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Purpose: No study has compared cancer regression (d) and growth (g) rates in patients with advanced castration-sensitive prostate cancer (CSPC) treated with androgen deprivation therapy. The comparison of d and g rates provides insight into the differential impact of ADT regimens on tumor dynamics, potentially guiding more personalized treatment strategies. Therefore, we aimed to estimate these rates and evaluate their impact on survival outcomes. Methods: Sequential prostate-specific antigen (PSA) data was obtained from the KYUCOG-1401 trial including patients with advanced CSPC randomized to gonadotropin-releasing hormone (GnRH) antagonist (group A) and GnRH agonist plus bicalutamide (group B). d and g rates were estimated by applying mathematical models and were compared in subgroups. PSA-progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were compared by lower and higher than the median of these rates. Results: Patients with higher PSA and higher extent of disease score at enrollment presented higher d rates (0.03965 vs. 0.03546, p = 0.0006) and (0.03947 vs. 0.03587, p = 0.0113) for groups A and B, respectively. The median d rate was lower for group A than group B (0.03306 vs. 0.039965, respectively [p = 0.0002]). The median g rate was higher for group A than group B (0.00016 vs. 0.00002, respectively [p = 0.0014]). The g rate, but not the d rate discriminated PSA-PFS, rPFS, and OS. Conclusion: Our results suggest that GnRH agonist plus bicalutamide reduced PSA level faster and suppressed PSA rising longer than GnRH antagonist. Moreover, measuring the g rate can predict PSA-PFS, rPFS, and OS in patients with advanced CPSC treated with androgen deprivation therapy. These findings suggest that incorporating g rate measurements into clinical practice could improve prognostic accuracy and guide treatment decisions in advanced CSPC. [ABSTRACT FROM AUTHOR]

Prostate cancer is a common and serious disease among American men, but it has a high survival rate when detected early. This editorial discusses the factors that contribute to the progression of prostate cancer and its lethality, including abnormalities in the androgen receptor pathway, microRNA, and the bony microenvironment. The authors suggest potential targets for therapy to improve survival in men with advanced prostate cancer. The document also includes information about funding and conflicts of interest, as well as a disclaimer that the views expressed are solely those of the authors. References to other articles and studies on prostate cancer treatment are provided. [Extracted from the article]

Objectives Methods Results Conclusion The objective of this study is to assess the trends in treatment selection for patients with de novo metastatic castration‐sensitive prostate cancer in the era of upfront combination therapy.This multicenter retrospective study included 595 patients treated with either upfront combination therapy (upfront novel hormonal therapies and taxane‐based chemotherapy) or vintage therapy (androgen deprivation therapy with or without bicalutamide) between 2016 and 2021. High tumor burden metastatic disease was defined when a patient met the CHAARTED or LATITUDE criteria. We evaluated trends in treatment selection and reasons for selecting vintage therapy.Of the 595, 123 and 472 patients were classified as having low and high tumor‐burden disease, respectively. The Use of upfront combination therapy was found to be rapidly increasing with utilization rates of 72% and 54% in 2021 for high and low tumor‐burden disease, respectively. Multivariable logistic regression analysis found older age, poor performance status, and nonacademic center were significantly associated with the selection of vintage therapy. Of the 163 patients who received vintage hormone therapy after approval of upfront therapy, 74.2% had a specific reason for avoiding upfront therapy. The reasons for selecting vintage therapy included refusal (39.8%), older age (67.6%), frailty (56.3%), and comorbidity (40.8%). Furthermore, 16.9% of patients declined upfront combination therapy due to cost concerns.Upfront combination therapy use has 72% and 54% prevalence among patients with high and low tumor burden diseases, respectively, in this current practice. Older age, poor performance status, and facility bias were negatively associated with the use of upfront combination therapy. