Receiving Androgen Deprivation Therapy Research Articles

Elective Pelvic Lymph Node Radiation Therapy and the Risk of Death in Patients With Unfavorable-Risk Prostate Cancer: A Postrandomization Analysis.

Although a contemporary randomized clinical trial has led to the use of whole-pelvic radiation therapy (WPRT), long-term data evaluating a potential reduction in mortality are lacking and are addressed in the current study. From 2005 to 2015, 350 men with localized, unfavorable-risk prostate cancer (PC) were randomly assigned to receive androgen deprivation therapy (ADT) and RT plus docetaxel versus ADT and RT. Treatment of the pelvic lymph nodes was at the discretion of the treating physician. Multivariable Cox and Fine and Grays regression analyses were performed to assess whether a significant association existed between radiation treatment volume and all-cause mortality (ACM) and PC-specific mortality (PCSM), respectively, adjusting for known PC prognostic factors and comorbidity. An interaction term between age (categorized by dichotomization at 65 years to enable clinical interpretation and applicability of the results and which approximates the median (66 years [IQR, 61-70]) and radiation treatment volume was included in the analysis. After a median follow-up of 10.20 years (IQR, 7.96-11.41), 89 men died (25.43%); of these, 42 died of PC (47.19%). Of the 350 randomly assigned patients, 88 (25.14%) received WPRT. In men younger than 65 years, WPRT was associated with a significantly lower ACM risk (adjusted hazard ratio [AHR], 0.33 [95% CI, 0.11 to 0.97]; P = .04) and lower PCSM risk (AHR, 0.17 [95% CI, 0.02 to 1.35]; P = .09) after adjusting for covariates, whereas this was not the case for men 65 years or older. WPRT has the potential to reduce mortality in younger men with unfavorable-risk PC.

Variation in management of lymph node positive prostate cancer after radical prostatectomy within a statewide quality improvement consortium

BackgroundPatients with lymph node positive (pN+) disease found at the time of radical prostatectomy with pelvic lymphadenectomy for clinically localized prostate cancer (CaP) are at high risk of disease persistence and progression. Contemporary management trends of pN+ CaP are not well described. Materials and methodsPatients in the Michigan Urologic Surgery Improvement Collaborative (MUSIC) with clinically localized prostate cancer who underwent radical prostatectomy between 2012 and 2023 with cN0/pN+ disease were identified. The primary outcome was to evaluate patient and practice-level factors associated with time to secondary post-RP treatment. Secondary outcomes included practice-level variation in management of pN+ CaP and rates of secondary treatment modality. To assess factors associated with secondary treatment, a Cox proportional hazards model of a 60-day landmark analysis was performed. ResultsWe identified 666 patients with pN+ disease. Overall, 66% underwent secondary treatment within 12 months post-RP. About 19% of patients with detectable post-RP PSA did not receive treatment. Of patients receiving secondary treatment after 60-days post-RP, 34% received androgen deprivation therapy (ADT) alone, 27% received radiation (RT) alone, 36% received combination, and 4% received other systemic therapies. In the multivariable model, pathologic grade group (GG)3 (HR 1.5; 95%CI: 1.05–2.14), GG4-5 (HR 1.65; 95%CI: 1.16–2.34), positive margins (HR 1.46; 95%CI: 1.13–1.88), and detectable postoperative PSA ≥0.1 ng/ml (HR 3.46; 95%CI: 2.61–4.59) were significantly associated with secondary post-RP treatment. There was wide variation in adjusted practice-level 12-month secondary treatment utilization (28%–79%). ConclusionsThe majority pN+ patients receive treatment within 12 months post-RP which was associated with high-risk pathological features and post-RP PSA. Variation in management of pN+ disease highlights the uncertainty regarding the optimal management. Understanding which patients will benefit from secondary treatment, and which type, will be critical to minimize variation in care.

