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BACKGROUND Small cell neuroendocrine (NE) carcinomas of the prostate classically lose androgen receptor (AR) expression, may harbor loss of the RB1, TP53, and PTEN tumor suppressor genes, and are associated with a poor prognosis. However usual-type adenocarcinomas may also contain areas of NE differentiation, and in this context the molecular features and biological significance are less certain. METHODS We examined the molecular phenotype and oncologic outcomes of primary prostate adenocarcinomas with ≥5% NE differentiation (≥5% chromogranin A-positive NE cells in any given tumor spot on tissue microarray) using three independent study sets: a set of tumors with paneth cell-like NE differentiation (n = 26), a retrospective case-cohort of intermediate- and high-risk patients enriched for adverse outcomes (n = 267), and primary tumors from a retrospective series of men with eventual castration-resistant metastatic prostate cancer (CRPC) treated with abiraterone or enzalutamide (n = 55). RESULTS Benign NE cells expressed significantly lower quantified AR levels compared with paired benign luminal cells (P

BACKGROUND Guidelines have changed recently to include genetic counseling (GC) and/or genetic testing (GT) for all men with aggressive prostate cancer (PCa). This study aimed to identify what information men with PCa desire before and from GC. METHODS Focus groups were conducted with men who have PCa. Audio recordings were analyzed for themes related to GT, the information they desired from health care providers, and implications for family members. RESULTS Thirty-seven men with PCa participated in seven focus groups. Nearly all men felt GT was beneficial and impactful for their family and themselves. Most men were unaware of the risks to female relatives associated with hereditary cancer. Participants discussed that genetics should be incorporated at an appropriate time of their diagnostic journey. CONCLUSION This study showed that men valued GC and GT for personal and familial implications, and often did not associate PCa genetics with risk for female relatives to develop cancer. Consideration should be given to the GC timing in regard to where men are in their treatment process. Providers referring patients can leverage patient motivations and utilize their relationship with the patient to determine the appropriate timing and personalize discussion with the patient regarding GC and GT.

Background Statins compete with DHEAS for influx through the SLCO2B1 transporter, which may prolong time to progression (TTP) on androgen deprivation therapy. Abiraterone acetate (AA) may also undergo SLCO-mediated transport. Based on preclinical findings showing antagonism, we hypothesized that statins may compete with AA for influx via SLCO2B1 and could negatively impact drug efficacy. Methods We queried two institutional clinical databases (Dana-Farber Cancer Institute [DFCI], Johns Hopkins University [JHU]) for CRPC patients treated with AA. Treatment duration was a surrogate for TTP. Associations between statin use and AA duration were estimated using the Kaplan-Meier method. Multivariable Cox regression modeling adjusted for known prognostic factors. Results Of the 224 DFCI and 270 JHU patients included, the majority (96%) had metastatic disease. Nearly half (41% and 45%) were statin users. In the DFCI cohort, there was a trend toward longer AA duration in statin users: 14.2 versus 9.2 months (HR 0.79, 95%CI: 0.57-1.09, P = 0.14). There was no association between statin use and AA duration in the JHU cohort: 8.3 versus 8.0 months (HR 0.89, 95%CI: 0.69-1.16, P = 0.38) in the statin users versus non-users, except for a trend in patients that had not previously received docetaxel or enzalutamide (HR 0.79; 95%CI: 0.57-1.10). Conclusions Contrary to our initial hypothesis, there was a trend toward longer (rather than shorter) AA duration in statin users in the entire DFCI cohort and in the enzalutamide- and docetaxel-naive JHU patients. Together, these results do not support the hypothesis that statins interfere with AA efficacy.