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to explore the evolving landscape of treatments available for metastatic castration-sensitive prostate cancer (mCSPC) patients. Recent Findings: In less than a decade, evidence was chronologically provided that (1) systemic treatment intensification with docetaxel improves outcomes, including survival, in men with mCSPC, (2) then that these outcomes are also improved when a second-generation androgen receptor pathway inhibitor (ARPI) is combined with androgen deprivation therapy (ADT), and (3) using a "triplet systemic therapy," which consists in the combination of ADT, an ARPI and docetaxel, further improves outcomes, including survival. Radiotherapy to the prostate combined with ADT alone is now recommended in men with low-volume mCSPC. Combining prostate radiotherapy and intensified systemic treatment including abiraterone may be synergistic as suggested in the PEACE-1 trial. Also, the role of metastases-directed local therapies (mostly stereotactic radiotherapy) is currently being assessed in phase 3 trials. Finally, the integration of biomarkers (e.g. BRCA2 gene alterations, PTEN loss, PSMA expression) for decision making is not currently established, though trials are also currently underway. Importantly, most evidence currently available was obtained in men with de novo metastases, while for those with metastatic relapse after definitive local treatment, the role of treatment intensification is less well established. Summary: Treatment intensification is nowadays the standard of care for patients with de novo mCSPC as it leads to outcomes improvement, including survival, and the standard of care is evolving almost on a yearly basis. [ABSTRACT FROM AUTHOR]

Background and aims: A gonadotropin-releasing hormone (GnRH)-based therapeutic vaccine candidate against hormone-sensitive prostate cancer has demonstrated its safety and signs of efficacy in phase I/II trials. In this study, we characterized the isotype/subclass profiles of the anti-GnRH humoral response generated by the vaccination and analyzed its association with patients' clinical outcomes. Methods: The immunoglobulin isotypes and IgG subclasses of the antibody responses of 34 patients included in a randomized, open, prospective phase I/II clinical trial were characterized. Every patient included in the study had a diagnosis of locally advanced prostate adenocarcinoma at stages 3 and 4 and received immunization with the vaccine candidate. Additionally, serum testosterone and prostate specific antigen (PSA) concentrations, serving as indicators of tumor response, were determined. The type of anti-GnRH antibody response was correlated to the time elapsed until the first biochemical recurrence in patients and the outcome of the disease. Results: All patients developed strong and prolonged anti-GnRH antibody responses, resulting in a short- to mid-term decrease in serum testosterone and PSA levels. Following immunizations, anti-GnRH antibodies of the IgM/IgG and IgG1/IgG3 subclasses were observed. Following radiotherapy, the humoral response switched to IgG (IgG1/IgG4). Patients who experienced a short-term biochemical relapse were characterized by significantly higher levels of anti-GnRH IgG titers, particularly IgG1 and IgG4 subclasses. These characteristics, along with a high response of specific IgM antibodies at the end of immunizations and the development of anti-GnRH IgA antibody responses following radiotherapy, were observed in patients whose disease progressed, compared to those with controlled disease. Conclusion: The nature of the humoral response against anti-GnRH, induced by vaccination may play a key role in activating additional immunological mechanisms. Collectively, these mechanisms could contribute significantly to the regulation of tumor growth. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most common cancer in men in the western world, but the lack of specific and sensitive markers often leads to overtreatment of prostate cancer which eventually develops into castration-resistant prostate cancer (CRPC). Novel protein markers for diagnosis and management of CRPC will be promising. In this review, we systematically summarize and discuss the expression pattern of emerging proteins in tissue, cell lines, and serum when castration-sensitive prostate cancer (CSPC) progresses to CRPC; focus on the proteins involved in CRPC growth, invasion, metastasis, metabolism, and immune microenvironment; summarize the current understanding of the regulatory mechanisms of emerging proteins in CSPC progressed to CRPC at the molecular level; and finally summarize the clinical applications of emerging proteins as diagnostic marker, prognostic marker, predictive marker, and therapeutic marker. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most common cancer in men in the western world, but the lack of specific and sensitive markers often leads to overtreatment of prostate cancer which eventually develops into castration-resistant prostate cancer (CRPC). Novel protein markers for diagnosis and management of CRPC will be promising. In this review, we systematically summarize and discuss the expression pattern of emerging proteins in tissue, cell lines, and serum when castration-sensitive prostate cancer (CSPC) progresses to CRPC; focus on the proteins involved in CRPC growth, invasion, metastasis, metabolism, and immune microenvironment; summarize the current understanding of the regulatory mechanisms of emerging proteins in CSPC progressed to CRPC at the molecular level; and finally summarize the clinical applications of emerging proteins as diagnostic marker, prognostic marker, predictive marker, and therapeutic marker.