Estimating cost of prostate cancer management: an experience from Tanzania

BackgroundProstate cancer (PC) is a significant public health problem affecting men worldwide and ranks third in incidence and mortality in East Africa. Cost of prostate cancer management is high in low-income countries because majority of patients presents with advanced (metastatic) PC. The cost related to management of PC including castrate resistant cancer in Tanzania has remained unknown; hence, policy makers do not have enough information for planning and resource allocation. This study therefore aimed to document costs related to the management of patients with prostate cancer including castrate resistant prostate cancer (CRPC) at Muhimbili National Hospital in Tanzania.MethodsThis was a retrospective descriptive hospital-based study which was conducted at Muhimbili National Hospital (MNH). Case notes of patients who were treated for prostate cancer were retrieved from medical records for review. A structured checklist was used to extract information regarding age, clinical presentation, investigations, stage of disease, type of treatment, payment modality and reimbursement. We considered data on the direct costs of prostate cancer management (diagnosis, treatment and follow-up) based on hospital price list of different categories. Costs reported were based on payment category in total and unit cost but also source of funding. Descriptive statistics were prepared and summarized as tables and figures.ResultsA total of 292 case notes of patients with prostate cancer were reviewed of which 189 patients received androgen deprivation therapy. Ninety-six (50.8%) met the criteria for the diagnoses of CRPC, and their mean age was 71.23 ± 4.2. Most of the patients had a poorly differentiated histology with prostate-specific antigen (PSA) over 100 ng/l. Bilateral orchiectomy was the most common treatment modality offered for advanced prostate cancer. Total cost for all PC patients was $148,136.4, equivalent to a unit cost per patient of $507.3. However, patients were in different categories of payment, 53% were public patients with an average cost of $471.3 per patient; 36.6% were cost sharing patients with an average cost of $441.8 per patient; 8.2% were National Health Insurance (NHIF) patients with an average cost of $893.8 per patient; and only 2.2% were private patients with an average cost of $1060.9 per patient.ConclusionCosts related to prostate cancer management need harmonization to accommodate different categories of patients in need.

A phase I trial of enzalutamide plus selective glucocorticoid receptor modulator relacorilant in patients with metastatic castration resistant prostate cancer.

Majority of patients with metastatic prostate cancer who receive androgen deprivation therapy and androgen receptor (AR) signaling inhibitors progress. Activation of the glucocorticoid receptor (GR) is associated with ARSI-resistance. This single-arm phase I trial assessed safety and pharmacokinetic feasibility of combined AR antagonist (enzalutamide) and selective GR modulator (relacorilant) in metastatic castration-resistant prostate cancer (mCRPC) patients. This was a phase I trial (NCT03674814) of relacorilant and enzalutamide in refractory mCRPC patients enrolled using 6+3 design. Enzalutamide dose was kept constant at 120 mg/day with escalating doses of relacorilant based on safety and pharmacokinetic measures in cohorts of ≥ 6 patients. Primary objective was safety and establishment of pharmacologically active doses. Secondary objectives were related to antitumor activity. Thirty-five mCRPC patients were enrolled. Twenty-three were accrued across 3 dose cohorts in the dose escalation phase and twelve enrolled at the recommended phase 2 dose. The combination was generally well-tolerated and safe and achieved desirable enzalutamide pharmacokinetics. RP2D of 120 mg/day + 150 mg/day respectively was established. Median time on study was 2.2 months with 4 patients remaining on study for longer than 11 months. Four of twelve evaluable patients had a PSA partial response. This is the first prospective trial combining an AR antagonist and a non-steroidal selective GR modulator. The combination was safe and well tolerated with PSA response and prolonged disease control observed in a limited subset of patients. Further prospective trials are justified to evaluate efficacy and identify predictive biomarkers of response.

Evaluating appropriateness of 18F-fluciclovine PET/CT relative to standard of care imaging guidelines and the impact of ADT on positivity: a prospective study in 62 Veterans Administration patients at a single institution.

According to the National Comprehensive Cancer Network Guidelines, 18F-fluciclovine PET/CT is considered appropriate after negative standard of care (SOC) imaging. To prospectively compare 18F-fluciclovine to SOC imaging, investigate whether it should be done when SOC imaging is (+), and evaluate its detection rate in patients receiving androgen deprivation therapy. We recruited 57 prostate cancer patients with biochemical recurrence with 18F-fluciclovine PET/CT and SOC imaging within 30 days. Prostate-specific antigen (PSA) level, Gleason score (GS), history of radical prostatectomy (RP), radiation therapy (RT) or hormone therapy (HT) were reviewed. The 57 patients had a median PSA of 2.6 and average GS of 7.4; 27 (47.4%) had RP, 28 (49.1%) had RT, 1 (1.75%) had HT and 1 (1.75%) observation only. 18F-fluciclovine identified disease recurrence in 45/57 patients (78.9%), including oligometastasis in 18/45 (40%). SOC imaging identified recurrent disease in 12/57 patients (21.1%) while 18F-fluciclvoine identified additional sites of disease in 11/12 (91.7%). The (+) 18F-fluciclovine studies had a median PSA 2.6 ng/ml compared to 6.0 ng/ml in the (+) SOC studies. 18F-fluciclovine was superior to SOC imaging for lesion detection, identification of oligometastasis and identification of additional sites of disease.