BACKGROUND There are no validated clinical decision tools to aid optimal treatment selection in men with metastatic castration-resistant prostate cancer (mCRPC). Frequently, abiraterone and enzalutamide are used prior to chemotherapy in mCRPC, given the more favorable safety profiles. However, there is no published data on clinical outcomes regarding best sequencing of these two agents. METHODS A retrospective analysis of consecutive mCRPC patients treated with enzalutamide and abiraterone at Johns Hopkins was conducted. Patients were treated with sequential enzalutamide and abiraterone, in either order. The combined progression-free survival (PFS: PFS1 + PFS2) of abiraterone-to-enzalutamide was compared to the reverse sequence, where PFS1 and PFS2 represented clinical/radiographic progression-free survival on the first and second agents, respectively. Overall survival (OS) from the start of the first therapy to death and PSA response rates (defined as ≥50% PSA declines at any time) were also compared between groups. Outcomes were adjusted using propensity score-weighted multivariable Cox analyses. RESULTS Eighty-one patients who satisfied our entry criteria were identified: 65 in the abiraterone-to-enzalutamide group and 16 in the enzalutamide-to-abiraterone group. There were no significant baseline differences between groups. Multivariable analysis suggested a difference between groups favoring the abiraterone-to-enzalutamide sequence with respect to combined PFS (HR 0.37, 95%CI 0.22–0.64, P

BACKGROUND Recent advances have yielded multiple new life-prolonging treatments for men with metastatic castration-resistant prostate cancer (mCRPC) including chemotherapy, next-generation hormonal therapy, immunotherapy, and radiopharmaceutical products. However, the optimal sequencing of these agents to maximize clinical benefit remains unclear. Recent data from the CHAARTED and STAMPEDE studies suggest that early use of docetaxel in men with metastatic hormone-sensitive prostate cancer (mHSPC) significantly improves survival, but whether early compared with delayed use of chemotherapy also provides a survival advantage in mCRPC is unknown. METHODS A retrospective analysis of consecutive mCRPC patients treated at Johns Hopkins is reported. Patients included were treated with sequential docetaxel and abiraterone, in either order. The combined progression-free survival (combined PFS: PFS1 + PFS2) of abiraterone-to-docetaxel is compared to the reverse sequence, where PFS1 and PFS2 represent progression-free survival on the first and second agents respectively. Overall survival (OS) from the start of the first therapy to death is compared between groups. Baseline characteristics are reported prior to the start of the first agent in the sequence. Propensity score-weighted multivariable models and Kaplan—Meier analysis are used for evaluation of the primary and secondary outcomes. RESULTS Fifty-eight patients who began treatment for mCRPC between January 2011 (the year of abiraterone's FDA-approval) and February 2015 were identified: 26 were in the docetaxel-to-abiraterone group and 32 were in the abiraterone-to-docetaxel group. Patients in the abiraterone-to-docetaxel group had more Gleason 8–10 tumors, greater metastatic burden in bone, and higher median PSAs than those in the docetaxel-to-abiraterone group. Propensity score-weighted univariate analyses for combined PFS (HR 0.82; 95%CI 0.50–1.33; P = 0.41) and OS (HR 0.79; 95%CI 0.50–1.25; P = 0.31) do not identify any significant differences based on treatment sequence. Propensity score-weighted multivariate analyses for combined PFS (HR 0.91; 95%CI 0.52–1.60; P = 0.74) and OS (HR 0.98; 95%CI 0.59–1.63; P = 0.95) also do not identify any significant differences between groups. CONCLUSIONS We do not observe differences in clinical outcomes based on alternative sequencing of abiraterone and docetaxel in men with mCRPC. Treatment sequencing should be determined by patient and disease characteristics, comorbidities and end-organ function, ability to tolerate side effects, and patient preferences. Studies evaluating biomarkers to inform optimal treatment sequencing in men with mCRPC are urgently needed. Prostate 75:1814–1820, 2015. © 2015 Wiley Periodicals, Inc.