In recent years, randomized controlled trials have demonstrated that upfront androgen receptor signaling inhibitors (ARSIs) prolong overall survival (OS) compared with androgen deprivation therapy (ADT) alone or combined androgen blockade (CAB) in patients with metastatic castration-sensitive prostate cancer (mCSPC). However, it remains unclear whether upfront ARSI is superior to CAB in Asian populations, among which the efficacy of ADT/CAB is considered relatively high. In this study, we compared the oncological outcomes of upfront ARSI and CAB in Japanese patients with mCSPC. Patients with mCSPC who underwent systemic therapy between May 2009 and October 2023 were enrolled retrospectively. Propensity score matching (PSM) was performed to compare the castration-resistant prostate cancer-free survival (CRPC-FS), cancer-specific survival (CSS), and OS between patients treated with upfront ARSI (ARSI group) and those treated with CAB (CAB group). In total, 30 and 142 patients were enrolled in the ARSI and CAB groups, respectively. After PSM (25 patients in each group), CRPC-FS was significantly longer in the ARSI group than in the CAB group (median: 36.7 vs. 12.3 months, hazard ratio: 0.44, 95% confidence interval: 0.20-0.97, p = 0.035). No significant differences were observed in CSS or OS between the two groups. In conclusion, when compared to CAB, upfront ARSI might have the potential to extend CRPC-FS among individuals in the Japanese population., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Androgen deprivation therapy (ADT) combined with apalutamide, abiraterone acetate plus prednisone, enzalutamide, or docetaxel are the standard treatments for advanced castration-sensitive prostate cancer (CSPC). We investigated ADT-free alternatives for advanced CSPC. LACOG 0415 is a phase 2, open-label, non-comparative, randomized trial. Patients with advanced CSPC were randomized (1:1:1) to receive goserelin plus abiraterone acetate and prednisone (ADT plus AAP arm), apalutamide (APA arm), or apalutamide plus abiraterone acetate and prednisone (APA plus AAP arm). The primary endpoint was the proportion of patients with PSA of ≤0.2 ng/mL at week 25 in the modified intention-to-treat population. Safety analyses were performed in all patients with at least one dose of the study drug. Of 128 randomized patients, 120 patients were evaluable for PSA response at week 25; 17.2% had a high-risk biochemical recurrence, 8.6% had locally advanced disease, and 74.2% had distant metastases. At week 25, PSA of ≤0.2 ng/mL was observed in 75.6% (95%CI 59.7%–87.6%), 60.0% (95%CI 43.3%–75.1%), and 79.5% (95%CI 63.5%–90.7%) of patients in ADT plus AAP, APA, and APA plus AAP arms, respectively. PSA decline of ≥80% was observed in 100%, 90.0%, and 97.4%, respectively. Grade 3–4 AEs were observed in 31.0%, 21.4% and 36.4%, respectively. Testosterone levels increased significantly in the APA arm and decreased significantly in ADT plus AAP and APA plus AAP arms. ADT-free alternatives provide a high PSA response in advanced CSPC, although the APA arm did not reach the expected rate of PSA of ≤0.2 ng/mL at week 25. These results warrant further investigation of ADT-free treatments as alternatives in advanced CSPC. ClinicalTrials.gov NCT02867020. • ADT-free alternatives provide high PSA response in advanced CSPC. • Although the APA arm did not reach the expected rate of PSA of ≤0.2 ng/mL at week 25. • The three arms had a distinct toxicity profile and similar HRQoL. [ABSTRACT FROM AUTHOR]

