BACKGROUND: Multiparametric MRI (mpMRI) parameters of pT3a prostate cancer have not been examined in large cohort studies. Therefore, we aimed to identify factors associated with up-staging of mpMRI cT3a in post-operative histopathological confirmation.
METHODS: Retrospective analysis of a prospectively maintained database of a single UK cancer centre. Only cT3a cases who underwent robotic-assisted radical prostatectomy (RARP) were included (N = 383). MRI and specimen histopathology was reviewed independently by expert uro-radiologists and uro-histopathologists, respectively. Factors included age, BMI, prostate-specific antigen (PSA) level, biopsy international society of urological pathology (ISUP) grade, Prostate Imaging Reporting & Data System (PI-RADS®) score, tumour size, tumour coverage of gland (%), gland weight and surgical margins were analysed as predictors of pT3a prostate cancer.
RESULTS: N = 383. Mean age 66 years (58-71), mean BMI 27.1 kg/m2 (25.0-30.0). 314 (82.0%) cases down- unchanged or down-staged, and 69 (18.0%) cases upstaged. PSA level (P = 0.002), PI-RADS score (P < 0.001) and ISUP grade (P < 0.001) are positively associated with upstage categories. ISUP grade ≥3 (OR 5.45, CI 1.88, 9.29, P < 0.002), PI-RADS score ≥4 (OR 3.92, CI 1.88-9.29, P < 0.001) and tumour coverage (OR 1.06, CI 1.05-1.08, P < 0.001) significantly positively associated with upstaging disease, with concurrent decreased probability of downstaging (OR 0.55, 0.14, 0.44, respectively, P < 0.05). Tumour coverage was positively correlated with increasing positive surgical margins (P < 0.05). Capsular contact > 15 mm was very unlikely to be upstaged (OR 0.36, CI 0.21-0.62, P < 0.001), aligning with published results past the widely accepted significant level for extracapsular disease on MRI.
CONCLUSIONS: The study has identified PSA level, ISUP, PI-RADS score, tumour volume and percentage coverage are key predictive factors in cT3a upstaging. This study uniquely shows tumour coverage percentage as a predictor of cT3a upstaging on mpMRI. ISUP is the strongest predictor, followed by PI-RADS score and tumour coverage of gland. Multi-institutional studies are needed to confirm our findings.

OBJECTIVE: To assess efficacy and safety of prostatic artery embolization (PAE) in patients with advanced prostate cancer (PCa).
METHODS: In this prospective single-center, single-arm, pilot study, 9 men with advanced PCa underwent PAE. PAE was performed with the use of 250-400 µm Embozene microspheres (Boston Scientific, Natick, Massachusetts, USA). International Prostate Symptoms Score (IPSS), urinary peak flow (Qmax) and post-void residual urine volume (PVR) was assessed at 12 weeks and up to 12 months. Changes in total prostate volume (TPV) and tumor responses by PSA, changes in tumor volume and evaluation of tumor regression by multiparametric magnetic resonance imaging were assessed at 12 weeks after PAE.
RESULTS: IPSS reduction in median 6 points (0-19) and a significant decrease in PVR from median 70 (20-600) mL to 10 (0-280) mL could be achieved within 12 weeks after PAE. Median TPV and tumor volumes (TV) increased slightly from 19.7 (6.4-110.8) mL to 23.4 (2.4-66.3) mL and 6.4 (4.6-18.3) mL to 8.1 (2.4-25.6) mL at a median of 12 weeks after the procedure. Significant tumor necrosis (≥ 50%) was found in one patient. Eight patients showed > 50% of viable tumor on post-PAE MRI according to MRI. Only one Clavien-Dindo Grade 1 adverse event related to PAE occurred.
CONCLUSIONS: PAE with the use of 250-400 µm microspheres is feasible, safe and effective in some patients with advanced PCa regarding functional outcomes. A cytoreductive effect might be achieved in individual patients but must be further assessed.
BACKGROUND: NCT03457805.

BACKGROUND: Social well-being impacts cancer patients\' health-related quality of life (HRQOL) and coping style. This secondary analysis was conducted to examine whether advanced prostate cancer survivors who had experienced low social well-being would benefit from a web-based cognitive behavioral stress management (CBSM) intervention.
METHODS: APC survivors (N = 192) who had received androgen deprivation therapy (ADT) were randomized to a 10-week CBSM or a health promotion (HP) control condition. A subsample of participants (n = 61) with low pre-intervention SWB (measured by social support from and relationship satisfaction with family and friends) was included in the study. Multilevel models compared participants\' PC-specific quality of life (sexual, hormonal, urinary), affect-based psychosocial burden (cancer-related anxiety and distress), and coping strategies at baseline, 6 months, and 12 months. Covariates were included in all models as appropriate.
RESULTS: Participants randomized to the CBSM condition showed significantly greater improvements in fear of cancer recurrence and cancer-related intrusive thoughts than those in the HP control condition. A significant condition by time interaction was also found, indicating that CBSM improved participants\' PC-related fear in both short- (6 months) and long-term (12 months). However, the CBSM intervention did not significantly impact APC-related symptom burden. Only for the urinary domain, clinically meaningful changes (CBSM vs HP) were observed. In addition, all participants, regardless of condition, reported less coping (e.g., emotion-, problem- and avoidance-focused) over time.
CONCLUSIONS: As predicted, the CBSM intervention improved several affect-based psychosocial outcomes for APC survivors with low baseline SWB.

