Treatment Intensification for Low-risk Metastatic Hormone-sensitive Prostate Cancer: The Time Is Now.
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ABSTRACT:
SUBMITTER: McKay RR
PROVIDER: S-EPMC9525807 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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Treatment Intensification for Low-risk Metastatic Hormone-sensitive Prostate Cancer: The Time Is Now.
European urology open science 20220928
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Project description:BackgroundIn metastatic hormone-sensitive prostate cancer (mHSPC), androgen deprivation therapy and standard of care treatment intensification with docetaxel and/or an androgen receptor signaling inhibitor (ARSI) are associated with improved survival outcomes for appropriate patients.MethodsThis retrospective study selected patients with de novo mHSPC diagnosed between 2014 and 2023 from CancerLinQ Discovery®, a United States (US)-based, de-identified clinical database. Patient-level data, including clinical characteristics, treatments, and demographics, were collected from CancerLinQ. Treatment intensification was defined as the use of docetaxel, abiraterone, apalutamide, enzalutamide, or docetaxel plus abiraterone or darolutamide. Patient characteristics and treatment intensification data were analyzed descriptively and using multivariable logistic regression.ResultsOf the 3,684 patients with mHSPC, the overall rate of treatment intensification was 58.4% but increased from 32.5% in 2014 to 67.5% in 2023. A relative decline in docetaxel use was accompanied by an increase in ARSI use. Black patients with mHSPC were less likely to receive treatment identification (OR 0.78, 95% CI 0.64-0.95, P = 0.013). Treatment intensification was also less likely for patients of older age and increased ECOG performance status. Despite increasing treatment intensification for Black patients with mHSPC over time, rates of docetaxel use are disproportionately declining relative to White patients.ConclusionsTreatment intensification rates are increasing to include the majority of patients with mHSPC. However, treatment disparities exist for Black patients, who are less likely to receive intensification. These findings illustrate the importance of promoting treatment intensification in appropriate patients and addressing racial treatment disparities.
| S-EPMC11573622 | biostudies-literature
Project description:BackgroundThe treatment strategy for metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly in recent years. Based on various guidelines, an upfront androgen receptor signaling inhibitor (ARSI) is the first choice, but in patients of Asian descent, including Japanese patients, there are a certain number of cases in which androgen deprivation therapy (ADT) and CAB are more effective. If patients can be identified who show a marked response to ADT within 12 weeks after the initiation of ADT, which is the inclusion criterion for ARSI clinical trials targeting mCSPC, it would be valuable from an economic standpoint.MethodsA total of 218 patients with pure prostate adenocarcinoma and treated with ADT at the Kanazawa University Hospital between January 2000 and December 2020 were included in this study. As a risk classification for mCSPC, in addition to the LATITUDE and CHAARTED criteria, we used the castration-sensitive prostate cancer classification proposed by Kanazawa University (Canazawa), developed by the Department of Urology of Kanazawa University. The Canazawa classification was based on three factors: Gleason pattern 5, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) ≥ 300 IU/L. It defined patients with one factor or less as low-risk and patients with two or three factors as high-risk. The overall survival (OS) and time to castration resistance (TTCR) were estimated retrospectively using the Kaplan-Meier method, and factors associated with TTCR were identified using univariate and multivariate analyses.ResultsThe median follow-up period was 40.4 months, the median OS period was 85.2 months, and the median TTCR period was 16.4 months. The Canazawa risk classification provided the clearest distinction between the OS and TTCR in mCSPC patients. Multivariate analysis revealed a decrease in PSA levels of <95% at 12 weeks after ADT initiation and was a predictor of short TTCR in low-risk, low-volume patients across all risk classifications.ConclusionThe Canazawa classification differentiated the prognosis of mCSPC patients more clearly. A PSA reduction rate of <95% at 12 w after starting ADT in low-risk, low-volume patients of all risk classifications was significantly shorter than the TTCR. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs based on the rate of PSA reduction at 12 w.