Background: Docetaxel (DOC) and abiraterone (ABI) in the upfront setting have separately improved clinical outcomes for metastatic hormone‐sensitive prostate cancer (mHSPC), but there are no studies comparing drug efficacies or the influence of racial disparities. Materials and Methods: We performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014–2020) for patients with mHSPC treated with either upfront DOC or ABI. Outcomes evaluated were overall survival (OS), progression‐free survival (PFS), and prostate‐specific antigen complete response (PSA CR). Results: A total of 168 patients were included, consisting of 92 (54.8%) Black patients and 76 (45.2%) non‐Black patients (69 White and 7 Asian or Hispanic). Ninety‐four (56%) received DOC and 74 (44%) received ABI. Median follow‐up time was 22.8 months with data last reviewed June 2020. For OS, there was no significant difference between ABI versus DOC and Black versus non‐Black patients. For PFS, DOC was associated with hazard ratio (HR) 1.7 compared with ABI for all patients based on univariate association and HR 2.27 compared with ABI for Black patients on multivariable analysis. For PSA CR, Black patients were less likely to have a CR (odds ratio [OR] = 0.27). Conclusion: ABI and DOC have similar OS with a trend toward better PFS for ABI in a cohort composed of 54% Black patients. Racial disparities were observed as prolonged PFS for Black patients treated with ABI, more so compared with all patients, and less PSA CR for Black patients. A prospective trial comparing available upfront therapies in a diverse racial population is needed to help guide clinical decision‐making in the era of novel treatment options. Implications for Practice: Overall survival is similar for abiraterone and docetaxel when used as upfront therapy in metastatic hormone‐sensitive prostate cancer in a cohort composed of 54% Black patients. There is a trend towards improved progression‐free survival for abiraterone in all patients and Black patients. Non‐Black patients were more likely to achieve prostate‐specific antigen (PSA) complete response regardless of upfront therapy. This article presents a retrospective review of 168 patients diagnosed with metastatic hormone‐sensitive prostate cancer who received upfront therapy with either docetaxel (DOC) or abiraterone (ABI), focusing on real‐world clinical outcomes and potential racial disparities. [ABSTRACT FROM AUTHOR]

Abstract Background Testosterone suppression is the standard treatment for advanced prostate cancer, and it is associated with side-effects that impair patients’ quality of life, like sexual dysfunction, osteoporosis, weight gain, and increased cardiovascular risk. We hypothesized that abiraterone acetate with prednisone (AAP) and apalutamide, alone or in combination, can be an effective hormonal therapy also possibly decreasing castration-associated side effects. Methods Phase II, open-label, randomized, efficacy trial of abiraterone acetate plus prednisone (AAP) and Androgen Deprivation Therapy (ADT) versus apalutamide versus the combination of AAP (without ADT) and apalutamide. Key eligibility criteria are confirmed prostate adenocarcinoma; biochemical relapse after definitive treatment (PSA ≥ 4 ng/ml and doubling time less than 10 months, or PSA ≥ 20 ng/ml); newly diagnosed locally advanced or metastatic prostate cancer; asymptomatic to moderately symptomatic regarding bone symptoms. Patients with other histology besides adenocarcinoma or previous use of hormonal therapy or chemotherapy were excluded. Discussion There is an urgent need to study and validate regimens such as new hormonal agents that may add benefit to castration with an acceptable safety profile. We aim to evaluate if apalutamide in monotherapy or in combination with AAP is an effective and safety hormonal treatment that can spare patients of androgen deprivation therapy. Trial registration This trial was registered in ClinicalTrials.gov on October 16, 2017, under Identifier: NCT02867020.