Secondary analysis of late major gastrointestinal and genitourinary toxicities in unfavorable-risk prostate cancer patients receiving docetaxel: Insights from a randomized trial.

This study sought to evaluate the late toxicity associated with neoadjuvant and concurrent docetaxel and radiation therapy in patients with prostate cancer. A secondary analysis was performed of the phase 3 multicenter randomized trial (Dana-Farber Cancer Institute 05-043) including 350 patients with nonmetastatic unfavorable-risk prostate cancer. Patients were randomized 1:1 to receive androgen deprivation therapy, radiation therapy, and docetaxel versus androgen deprivation therapy and radiation therapy. The study assessed the cumulative incidence rates of grade 2 and grade 3 or higher gastrointestinal, genitourinary, and sexual toxicity. A multivariable Fine and Gray's competing risks regression model adjusted for age at randomization and pelvic lymph node radiation therapy was used to evaluate the treatment effect of docetaxel on time to late genitourinary and gastrointestinal toxicities. The study included 338 patients who primarily had minimal or no comorbidity (74.9%) and median age 66 years (interquartile range: 61,71). At a median follow-up of 10.2 years, docetaxel was not associated with increased risk of any grade 3 or higher (adjusted hazard ratio [AHR], 0.98; 95% confidence interval [CI], 0.36-2.67; p=.96) or grade 2 gastrointestinal (p=.75), genitourinary (p=.44), and sexual (p=.29) toxicity. Age was associated with increased grade 3 or higher (AHR, 1.08; 95% CI, 1.01-1.16; p=.03) and grade 2 gastrointestinal toxicity (AHR, 1.11; 95% CI, 1.03-1.20; p=.005). A nonsignificant trend (p=.09) toward increased late grade 3 or higher toxicity was observed for pelvic radiation therapy use. Docetaxel combined with radiotherapy has an acceptable long-term toxicity profile.

Simultaneous Focal Boost With Stereotactic Radiation Therapy for Localized Intermediate- to High-Risk Prostate Cancer: Primary Outcomes of the SPARC Phase 2 Trial

Purpose: Dose escalated radiotherapy is associated with better biochemical control at the expense of toxicity. Stereotactic body radiotherapy (SBRT) with dose escalation to the dominant intraprostatic lesion (DIL) provides a logical approach to improve outcomes in high-risk disease whilst limiting toxicity. This study evaluated the toxicity and quality of life (QOL) with CyberKnife-based SBRT and simultaneous integrated boost in localised prostate cancer. Methods and Materials: Eligible participants included newly diagnosed, biopsy-proven unfavourable intermediate to high risk localised prostate cancer (at least one of the following: Gleason ≥ 4+3, MRI defined T3a N0, PSA ≥ 20) with up to two MRI-identified DILs. Participants received 36.25Gy in 5 fractions on alternative days with a simultaneous boost to DIL up to 47.5Gy as allowed by organs at risk constraints delivered by CyberKnife. All participants received androgen deprivation therapy. The primary outcome measure was acute grade 2 + genitourinary toxicity. Acute and late genitourinary and gastrointestinal toxicity using RTOG scoring, biochemical parameters, IPSS, IIEF5, EQ5D QOL outcomes were assessed. Results: Between 2013 and 2023, 20 participants were enrolled with a median follow-up of 30 months. The median D95 dose to DIL was 47.43Gy. Cumulative acute grade 2 + genitourinary and gastrointestinal toxicity was 25% and 30%, respectively. One patient developed acute grade 3 genitourinary toxicity (5%). There is no late grade 3 genitourinary or gastrointestinal toxicity to date. IPSS score and urinary QOL scores recovered to baseline by 6months. Patient-reported outcomes showed no significant change in EQ-5D QOL scores at 12 weeks and 1 year. There are no cases of biochemical relapse reported to date. Conclusions: CyberKnife SBRT delivered dose of 36.25Gy to the prostate with a simultaneous integrated boost up to 47.5Gy is well tolerated. Acute and late GU and GI toxicity rates are comparable to other contemporary SBRT trials and series with focal boost.

Low Social Well-Being in Advanced and Metastatic Prostate Cancer: Effects of a Randomized Controlled Trial of Cognitive Behavioral Stress Management.