There are no validated clinical decision tools to aid optimal treatment selection in men with metastatic castration-resistant prostate cancer (mCRPC). Frequently, abiraterone and enzalutamide are used prior to chemotherapy in mCRPC, given the more favorable safety profiles. However, there is no published data on clinical outcomes regarding best sequencing of these two agents.A retrospective analysis of consecutive mCRPC patients treated with enzalutamide and abiraterone at Johns Hopkins was conducted. Patients were treated with sequential enzalutamide and abiraterone, in either order. The combined progression-free survival (PFS: PFS1 + PFS2) of abiraterone-to-enzalutamide was compared to the reverse sequence, where PFS1 and PFS2 represented clinical/radiographic progression-free survival on the first and second agents, respectively. Overall survival (OS) from the start of the first therapy to death and PSA response rates (defined as ≥50% PSA declines at any time) were also compared between groups. Outcomes were adjusted using propensity score-weighted multivariable Cox analyses.Eighty-one patients who satisfied our entry criteria were identified: 65 in the abiraterone-to-enzalutamide group and 16 in the enzalutamide-to-abiraterone group. There were no significant baseline differences between groups. Multivariable analysis suggested a difference between groups favoring the abiraterone-to-enzalutamide sequence with respect to combined PFS (HR 0.37, 95%CI 0.22-0.64, P 0.001). There was no statistical difference in OS between the groups after multivariable adjustment (HR 0.57, 95%CI 0.29-1.11, P = 0.098), although OS was numerically superior in the abiraterone-to-enzalutamide group.We observed differences suggesting improved outcomes favoring the abiraterone-to-enzalutamide sequence in men with mCRPC, with statistical confirmation in terms of PFS but not OS. Prospective studies are required to verify these hypothesis-generating findings. Further evaluation of biomarkers to inform optimal treatment sequencing in men with mCRPC is urgently needed. Prostate 77:33-40, 2017. © 2016 Wiley Periodicals, Inc.

Recent advances have yielded multiple new life-prolonging treatments for men with metastatic castration-resistant prostate cancer (mCRPC) including chemotherapy, next-generation hormonal therapy, immunotherapy, and radiopharmaceutical products. However, the optimal sequencing of these agents to maximize clinical benefit remains unclear. Recent data from the CHAARTED and STAMPEDE studies suggest that early use of docetaxel in men with metastatic hormone-sensitive prostate cancer (mHSPC) significantly improves survival, but whether early compared with delayed use of chemotherapy also provides a survival advantage in mCRPC is unknown.A retrospective analysis of consecutive mCRPC patients treated at Johns Hopkins is reported. Patients included were treated with sequential docetaxel and abiraterone, in either order. The combined progression-free survival (combined PFS: PFS1 + PFS2) of abiraterone-to-docetaxel is compared to the reverse sequence, where PFS1 and PFS2 represent progression-free survival on the first and second agents respectively. Overall survival (OS) from the start of the first therapy to death is compared between groups. Baseline characteristics are reported prior to the start of the first agent in the sequence. Propensity score-weighted multivariable models and Kaplan-Meier analysis are used for evaluation of the primary and secondary outcomes.Fifty-eight patients who began treatment for mCRPC between January 2011 (the year of abiraterone's FDA-approval) and February 2015 were identified: 26 were in the docetaxel-to-abiraterone group and 32 were in the abiraterone-to-docetaxel group. Patients in the abiraterone-to-docetaxel group had more Gleason 8-10 tumors, greater metastatic burden in bone, and higher median PSAs than those in the docetaxel-to-abiraterone group. Propensity score-weighted univariate analyses for combined PFS (HR 0.82; 95%CI 0.50-1.33; P = 0.41) and OS (HR 0.79; 95%CI 0.50-1.25; P = 0.31) do not identify any significant differences based on treatment sequence. Propensity score-weighted multivariate analyses for combined PFS (HR 0.91; 95%CI 0.52-1.60; P = 0.74) and OS (HR 0.98; 95%CI 0.59-1.63; P = 0.95) also do not identify any significant differences between groups.We do not observe differences in clinical outcomes based on alternative sequencing of abiraterone and docetaxel in men with mCRPC. Treatment sequencing should be determined by patient and disease characteristics, comorbidities and end-organ function, ability to tolerate side effects, and patient preferences. Studies evaluating biomarkers to inform optimal treatment sequencing in men with mCRPC are urgently needed.