| S-EPMC11430633 | biostudies-literature
Project description:ObjectiveTo conduct a systematic literature review of real-world data (RWD) studies to summarise treatment patterns among men with metastatic hormone-sensitive prostate cancer (mHSPC). While androgen-deprivation therapy (ADT) is a primary treatment strategy for mHSPC, ADT intensification with androgen receptor pathway inhibitors (ARPIs) and/or chemotherapy is recommended by current guidelines and has improved clinical outcomes in the last decade.MethodsWe searched electronic databases (PubMed; Excerpta Medica dataBASE [EMBASE]) for eligible studies (retrospective or prospective observational RWD studies examining mHSPC treatment patterns) between database inception and July 2023, and manually screened the past 2 years of relevant conference proceedings.ResultsOf 2336 retrieved citations, 29 studies met the inclusion criteria, covering North America (United States, n = 21; Canada, n = 2), Europe (n = 8), and Asia (n = 6). Most studies utilised retrospective cohorts (n = 26) and included men with a median age of ≥70 years (n = 20). ADT monotherapy was predominantly used across geographies, followed by ADT + ARPI and ADT + docetaxel in the United States and Europe but not in Asia, where use of each combination remained low. Studies with recent electronic medical record data from cancer centres/registries showed >40% use of ADT + ARPI in the United States and Europe. Abiraterone was the most frequently used ARPI, followed by enzalutamide. Quantitative factors associated with ADT intensification were high disease burden, younger age, Eastern Cooperative Oncology Group performance status score of 0 to 1, fewer comorbidities, and oncologist physician specialty; qualitative factors were patient preference, unsatisfactory response to ADT, ability to tolerate adverse events, and absence of cost barriers.ConclusionWhile there was an increasing trend in ADT intensification for mHSPC over the study period across geographies, use remained suboptimal considering the high proportion of patients who were still receiving ADT monotherapy only. These findings highlight the need for interventions to further optimise current mHSPC therapies with high guideline concordance.
| S-EPMC11842892 | biostudies-literature
Project description:The treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has dramatically evolved. Monotherapy androgen deprivation therapy (ADT) with testosterone suppression alone is no longer the standard of care as multiple global phase 3 trials of different combinatorial strategies have been clinically and statistically successful and the combinations have been incorporated into guidelines on advanced prostate cancer. For appropriate patients, clinicians should consider combining ADT with docetaxel or an androgen receptor pathway inhibitor, or possibly with both. Shared patient-physician decision-making mandates a review of the level 1 evidence supporting the optimization and intensification of combination therapy for patients with mHSPC. Here we discuss the evidence underscoring intensification strategies as the standard of care for low-volume, low-risk mHSPC.Patient summaryWe discuss treatment strategies for men with metastatic prostate cancer. Combinations of androgen deprivation therapy (ADT) and drugs that inhibit the androgen receptor pathway are superior to ADT alone and prolong survival in patients with metastatic hormone-sensitive prostate cancer.
| S-EPMC9523347 | biostudies-literature
Project description:BackgroundCurrently, metastatic hormone-sensitive prostate cancer (mHSPC) patients are often treated with docetaxel chemotherapy at the initiation of hormonal therapy. This treatment is based on the results of two pivotal trials. However, trial populations are not a representative of real-world patient populations.ObjectiveWe aimed to analyze whether survival rates in our daily practice cohort is comparable with those in clinical trials and to characterize the tolerability of docetaxel chemotherapy in daily practice.Design setting and participantsIn this retrospective cohort analysis, we studied 159 mHSPC patients treated with early docetaxel from April 2014 up to June 2020 in a top clinical hospital in The Netherlands. Patients were selected using hospital pharmacy records.Outcome measurements and statistical analysisWe compared the results of our cohort with the results of the cohorts of the two pivotal trials. We aimed to analyze the survival rates in our cohort and characterize the tolerability of docetaxel chemotherapy in daily practice.Results and limitationsDespite the relatively high number of comorbidities in our daily practice cohort, overall survival of our cohort showed great similarity with that of the two pivotal trials: 60.2 mo compared with 57.6 and 59.1 mo. Furthermore, early docetaxel was well tolerated in daily practice. Nearly 90% of the patients completed the full six cycles, and polyneuropathy led to relatively few dose reductions (6.9%).ConclusionsEarly docetaxel is well tolerated in daily practice. Our daily practice cohort showed great similarity in overall survival to the clinical trials. Our results might be of interest in the developing landscape of mHSPC treatment.Patient summaryWe studied docetaxel chemotherapy for metastatic prostate cancer in daily practice. These patients have the same survival as selected patients participating in clinical trials. Docetaxel was well tolerated in daily practice.