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. 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, 6months, and 12months. Covariates were included in all models as appropriate. 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- (6months) and long-term (12months). 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. As predicted, the CBSM intervention improved several affect-based psychosocial outcomes for APC survivors with low baseline SWB.

Variation in Access to Palliative Radiotherapy in Prostate Cancer: A Population-Based Study in Canada.

As a result of improvements in cancer therapies, patients with metastatic malignancies are living longer, and the role of palliative radiotherapy has become increasingly recognized. However, access to adequate palliative radiotherapy may continue to be a challenge, as is evident from the high proportion of patients dying of prostate cancer who never receive palliative radiotherapy. The main objective of this investigation is to identify and describe the factors associated with the receipt of palliative radiation treatment in a decedent cohort of prostate cancer patients in Ontario. Population-based administrative databases from Ontario, Canada, were used to identify prostate cancer decedents, 65 years or older who received androgen deprivation therapy between January 1, 2013, and December 31, 2018. Baseline and treatment characteristics were analyzed using univariate and multivariate logistic regression models for association with receipt of radiotherapy in a two-year observation period before death. We identified 3,788 prostate cancer decedents between 2013 and 2018; among these, 49.9% received radiotherapy in the two years preceding death. There were statistically significant positive associations between receipt of radiotherapy and younger age at diagnosis (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.3); higher stage at diagnosis (OR 1.3, 95% CI 1.1-1.7); receipt of care at a regional cancer center (OR 1.8, 95% CI 1.3-2.4); and involvement of radiation oncologists (OR 155.1, 95% CI 83.3-288.7)or medical oncologists (OR 1.4, 95% CI 1.1-1.8). However, there were no associations between receipt of radiotherapy and income, distance to the nearest cancer center, involvement of urologists in cancer care, healthcare administrative region, home-care involvement, or number of hospitalizations in the observation period. We found the utilization of palliative radiotherapy for prostate cancer patients in Ontario varies depending on age, stage at diagnosis, number of comorbidities, registration at regional cancer centers, and involvement of oncologists. There were no differences detected based on incomeor distance from a cancer center. The findings of this study represent an important opportunity to facilitate better access to palliative radiotherapy and referrals to multidisciplinary regional cancer centers, to improve the quality of life of this patient population.

(049) Prevalence of Erectile Dysfunction in Men with Stress Urinary Incontinence After Radical Prostatectomy

Abstract Introduction Stress urinary incontinence (SUI) and erectile dysfunction (ED) are significant complications that have a negative impact on patients' quality of life following radical prostatectomy (RP). Objective This study aimed to assess the prevalence of ED in men with SUI who underwent RP the first year after RP. Methods This study included men who underwent RP and followed up for 1 year post-surgery. Men who received androgen deprivation therapy (ADT) or radiation therapy before or after RP were excluded. We performed a descriptive assessment of demographics, comorbidities, erectile function (EF), laboratory, surgical pathology, and nerve-sparing status (NSS). Post-op SUI was described based on the number of pads used per day, categorized as 0 to 1 pad per day (continent or mild/social SUI), 2 pads per day (moderate SUI), and ≥ 3 pads per day (severe SUI) at 3, 6, and 12 months post-RP. ED was described based on IIEF score as normal EF normal (≥24), mild ED (18-23), moderate ED (11-17), and severe ED (≤10) at 3, 6, and 12 months post-RP. We reported the prevalence of ED among men with SUI during the first year after RP. We assessed if the severity of the SUI was a predictor of severe ED in a multivariable logistic regression model at 3, 6, and 12 months post-RP. Factors entered into the model included: patient age, number of comorbidities (≥ 3), NVB status (both resected), pre-RP EF, PDE5i exposure post-RP (yes), and severe SUI (≥ 3 pads per day). Results 9953 men were included in this study, with a median age of 62 (56, 67). The median number of comorbidities was 1 (0, 2). 10% had diabetes, 27% obstructive sleep apnea, and 19% reported 3 or more comorbidities. Preoperative median PSA was 5.7 ng/ml, with a median Gleason grade of 2 (2, 3).73% had Bilateral NSS, 20% unilateral, and 7% had both sides resected. The prevalence of severe ED was higher among men with severe SUI compared to men with 0 to 1 pad per day at 3, 6, and 12 months post-RP. At 3 months, men with 0 to 1 pad per day reported 31% no/mild ED and 59% severe ED, vs. men with severe SUI described 18% no/mild ED and 75% severe ED (p-value <0.001). At 6 months, for men with continence/mild SUI, 35% described no/mild Ed and 51% severe ED vs. men with severe SUI who had 20% no/mild ED and 70% severe ED (p-value <0.001). And at 12 months, men with 0 to 1 pad per day reported 42% no/mild ED and 46% severe ED, vs. men with severe SUI described 22% no/mild ED and 70% severe ED (p-value <0.001). In the multivariable regression model, severe SUI significantly predicted severe ED at 3, 6, and 12 months (Table1). Conclusions Men experiencing severe SUI have a high prevalence of severe erectile dysfunction. Severe SUI significantly predicted severe ED during the first year following RP. Disclosure No.