BACKGROUND International guidelines state that bone-targeted agents such as denosumab or zoledronic acid at doses used for bone metastasis are not indicated for patients with metastatic castration-sensitive prostate cancer (mCSPC) with bone metastases. Whereas denosumab has never been studied in this patient population, zoledronic acid has been shown to be ineffective in decreasing the risk for skeletal-related events. This study estimates the prevalence and economic consequences of real-world use of bone-targeted agents for mCSPC patients in Switzerland. METHODS To estimate the frequency of bone-targeted agent administration and skeletal-related events, data from a non-interventional, cross-sectional survey involving oncologists across Switzerland (SAKK 95/16) was combined with data from the Swiss National Institute for Cancer Epidemiology and Registration (NICER). Economic parameters were calculated from the perspective of the healthcare system over the median time to prostate-specific antigen (PSA) progression for the extrapolated patient group, using data from NICER. The cost calculation covered costs for bone-targeted agents, their administration and skeletal-related events. The time to PSA progression (33.2 months), as well as the probability and cost of skeletal-related events were derived from the literature. RESULTS The survey was answered by 86 physicians treating 417 patients, of whom 106 (25.4%) had prostate cancer, with 36 (34.0%) of these mCSPC. The majority of mCSPC patients (52.8%, n = 19) received bone-targeted agents monthly. Denosumab was the treatment of choice in 84.2% of patients (n = 16). Extrapolation using data from NICER indicated that 568 mCSPC patients may be treated with bone-targeted agents at doses used for bone metastasis every year in Switzerland, leading to estimated total costs of more than CHF 8.3 million over 33.2 months. Because of its more frequent prescription and higher price, it appears that almost 93% of the total costs can be attributed to denosumab. For both denosumab and zoledronic acid, the most expensive components were the cost of administration and the drug cost, making up more than 90% of the total costs, with the rest being costs of skeletal-related events. CONCLUSIONS This study found that the administration of bone-targeted agents in doses used for bone-metastatic diseases to prevent skeletal-related events is frequent in the setting of mCSPC and results in significant costs for the healthcare system.

Objective: To evaluate the efficacy and safety of apalutamide + androgen deprivation therapy versus androgen deprivation therapy alone in Japanese patients with metastatic castration‐sensitive prostate cancer from the phase 3, randomized, global TITAN study. Methods: Men with metastatic castration‐sensitive prostate cancer randomly (1:1) received 240 mg apalutamide + androgen deprivation therapy or matching placebo + androgen deprivation therapy. The primary efficacy endpoints were radiographic progression‐free survival and overall survival. Secondary efficacy endpoints were time to cytotoxic chemotherapy, pain progression, chronic opioid use, and skeletal‐related events. Safety was also assessed. Results: Of the 1052 patients included in the TITAN study, 51 (4.85%) were Japanese (apalutamide group, n = 28; placebo group, n = 23). In all, 81.8% of patients in the apalutamide and 71.8% in the placebo group did not experience radiographic progression or death, and the hazard ratio for radiographic progression‐free survival favored treatment with apalutamide (hazard ratio 0.712, 95% confidence interval 0.205–2.466; P = 0.59). At 24 months, 85.7% of patients in the apalutamide group and 81.5% in the placebo group were alive, and the hazard ratio for overall survival favored apalutamide (hazard ratio 0.840, 95% confidence interval 0.210–3.361; P = 0.805). In the interim analysis, the median radiographic progression‐free survival and overall survival were not reached in the apalutamide group and time to cytotoxic chemotherapy was delayed following apalutamide treatment. The safety profile of apalutamide in the Japanese subpopulation was comparable with that of the global population, except for skin rash. Conclusions: The results of the present analyses suggest that apalutamide + androgen deprivation therapy in Japanese patients had favorable efficacy compared with androgen deprivation therapy alone, and these findings are comparable to those in the overall population. Apalutamide + androgen deprivation therapy can be considered as one of the therapeutic options for a broad spectrum of metastatic castration‐sensitive prostate cancer regardless of prior treatment and disease extent in Japanese patients. [ABSTRACT FROM AUTHOR]