BACKGROUND: In the HERO study, relugolix demonstrated sustained testosterone suppression superior to that of leuprolide acetate (97% vs 89%; difference 7.9% [95% confidence interval, 4.1-12%; p < 0.001]).
OBJECTIVE: To analyze testosterone recovery in a prespecified subset of men from the HERO study not indicated to continue androgen deprivation therapy.
METHODS: Men (N = 934) were randomized (2:1) to receive relugolix 120 mg orally daily or leuprolide acetate injections every 12 wk for 48 wk.
METHODS: Testosterone recovery was assessed in 184 men who completed 48 wk of treatment. During the 90-d recovery period, assessments included time to testosterone recovery (>280 ng/dl; ≥80% of baseline testosterone), serum levels of prostate-specific antigen and pituitary hormones, and adverse events.
CONCLUSIONS: The cumulative incidence rate of testosterone recovery to >280 ng/dl at 90 d following drug discontinuation was significantly higher in the relugolix cohort (n = 137) than in the leuprolide acetate cohort (n = 47; 54% vs 3.2%; nominal p = 0.002). The median time to testosterone recovery was faster following relugolix treatment than with leuprolide acetate treatment (86.0 d vs 112.0 d). Compared with leuprolide acetate, more men treated with relugolix achieved ≥80% of baseline testosterone levels (39% vs 2.1%). Men ≤65 yr and those with baseline testosterone greater than the median had a higher incident rate of testosterone recovery. Adverse events were generally similar between treatment groups. One limitation is the short testosterone recovery follow-up period.
CONCLUSIONS: Oral relugolix had faster and more complete recovery of testosterone to normal levels after treatment discontinuation than leuprolide acetate in a subset of men from the HERO study. The clinical implications of a faster testosterone recovery with relugolix may be significant for men being treated with androgen deprivation therapy and influence treatment decisions.
RESULTS: The male hormone testosterone is reduced during androgen deprivation therapy for prostate cancer. Reduced testosterone levels cause side effects, impacting patient quality of life. When treatment is stopped, the side effects lessen over time as the levels of testosterone come back to pretreatment range (testosterone recovery). In this study, we found that the time to testosterone recovery was faster with relugolix than with leuprolide acetate.

UNASSIGNED: This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time.
UNASSIGNED: In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes.
UNASSIGNED: These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.

The potential involvement of a sexually transmitted agent has been suggested to contribute to the high number of prostate cancers in the United States and worldwide. We investigated the relationship of Trichomonas vaginalis seropositivity with prostate cancer risk in a nested case-control study within the Multiethnic Cohort in Hawaii and California using blood samples collected prior to cancer diagnoses. Incident cases of advanced prostate cancer (intermediate- to high-grade based on Gleason score ≥ 7 and/or disease spread outside the prostate) were matched to controls by age, ethnicity, and the date of blood collection. T. vaginalis serostatus was measured using an ELISA detecting IgG antibodies against a recombinant T. vaginalis α-actinin protein. Seropositivity to T. vaginalis was observed in 35 of 470 (7.4%) cases and 26 of 470 (5.5%) controls (unadjusted OR = 1.47, 95% CI 0.82-2.64; adjusted OR = 1.31, 95% CI 0.67-2.53). The association was similarly not significant when cases were confined to extraprostatic tumors having regional or distant spread (n = 121) regardless of grade (unadjusted OR = 1.37, 95% CI 0.63-3.01; adjusted OR = 1.20, 95% CI 0.46-3.11). The association of T. vaginalis with prostate cancer risk did not vary by aspirin use. Our findings do not support a role for T. vaginalis in the etiology of advanced prostate cancer.

Background: Relugolix is an oral GnRH receptor antagonist approved for men with advanced prostate cancer. Relugolix treatment has demonstrated an ability to lower testosterone to sustained castration levels in the phase 4 HERO study. Herein, we describe the results of a secondary endpoint of castration resistance-free survival (CRFS) during 48 weeks of treatment and profile patients with castration-resistant prostate cancer (CRPC). Methods: Subjects were 2:1 randomized to either relugolix 120 mg orally once daily (after a single 360 mg loading dose) or 3-monthly injections of leuprolide for 48 weeks. CRFS, defined as the time from the date of first dose to the date of confirmed prostate-specific antigen progression while castrated or death due to any reason was conducted in the metastatic disease population and the overall modified intention-to-treat (mITT) populations. Results: The CRFS analysis (mITT population) included 1074 men (relugolix: n = 717; leuprolide: n = 357) with advanced prostate cancer as well as 434 men (relugolix: n = 290; leuprolide: n = 144) with metastatic prostate cancer. In the metastatic disease populations, CRFS rates were 74.3% (95% CI: 68.6%, 79.2%) and 75.3% (95% CI: 66.7%, 81.9%) in the relugolix and leuprolide groups, respectively (hazard ratio: 1.03 [0.68, 1.57]; p = 0.84) at week 48. Results in the overall mITT population were similar to the metastatic population. No new safety findings were identified. Conclusions: In men with metastatic disease or in the overall population of the HERO study, CRFS assessed during the 48-week treatment with relugolix was not significantly different than standard-of-care leuprolide. Relugolix had similar efficacy for men with/without CRFS progression events.