A novel cardiovascular disease risk score for prediction of atherosclerotic disease events in men with prostate cancer.

314 Background: Prostate cancer patients (PC) face an elevated risk of both developing atherosclerotic cardiovascular disease (ASCVD). The American College of Cardiology Pooled Cohort Equations (PCE) for ASCVD predictions may lack accuracy. Methods: Males ≥18 years, diagnosed with PC between 2005-2012 at a hybrid academic-community practice were included. Using XGBoost algorithm we developed using a training subset of the cohort (50% train + 25% test), ranked 33 covariates (including demographic, treatment-related and social determinants of health (SDOH) information) for ASCVD prediction using SHAP (Shapley additive explanations) values. The top 10 predictors were transformed in a predictive equation using logistic regression models. This equation was tested in the cohort validation subset (25%), and subsequently compared to the PCE risk score. Results: We included 1,506 patients, with a median age of 67 (IQR 60-74) years, 13.8% had advanced stage disease (TNM III-IV), 1.5% had high risk PC (Gleason 8-10), and 20.5% received androgen deprivation therapy (ADT). Of those, 10.4% had a 10-year ASCVD risk. The PCE had an area under the curve (AUC)=0.61 and underestimated ASCVD in 0.9% (mean risk=20.1% [95% CI 17.2-23.0] vs. mean predicted risk=19.2% [95% CI 18.6-19.8]). The equation pooled from the top-10 predictors of the ML algorithm (C-index=0.78 [95% CI 0.75-0.81]) achieved an AUC=0.71 (Table). Conclusions: Conventional PCE tend to underestimate ASCVD risk in males with PC. A cancer-specific model inclusive of SDOH exhibits good performance for predicting ASCVD risk in this population. [Table: see text]

Optimal sequential therapy for metastatic castration-resistant prostate cancer after androgen receptor pathway inhibitors in the up-front era.

168 Background: The optimal sequential therapy for metastatic castration-resistant prostate cancer (mCRPC) following the use of up-front androgen receptor pathway inhibitors (ARPIs) for metastatic hormone-sensitive prostate cancer (mHSPC) is still unclear. Methods: A total of 220 patients who received systemic therapy for de novo mHSPC at Nagoya University Hospital and its affiliated institutions between 2014 and 2022 were included in the study. Patients who received up-front therapy with ARPI as first-line therapy for mHSPC, followed by ARPI as primary therapy for mCRPC were defined as the AA group, followed by docetaxel (DOC) as primary therapy for mCRPC were defined as the AD group. On the other hand, the vAA group was defined as patients who received androgen deprivation therapy alone or combined androgen blockade as “vintage” first-line therapy for mHSPC, followed by two consecutive ARPIs as sequential therapy for mCRPC, and the vAD group was defined as patients who received ARPI followed by DOC as sequential therapy for mCRPC. Patient characteristics and progression-free survival (PFS) of the second agent after the first ARPI were compared in each group. Results: We identified 14 patients in the AA group, 16 in the AD group, 84 in the vAA group, and 59 in the vAD group. There were no differences in patient background such as initial PSA, Gleason score, and metastatic burden between the groups, while patient age was lower in the AD and vAD groups compared to the AA and vAA groups. The PFS of the second agent in the AA group was significantly shorter than that in the vAA group (median, 6.8 vs. 1.9 months; hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.25-0.87; p=0.017). In contrast, there was no significant difference in PFS of the second agent in the vAD and AD groups (median, 7.0 vs. 4.0 months; HR, 0.63; 95%CI, 0.29-1.34; p=0.235). Conclusions: The effect of each agent after ARPI therapy in the UP-FRONT era may be poorer than that in the VINTAGE era. In the setting after up-front ARPI, sequential therapy with DOC may be more appropriate than sequential therapy with ARPI.

11-Ketotestosterone and time to castration resistance in patients with recurrent non-metastatic prostate cancer receiving androgen deprivation therapy.