Background: Metastasis-directed therapy (MDT) is increasingly being used in oligometastatic castration-sensitive prostate cancer (omCSPC). However, it is currently unclear how to optimally integrate MDT with the standard of care of systemic hormonal therapy., Objective: To report long-term outcomes of MDT alone versus MDT and a defined course of androgen deprivation therapy (ADT) in omCSPC., Design, Setting, and Participants: Here, a multicenter, international retrospective cohort of omCSPC as defined by conventional imaging was reported., Outcome Measurements and Statistical Analysis: Biochemical progression-free survival (bPFS), distant progression-free survival (dPFS), and combined biochemical or distant progression-free survival (cPFS) were evaluated with Kaplan-Meier and multivariable Cox proportional hazard regression models., Results and Limitations: A total of 263 patients were included, 105 with MDT + ADT and 158 with MDT alone. The majority of patients had metachronous disease (90.5%). Five-year bPFS, dPFS, and cPFS were, respectively, 24%, 41%, and 19% in patients treated with MDT + ADT and 11% (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.36-0.64), 29% (HR 0.56, 95% CI 0.40-0.78), and 9% (HR 0.50, 95% CI 0.38-0.67) in patients treated with MDT alone. On a multivariable analysis adjusting for pretreatment variables, the use of ADT was associated with improved bPFS (HR 0.43, p < 0.001), dPFS (HR 0.45, p = 0.002), and cPFS (HR 0.44, p < 0.001)., Conclusions: In this large multi-institutional report, the addition of concurrent ADT to MDT appears to improve time to prostate-specific antigen progression and distant recurrence, noting that about 10% patients had durable control with MDT alone. Ongoing phase 3 studies will help further define treatment options for omCSPC., Patient Summary: Here, we report a large retrospective review evaluating the outcomes of metastasis-directed therapy with or without a limited course of androgen deprivation for patients with oligometastatic castration-sensitive prostate cancer. This international multi-institutional review demonstrates that the addition of androgen deprivation therapy to metastasis-directed therapy (MDT) improves progression-free survival. While a proportion of patients appear to have long-term disease control with MDT alone, further work in biomarker discovery is required to better identify which patients would be appropriate for de-escalated therapy., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Standard of care management for synchronous metastatic castration-sensitive prostate cancer (mCSPC) includes androgen deprivation therapy with a second-generation antiandrogen therapy and/or docetaxel. Recently, randomized data have demonstrated that prostate-directed therapy (PDT) is associated with an improvement in overall survival (OS) among patients with low-volume metastatic disease. Tumor genomics represents an additional dimension to define the clinical trajectory of patients with mCSPC., Objective: To evaluate a high-risk (HiRi) genomic signature to predict the benefit from PDT., Design, Setting, and Participants: We performed a single-institution retrospective review of men with synchronous low-volume mCSPC who underwent DNA panel sequencing of their tumor. Patients were classified according to the presence of HiRi mutation including pathogenic mutations in TP53, ATM, BRCA1, BRCA2, or Rb1., Outcome Measurements and Statistical Analysis: The primary endpoint was to determine the effect of PDT on OS in patients with and without a HiRi mutation. A survival analysis was performed with the Kaplan-Meier method compared with log-rank test and multivariable Cox regression. The interaction between HiRi mutation and PDT was evaluated., Results and Limitations: A total of 101 patients with synchronous low-volume CSPC were included with a median follow-up of 44 mo. Approximately half of patients were found to have a HiRi pathogenic mutation (49%). Patients with HiRi mutations demonstrated median OS of 73 versus 66.8 mo (p = 0.3) for no PDT versus PDT. Conversely, patients without a HiRi mutation demonstrated a significant improvement in OS of 60 versus 105.3 mo (p < 0.001) for no PDT versus PDT. The p value for interaction for OS between PDT and HiRi