BACKGROUND: Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, demonstrated testosterone suppression to castrate levels in men with advanced prostate cancer (PCa) in the HERO study. Since advanced PCa and its treatments can impact patients\' daily life, it is imperative to understand the impact of systemic therapy on patient health-related quality of life (HRQOL).
OBJECTIVE: To report the HRQOL for patients on relugolix compared with those on leuprolide in on-treatment and testosterone recovery periods of the HERO study.
METHODS: A phase 3 randomized controlled study was conducted in 934 patients with advanced PCa.
METHODS: Patients underwent 2:1 randomization and received relugolix 120 mg orally once daily or leuprolide 3-mo injections for 48 wk. Testosterone recovery was evaluated in a patient subset.
METHODS: HRQOL evaluations were based on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) and the Prostate Cancer Module (EORTC QLQ-PR25) during treatment and testosterone recovery phases. In a post hoc analysis, predictors of HRQOL deterioration were evaluated.
CONCLUSIONS: No statistically significant differences between the two groups were found in changes from baseline to the end of treatment in either the EORTC QLQ-C30 or the EORTC QLQ-PR25 instrument. During the testosterone recovery phase, hormonal treatment-related symptoms scores were lower for relugolix than for leuprolide, suggesting a lower burden of hormone-related symptoms associated with a treatment that has more rapid testosterone recovery after treatment cessation. Limitations include low patient numbers in the testosterone recovery group.
CONCLUSIONS: Oral relugolix is a therapeutic option with similar patient-reported HRQOL to leuprolide, providing an oral option for androgen deprivation therapy associated with a more rapid testosterone reduction.
RESULTS: In men with advanced prostate cancer, relugolix had similar health-related quality of life to leuprolide.

UNASSIGNED: Studies have highlighted how advanced prostate cancer causes biographical disruption and presents challenges to masculine identities for men. This article draws on a wider study that focused on the experiences of men living with advanced prostate cancer and their caregivers. Although men\'s experience of advanced illness is not overlooked in the literature, only a small body of work has taken an in-depth look at men\'s experiences with advanced prostate cancer and their caregivers in a non-Westernised cultural and social context.
UNASSIGNED: To explore how advanced prostate cancer impacts on men\'s masculine identity from the perspective of patients and their caregivers.
UNASSIGNED: A qualitative study of men living with advanced prostate cancer (n = 23) and family caregivers (n = 23) in Ghana. We used the Consolidated Criteria for Reporting Qualitative Studies (COREQ) as the reporting guideline.
UNASSIGNED: The findings from this study highlight profound challenges for most men to their masculine identities, from both the treatment and the symptoms of advanced prostate cancer within a non-Westernised, patriarchal society. Four main themes were developed. These were the impact on masculinity in terms of: (1) physical changes, (2) sexual ability, (3) socio-economic roles and (4) expressing emotions. Changes in physical appearance, feeling belittled, having no active sexual life and the inability to continue acting as provider and protector of the family made some men describe their situation as one of moving out of the \'frying pan into the fire\'.
UNASSIGNED: This study revealed the impact of advanced prostate cancer on masculine identity. These narratives add a new dimension to what is already known about the impacts on men\'s masculine identities when dealing with advanced prostate cancer. This knowledge can help improve the care provided to men with advanced prostate cancer with emphasis on the cultures, beliefs and aspirations of these men and their caregivers.

Androgen-deprivation therapy (ADT) has been widely used for the treatment of advanced prostate cancer. However, prognosis and adverse events (AEs) vary among patients. This study aimed to identify genetic markers able to predict the outcome of ADT. Japanese patients treated with primary ADT for advanced prostate cancer in the KYUCOG-1401 trial were enrolled as a development set. A distinct population of advanced prostate cancer cases treated with ADT was included as a validation set. Single-nucleotide polymorphisms (SNPs) associated with radiographic progression-free survival (rPFS) at 1 year and AEs including de novo diabetes mellitus (DM), arthralgia, and de novo dyslipidemia were identified in the development set by a genome-wide association study (GWAS). The SNPs associated with rPFS in the development study were then genotyped in the validation set. GWAS followed by validation identified SNPs (rs76237622 in PRR27 and rs117573572 in MTAP) that were associated with overall survival (OS) in ADT. A genetic prognostic model using these SNPs showed excellent predictive efficacy for PFS and OS in ADT. In addition, GWAS showed that several SNPs were associated with de novo DM, arthralgia, and de novo dyslipidemia in ADT. This study identified novel multiple SNPs that correlated with outcomes in ADT. Future studies on correlations affecting the therapeutic efficacy of ADT-based combination therapies would make a valuable contribution to the development of personalized medicine.