209 Background: The contribution of 11-oxygenated androgens to disease progression in men receiving androgen deprivation therapy (ADT) for recurrent non-metastatic prostate cancer (PCa) remains unresolved. We hypothesized that evaluating circulating levels of 11-oxygenated androgens, such as the potent androgen receptor (AR) agonist 11-ketotestosterone (11KT), could serve as a potential predictor for the onset of castration resistance (CRPC). Methods: The multi-institutional prospective PROCURE cohort involves 2,026 patients who underwent radical prostatectomy for localized PCa. In this cohort, a subset of 145 patients who received ADT therapy for recurrent disease and had available plasma samples post-surgery were included in this study. The effect of therapy on steroid levels was assessed in paired samples obtained before and after the initiation of ADT (n=50), and samples from patients under combined ADT with AR pathway inhibitors, enzalutamide (n=10) and abiraterone (n =15). 11-oxygenated androgens (n=7) and canonical steroids, such as testosterone (T) and dihydrotestosterone (DHT), were quantified by mass spectrometry. Kaplan-Meier survival analyses were used to investigate relationships of androgen levels with the occurrence of CRPC. Results: 11-oxygenated androgens remained unaffected by ADT, which stands in contrast to the observed changes in T, DHT and other steroids. In men with castrated T levels, 11KT was the most abundant androgen. Elevated 11KT was associated with a sooner time to CRPC ( P=0.023). The 10-year CRPC event-free rate was 63% vs. 84% for 11KT levels above and below the median, respectively. The initiation of enzalutamide had no impact on 11-oxygenated androgen levels, whereas abiraterone significantly reduced 11KT levels owing to the adrenal origin of its precursor. Conclusions: Our findings indicate that 11KT is a significant component of the hormonal profile predictive of an earlier onset of CRPC and inhibition of its production by the CYP17A1 inhibitor abiraterone.

Understanding variation in treatment intensification for de novo metastatic castration-sensitive prostate cancer (mCSPC): A population-based cohort study.

69 Background: Treatment intensification using androgen receptor signaling inhibitors (ARSIs) or chemotherapy is guideline-recommended for patients with mCSPC based on improved survival and preserved quality of life. However, numerous studies across jurisdictions have shown relatively limited uptake, with most patients receiving androgen deprivation therapy (ADT) monotherapy. Therefore, we sought to understand patient, physician, and tumor characteristics associated with treatment intensification. Methods: This population-based cohort study in Ontario, Canada included older men (age ≥66 years) diagnosed with de novo mCSPC between Jan 2014 and Nov 2021 for whom the ADT-prescribing physician could be identified (>99.5% of all mCSPC patients). We used hierarchical regression modelling to assess the association (presented as odds ratio, OR) between patient sociodemographic characteristics and comorbidities, tumor characteristics, and physician characteristics with receipt of intensified treatment for mCSPC, defined as receipt of an ARSI, docetaxel, or both within 6mo. We used Darlington’s method to assess the relative importance of these predictors (presented as standardized regression coefficients, SRC). Results: Among 4450 eligible older men newly diagnosed with de novo mCSPC, 18.8% received treatment intensification, with rates increasing from 6.3% in 2014 to 31.9% by 2021. In multivariable modeling, patient age was the most influential variable, with older patients significantly less likely to receive treatment intensification (SRC -43.8, OR 0.91, 95% CI 0.90-0.92). Socioeconomic status (SRC -12.2; OR 0.54, 95% CI 0.33-0.88 for quintile 1 vs 5) and a history of stroke (SRC -11.5, OR 0.28, 95% CI 0.09-0.86), but no other patient factors including comorbidity, were significantly associated with intensification. Patients prescribed ADT for mCSPC by radiation oncologists were less likely to receive intensification (SRC -16.5; OR 0.47, 95% CI 0.23-0.95) compared to other providers without significant differences between patients treated by urologists, medical oncologists, or other physicians. No other physician-level characteristic (age, sex, years in practice, or annual volume of prostate cancer patients) was associated with treatment intensification. More contemporary year of diagnosis was also strongly predictive (mean SRC 31.2) of intensification. We noted significant geographic variation (mean SRC 10.2; p<0.0001), that could not be explained by rurality (p=0.08) and persisted after adjustment for socioeconomic status and patient characteristics. Conclusions: Patient, disease, and physician characteristics contribute to variation in treatment intensification for mCSPC. These data may allow focused intervention to improve guideline-concordant care for patients with mCSPC.

Prevalence of Preexisting Cardiovascular Diseases in Prostate Cancer Patients and Cardiac Risks of Hormonal Therapy.