mutation was statistically significant (p < 0.001). Limitations include the retrospective nature of the study., Conclusions: Here, we have identified a HiRi genomic biomarker that appears predictive for the lack of benefit from PDT in men with synchronous low-volume mCSPC. Further work validating these results is warranted., Patient Summary: In this report, we evaluated a high-risk genomic biomarker to predict the benefit from prostate-directed therapy for men with synchronous low-volume metastatic castration-sensitive prostate cancer. We found that men without a high-risk mutation appear to experience a greater clinical benefit from prostate-directed therapy than those with a high-risk mutation., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate the association of tumor burden with the prognosis in real‐world patients with metastatic castration‐sensitive prostate cancer and to investigate the eligibility for upfront intensification therapy. Methods: We retrospectively evaluated 679 patients with metastatic castration‐sensitive prostate cancer who were initially treated with conventional androgen deprivation therapy between August 2001 and November 2018. The primary purpose was to investigate the eligibility for upfront intensification therapy based on the progression of metastatic castration‐resistant prostate cancer. The secondary purpose included the comparison of the metastatic castration‐resistant prostate cancer progression rate, metastatic castration‐resistant prostate cancer‐free survival and overall survival after castration‐resistance in CHAARTED low‐ or high‐volume disease patients. Results: The number of patients with metastatic castration‐resistant prostate cancer progression was 119 (52%) and 319 (71%) in the low‐ and high‐volume disease groups, respectively. The metastatic castration‐resistant prostate cancer progression rate (P < 0.001) and castration‐resistant prostate cancer‐free survival (P < 0.001) were significantly different between the low‐ and high‐volume disease groups, but no difference was found for overall survival after castration resistance (P = 0.363). Multivariate Cox regression analysis showed no significant association between tumor burden and overall survival after castration resistance (P = 0.522; hazard ratio 1.14). Conclusions: The progression rate in metastatic castration‐resistant prostate cancer patients with the low‐volume disease under conventional androgen deprivation therapy is approximately 50%. Upfront intensification therapy might be beneficial for approximately half of patients with low‐volume disease. A novel maker to predict the castration‐resistant status is required to select optimal patients for upfront intensification therapy. [ABSTRACT FROM AUTHOR]

Background: Testosterone suppression is the standard treatment for advanced prostate cancer, and it is associated with side-effects that impair patients' quality of life, like sexual dysfunction, osteoporosis, weight gain, and increased cardiovascular risk. We hypothesized that abiraterone acetate with prednisone (AAP) and apalutamide, alone or in combination, can be an effective hormonal therapy also possibly decreasing castration-associated side effects.Methods: Phase II, open-label, randomized, efficacy trial of abiraterone acetate plus prednisone (AAP) and Androgen Deprivation Therapy (ADT) versus apalutamide versus the combination of AAP (without ADT) and apalutamide. Key eligibility criteria are confirmed prostate adenocarcinoma; biochemical relapse after definitive treatment (PSA ≥ 4 ng/ml and doubling time less than 10 months, or PSA ≥ 20 ng/ml); newly diagnosed locally advanced or metastatic prostate cancer; asymptomatic to moderately symptomatic regarding bone symptoms. Patients with other histology besides adenocarcinoma or previous use of hormonal therapy or chemotherapy were excluded.Discussion: There is an urgent need to study and validate regimens such as new hormonal agents that may add benefit to castration with an acceptable safety profile. We aim to evaluate if apalutamide in monotherapy or in combination with AAP is an effective and safety hormonal treatment that can spare patients of androgen deprivation therapy.Trial Registration: This trial was registered in ClinicalTrials.gov on October 16, 2017, under Identifier: NCT02867020. