a population-based cohort study in the United States (2000-2016) to assess causes of death for men diagnosed with PCa stratified by demographics and tumor stage. Using general population data, they calculated standardized mortality ratios (SMRs) as observed-to-expected death ratios. RESULTS: In total, 752,092 men with PCa, including 200,302 who died (27%), were assessed. A total of 29,048 men with local/regional disease (17%) died of PCa, whereas more than 4-fold men died of other causes (n = 143,719 [83%]). SMRs for death from noncancer causes (0.77; 95% confidence interval [CI], 0.77-0.78) suggested that these men were less likely than the general population to die of most other causes. The most common noncancer cause of death was cardiac-related (23%; SMR, 0.76; 95% CI, 0.75-0.77). Among men with distant PCa, 90% of deaths occurred within 5 years of diagnosis. Although deaths due to PCa composed the majority of deaths (74%), SMRs suggested that men with distant PCa were at heightened risk for death from most other noncancer causes (1.50; 95% CI, 1.46-1.54) and, in particular, for cardiac-related death (SMR, 1.48; 95% CI, 1.41-1.54) and suicide (SMR, 2.32; 95% CI, 1.78-2.96). Further analyses demonstrated that causes of death varied by patient demographics. CONCLUSIONS: Causes of death during PCa survivorship vary by patient and tumor characteristics. These data provide valuable information regarding health care prioritization during PCa survivorship. LAY SUMMARY: Men with early-stage prostate cancer are 4-fold more likely to die of other causes, whereas those with advanced prostate cancer are at increased risk for several causes not related to prostate cancer in comparison with the general population. These findings can help guide physicians taking care of men with a diagnosis of prostate cancer.

Peyronie's disease: pharmacological treatments and limitations.

Introduction: Peyronie's disease (PD) is a disorder of the tunica albuginea from disordered and excessive deposition of collagen resulting in a palpable scar, pain, erect penile deformity and erectile dysfunction that significantly impacts patients both physically and emotionally.Areas Covered: Several treatment options have been described for PD, including shockwave therapy, traction therapy, both oral and intralesional pharmacological options, and surgery. This review seeks to examine the data for different types of non-surgical treatments for PD. We review how various treatment modalities impact several relevant clinical endpoints for Peyronie's disease, including effects on pain, penile curvature, plaque formation, and erectile function. We performed a literature search using PubMed and SCOPUS while referencing AUA, EAU, and CUA guidelines for management of Peyronie's Disease for studies published 1980-2020.Expert opinion: Intralesional collagenase injections have the strongest evidence and are the only FDA approved intralesional treatment for PD. Penile traction therapy (PTT) is low risk and may be beneficial in patients willing to invest significant time using the devices. Furthermore, oral combination therapy with other modalities may provide some benefit. Further investigation is required to better understand pathophysiology of PD and clarify the therapeutic utility of existing treatments, potentially with a multimodal strategy.

Survival following upfront chemotherapy for treatment-naïve metastatic prostate cancer: a real-world retrospective cohort study.

BACKGROUND: Upfront chemotherapy prolongs overall survival for men with metastatic, hormone-sensitive prostate cancer (mHSPC) based on data from clinical trials. We sought to assess the association between upfront chemotherapy and overall survival in men with mHSPC in a real-world cohort. METHODS: We performed a retrospective cohort study of men with de novo, treatment-naïve metastatic prostate cancer from a large, national cancer database in the United States (2014-2015). Men in the upfront chemotherapy group received chemotherapy within 4 months of diagnosis (n = 1033, 28%) versus no chemotherapy or chemotherapy later than 12 months after diagnosis (controls; n = 2704, 72%). Overall survival was assessed using Kaplan-Meier estimates and compared using multivariable Cox regression analysis. RESULTS: After a median follow-up of 23 months, median overall survival was 35.7 months in the upfront chemotherapy group and 32.5 months for controls (log-rank p < 0.001). After adjusting for patient and clinical variables, upfront chemotherapy was associated with longer overall survival (hazard ratio 0.78, 95% confidence interval 0.68-0.89, p < 0.001). In exploratory analyses, the association between upfront chemotherapy and overall survival did not differ by age groups, race, or number of comorbidities (all interaction p > 0.2). CONCLUSIONS: In this real-world cohort, upfront chemotherapy for mHSPC was associated with longer overall survival. These data support the continued use of chemotherapy for men with mHSPC regardless of race or age if they are fit for chemotherapy and underscore the importance of evaluating cancer therapeutics outside of clinical trials to demonstrate treatment efficacy in populations that may be underrepresented in clinical trials.

Inflammatory Bowel Disease and the Risk of Prostate Cancer.

BACKGROUND: There are limited data examining the risk of prostate cancer (PCa) in patients with inflammatory bowel disease (IBD). OBJECTIVE: To compare the incidence of PCa between men with and those without IBD. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, matched-cohort study involving a single academic medical center and conducted from 1996 to 2017. Male patients with IBD (cases=1033) were randomly matched 1:9 by age and race to men without IBD (controls=9306). All patients had undergone at least one prostate-specific antigen (PSA) screening test. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier and multivariable Cox proportional hazard models, stratified by age and race, evaluated the relationship between IBD and the incidence of any PCa and clinically significant PCa (Gleason grade group ≥2). A mixed-effect regression model assessed the association of IBD with PSA level. RESULTS AND LIMITATIONS: PCa incidence at 10yr was 4.4% among men with IBD and 0.65% among controls (hazard ratio [HR] 4.84 [3.34-7.02] [3.19-6.69], p<0.001). Clinically significant PCa incidence at 10yr was 2.4% for men with IBD and 0.42% for controls (HR 4.04 [2.52-6.48], p<0.001). After approximately age 60, PSA values were higher among patients with IBD (fixed-effect interaction of age and patient group: p=0.004). Results are limited by the retrospective nature of the analysis and lack of external validity. CONCLUSIONS: Men with IBD had higher rates of clinically significant PCa when compared with age- and race-matched controls. PATIENT SUMMARY: This study of over 10000 men treated at a large medical center suggests that men with inflammatory bowel disease may be at a higher risk of prostate cancer than the general population.