Cardiovascular diseases (CVDs) are a prominent cause of mortality in prostate cancer patients. However, it has been reported that patients with preexisting CVDs are at greater risk. Literature on the magnitude of this problem in Saudi Arabia is lacking. To measure the prevalence of prostate cancer patients with preexisting CVDs in our population and to elucidate the possible risk factors of new cardiovascular events (CVEs) in patients who received androgen deprivation therapy (ADT). This retrospective study included all patients newly diagnosed with prostate cancer at a tertiary hospital in the Eastern Province of Saudi Arabia from October 2008 to January 2019. The prevalence of preexisting cardiovascular diseases in these patients were determined. In addition, the incidence of new CVEs after initiating ADT was determined along with the risk factors for the same. The prevalence of preexisting CVD in our cohort was 16%. About 6% of the patients who received ADT had CVEs after a median follow-up of 39 months (IQR: 11-49 months). In the univariate analysis, hyperlipidemia (P = 0.002), stroke (P = 0.001), peripheral vascular disease (P = <0.001), cardiac patients with stents (P = <0.001), and cardiac patients without stent (P = <0.001) were significant risk factors of new CVEs after initiating ADT. However, in the multivariate regression analysis, only history of stroke and CVD (with or without stent) were found to be significant risk factors of new CVEs after initiating ADT (P = 0.01). About one-fifth of the prostate cancer patients had preexisting CVDs. This study also found that luteinizing hormone-releasing hormone agonist could be a risk factor for new CVEs.

Outcomes in patients with high- and very high-risk localized prostate cancer treated with definitive IMRT and long-term hormone therapy.

The aim of this study was to evaluate the effectiveness of intensity-modulated radiation therapy in combination with long-term androgen deprivation therapy for high-risk and very high-risk localized prostate cancer while also investigating factors associated with the therapeutic effect. Men who fulfilled criteria for the National Comprehensive Cancer Network high-risk or very high-risk localized prostate cancer and were treated with definitive intensity-modulated radiation therapy (74-78Gy) of the prostate and the seminal vesicle combined with androgen deprivation therapy in our institution from 2007 to 2016 were identified (n=197). In principle, patients received androgen deprivation therapy for 3-6months before radiation, concurrently, and for 2years after completion of intensity-modulated radiation therapy. The median follow-up period was 96months. The 5-year and 10-year overall survival rates in the overall population were 96.9% and 89.3%, respectively. The 5-year and 10-year cumulative incidence rates of biochemical failure were 2.5% and 16.3% in the high-risk group, and 8.6% and 32.0% in the very high-risk group, respectively, indicating a significant difference between the two groups (P=0.023). Grade Group 5 and younger age (cutoff: 70years old) were independent predictors of recurrence (P=0.016 and 0.017, respectively). Patients exhibiting biochemical failure within <18months after completion of androgen deprivation therapy displayed an increased risk of cancer-specific mortality (P=0.039) when contrasted with those who had a longer interval to biochemical failure. Patients with the National Comprehensive Cancer Network very high-risk prostate cancer, particularly those with Grade Group 5 and younger age, showed worse outcomes following intensity-modulated radiation therapy and long-term androgen deprivation therapy.

Statin use and mortality risk in Asian patients with prostate cancer receiving androgen deprivation therapy: A population-based cohort study.

This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow-up conducted until September 2021. Patients who had received medical castration for <180 days without subsequent bilateral orchidectomy, those who had used statins concurrently with ADT for <180 days, and those with missing baseline total cholesterol levels were excluded. Statin users were defined as individuals who had used statins for ≥180 days concurrent with ADT, while non-users were those who had not used any statins. PCa-related mortality was the primary outcome, while all-cause mortality served as the secondary outcome. Inverse probability treatment weighting was employed to balance the covariates. A total of 4920 patients were included, consisting of 2578 statin users and 2342 non-users (mean age 76.1 ± 8.2 years). Over a mean follow-up period of 4.2 ± 3.3 years, it was observed that statin users had significantly lower risks of both PCa-related mortality (weighted hazard ratio [wHR] 0.56 [95% confidence interval (CI) 0.48, 0.65], p < 0.001) and all-cause mortality (wHR 0.57 [95% CI 0.51, 0.63], p < 0.001), regardless of the type of ADT used. Notably, these associations were more pronounced among patients with less advanced PCa, as indicated by the absence of androgen receptor antagonist or chemotherapy usage (p value for interaction <0.001 for both outcomes). The use of statins concurrent with ADT was associated with reduced mortality risks among Asian patients with PCa. These findings suggest the need for additional research to explore the potential role of statins in the treatment of PCa patients.