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the value of 68Ga-HBED-CC PSMA (68Ga-PSMA) PET/CT for response assessment in metastatic castration-sensitive and castration-resistant prostate cancer (mCSPC and mCRPC) during docetaxel chemotherapy.Methods: 68Ga-PSMA PET/CT was performed in seven mCSPC patients before and after six cycles of upfront docetaxel chemotherapy and in 16 mCRPC patients before and after three cycles of palliative docetaxel chemotherapy. Radiographic treatment response was evaluated separately on the 68Ga-PSMA PET and CT datasets. Changes in 68Ga-PSMA uptake (SUVmean) were assessed on a per-patient and a per-lesion basis using the PERCIST scoring system with slight modification. Treatment response was defined as absence of any PSMA uptake in all target lesions on posttreatment PET (complete response, CR) or a decrease in summed SUVmean of ≥30% (partial response, PR). The appearance of a new PET-positive lesion or an increase in summed SUVmean of ≥30% (progressive disease, PD) indicated nonresponse. A moderate change in summed SUVmean (between −30% and +30%) without a change in the number of target lesions was defined as stable disease (SD). For treatment response assessment on CT, RECIST1.1 criteria were used. Radiographic responses on 68Ga-PSMA PET [RR(PET)] and on CT [RR(CT)] were compared and correlated with biochemical response (BR). A decrease in serum PSA level of ≥50% was defined as biochemical PR.Results: Biochemical PR was found in six of seven patients with mCSPC (86%, 95% confidence interval 42% to 99.6%). The concordance rate was higher between BR and RR(PET) than between BR and RR(CT) (6/7 vs. 3/6 patients. 68Ga-PSMA PET and CT were concordant in only three patients (50%, 12% to 88%). In mCRPC patients, biochemical PR was found in six of 16 patients (38%, 15% to 65%). Outcome prediction was concordant between BR and RR(PET) in nine of 16 patients (56%), and between BR and RR(CT) in only four of 12 patients (33%) with target lesions on CT. 68Ga-PSMA PET and CT results corresponded in seven of 12 patients (58%, 28% to 85%).Conclusion: Our preliminary results suggest that 68Ga-PSMA PET might be a promising method for treatment response assessment in mCSPC and mCRPC. The data indicate that for different metastatic sites, the performance of 68Ga-PSMA PET in response assessment might be superior to that of the conventional CT approach and could help differentiate between progressive disease and treatment response. Because of the limited number of patients, the differences revealed in our study were not statistically significant. Thus larger and prospective studies are clearly needed and warranted to confirm the value of 68Ga-PSMA PET as an imaging biomarker for response assessment. [ABSTRACT FROM AUTHOR]

Abiraterone acetate, which targets enzymatic complexes playing a central role in steroidogenesis, demonstrated to increase survival significantly in both chemo-naive and docetaxel pretreated, becoming one of the drugs of choice for metastatic castration-resistant prostate cancer. More recently, this agent in combination to androgen deprivation therapy demonstrated to be efficacious also in metastatic castration-sensitive prostate cancer. The present review is aimed to outline the clinical development of abiraterone acetate, the pivotal trials which led to its approval for the clinical practice, new evidence about its efficacy in metastatic castration-sensitive prostate cancer, its place in the therapeutic landscape of prostate cancer and future directions of development. [ABSTRACT FROM AUTHOR]

The prognosis of men with metastatic, castration-sensitive prostate cancer (CSPC) depends on both the distribution and extent of metastases, among other things. Patients with low-volume or oligometastatic disease have improved survival compared with those with high-volume metastases. While chemohormonal therapy is the new standard of care for men with high-volume metastatic CSPC, stereotactic ablative radiotherapy (SABR) is emerging as a promising treatment option with low toxicity for the management of oligometastatic CSPC. Our review summarizes the current evidence on the role of SABR in oligometastatic prostate cancer. SABR shows control rates of metastases ranging from 88% to 100% at 6 months to 3 years, and progression-free survival commonly reported as >50% for the first 12 months. In addition, SABR may allow androgen-deprivation therapy to be delayed by more than 2 years in selected patients, minimizing the chronic side effects associated with such therapy. However, much still needs to be learned before SABR can be implemented as standard treatment for oligometastatic prostate cancer. [ABSTRACT FROM AUTHOR]