| S-EPMC8546919 | biostudies-literature
Project description:The landscape of advanced prostate cancer treatment has evolved tremendously in past decades. The treatment paradigm has shifted from androgen deprivation therapy (ADT) alone to doublet combinations comprising ADT with docetaxel or an androgen receptor inhibitor, and now triplet therapy involving all 3 classes of agents. Robust clinical data has demonstrated survival benefits with this strategy of upfront treatment intensification. Subgroup analysis has alluded to the importance of tailoring treatment according to metastatic disease burden. However, defining the volume of disease is becoming increasingly controversial due to the advent of next generation molecular imaging. Several trials testing established agents in the castrate-resistant setting are now underway in metastatic hormone sensitive prostate cancer patients. As the treatment milieu is enriched earlier in the disease trajectory, future studies should elucidate biomarkers to further define specific patient populations who will benefit most from treatment intensification and/or de-escalation, with what agents and for what duration.
| S-EPMC10415497 | biostudies-literature
Project description:IntroductionTreatment intensification beyond androgen deprivation therapy (ADT) has shown survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC). There is a need to better understand how these novel treatments fit in real-world practice.MethodsUsing electronic medical records and administrative data, a population-based, retrospective cohort study of patients diagnosed with de novo mCSPC between 2010 and 2020 in Alberta, Canada, and initiated on ADT was conducted. Treatment intensification was defined as the receipt of apalutamide, abiraterone acetate, enzalutamide, or chemotherapy (e.g., docetaxel) within 180 days of ADT initiation.ResultsA total of 2515 de novo mCSPC were identified, with 2098 (83%) patients initiating ADT post-diagnosis. Of those, 525 (25%) received intensification beyond ADT. Three percent of patients were intensified in 2010-2013; this increased to 67% in 2020. From 2014-2017, docetaxel was the most used approach, although it was supplanted by abiraterone acetate, apalutamide, and enzalutamide from 2018 onwards. In multivariable logistic regression analyses of patients diagnosed from 2014-2020, significant predictors of intensification were younger age at diagnosis, lower Charlson comorbidity index, greater number of metastatic sites, shorter time to ADT initiation, referral to a medical oncologist, transurethral resection of the prostate or radiation prior to ADT, and more recent year of diagnosis (all p<0.05).ConclusionsThere has been a considerable increase in the use of ADT intensification therapies that correspond with the timing of clinical trial data and approvals of novel agents.
| S-EPMC11790044 | biostudies-literature
Project description:The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.
| S-EPMC8409413 | biostudies-literature
Project description:PurposeTo capture UK societal health utility values for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and the disutility associated with treatment-related adverse events (AEs) to inform future cost-utility analyses.MethodsA literature review, and patient and clinical expert interviews informed the development of health states characterising mHSPC symptoms and the impact of treatment-related AEs on health-related quality of life (HRQL). Three base health states were developed describing a typical patient with high-risk mHSPC: receiving androgen deprivation therapy (ADT) [Base State 1]; receiving docetaxel plus ADT [Base State 2]; completed docetaxel and still receiving ADT whose disease has not yet progressed [Base State 3]. Six additional health states described treatment-related AEs. The health states were validated with experts and piloted with general public participants. Health state utilities were obtained using the time trade-off (TTO) method with 200 members of the UK general population. A generalised estimating equation (GEE) model was used to estimate disutility weights.ResultsMean TTO scores for Base State 1 to 3 were 0.71 (SD = 0.26), 0.64 (SD = 0.27), and 0.68 (SD = 0.26), respectively, indicating that receiving docetaxel plus ADT was most impactful on HRQL. The GEE model indicated when compared to Base State 2 that the nausea and vomiting AE had the most impact on HRQL (- 0.21), while alopecia was least burdensome (- 0.04).ConclusionsThe study highlights the differences in utility between base health states and the significant impact of treatment-related AEs on the HRQL of patients with mHSPC. These findings underline the importance of accounting for impaired HRQL when assessing treatments for mHSPC.
| S-EPMC6470112 | biostudies-literature
Project description:BackgroundAndrogen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone.MethodsWe assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone.ResultsA total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%.ConclusionsSix cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.).
| S-EPMC4562797 | biostudies-literature