Prostate-specific antigen (PSA) decline with apalutamide therapy is associated with longer survival and improved outcomes in individuals with metastatic prostate cancer: a plain language summary of the TITAN study.

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. In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes. 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.

Is Ultrahypofractionated Whole Pelvis Radiation Therapy (WPRT) as Well Tolerated as Conventionally Fractionated WPRT in Patients With Prostate Cancer? Early Results From the HOPE Trial

ObjectiveTo evaluate acute toxicity and quality of life (QOL) impact of ultra-hypofractionated whole pelvis radiotherapy (WPRT) compared to conventional WPRT fractionation post high-dose rate (HDR) prostate brachytherapy (BT). MethodsBLINDED FOR REVIEW is a phase 2, multi-institutional randomized controlled trial involving men with prostate-confined disease and NCCN unfavorable intermediate, high, or very-high-risk prostate cancer. Patients were randomly assigned to receive conventionally fractionated WPRT (standard arm) or ultra-hypofractionated WPRT (experimental arm) in a 1:1 ratio. All patients underwent radiotherapy with 15 Gy HDR-BT boost in a single fraction followed by WPRT delivered with conventional fractionation (45 Gy in 25 daily fractions or 46 Gy in 23 fractions) or ultra-hypofractionation (25 Gy in 5 fractions delivered on alternate days). Acute toxicities, measured during radiotherapy and at 6 weeks post-treatment, were assessed using the clinician-reported Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and QOL was measured using the Expanded Prostate Cancer Index Composite (EPIC-50) and International Prostate Symptom Score (IPSS). ResultsA total of 80 patients were enrolled and treated across three Canadian institutions. A total of 39 and 41 patients received external radiotherapy with conventionally fractionated and ultra-hypofractionated WPRT, respectively. All patients received androgen deprivation therapy, except for 2 patients treated in the ultra-hypofractionated arm. Baseline clinical characteristics were similar between the two arms, with 51 (63.8%) patients having high or very high-risk prostate cancer disease. Treatment was well tolerated with no significant differences in the rate of acute adverse events between arms. No grade 4 adverse events or treatment-related deaths were reported. Ultra-hypofractionated WPRT had a less detrimental impact in the EPIC-50 bowel total, function and bother domain scores when compared to conventional WPRT in the acute setting. On the contrary, more patients treated with ultra-hypofractionated WPRT reached the minimum clinical important difference on EPIC-50 urinary domains. No significant QOL differences between arms were noted in the sexual and hormonal domains. ConclusionUltra-hypofractionated WPRT following HDR-BT is a well-tolerated treatment strategy in the acute setting and leads to less detrimental impact on bowel QOL domains when compared to conventional WPRT.

A comparison of aerobic- and resistance-emphasised exercise on cardiometabolic health and quality of life in men receiving androgen deprivation therapy for prostate cancer: Protocol for a feasibility trial

BackgroundThose with intermediate and high-risk prostate cancer typically receive androgen deprivation therapy (ADT) as part of their treatment. ADT often results in extensive side effects including increased risk of cardiometabolic disease. Many ADT side effects can be influenced by exercise, both resistance and aerobic training. Exercise regimes typically combine aerobic and resistance exercise but the appropriate emphasis for achieving the broadest range of therapeutic benefits has yet to be determined. We propose to determine the feasibility of undertaking a larger trial comparing a resistance- vs an aerobic-emphasised exercise intervention in men with prostate cancer undergoing ADT. The trial will also investigate preliminary evidence of difference between arms for cardiometabolic health and quality of life outcomes. MethodsThis is a 6-month randomised two-armed feasibility trial. Prostate cancer patients undergoing ADT and radiotherapy will be recruited (n = 24) and randomised to either a resistance- or aerobic-emphasised group. Participants will attend twice-weekly supervised individual or small group sessions, with 75% of exercise time in the primary exercise modality. The primary outcome will be feasibility, determined via assessment of recruitment, retention, adherence, safety, and acceptability. Secondary outcomes will include quality of life, body composition, vascular indices, aerobic and muscular fitness and cardiometabolic health blood biomarkers. ConclusionIt is envisaged that the trial will provide valuable information and preliminary difference data that will aid in the design of an efficacious larger trial that will adopt a major and minor emphasis approach to the scheduling of resistance and aerobic exercise.