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Hormonal Intensification Should Start at the Low-risk Stage in Metastatic Prostate Cancer.

ABSTRACT: 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 summary

We 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.

SUBMITTER: Jazayeri SB

PROVIDER: S-EPMC9523347 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Hormonal Intensification Should Start at the Low-risk Stage in Metastatic Prostate Cancer.

Jazayeri Seyed Behzad SB Cooley Lauren Folgosa LF Srivastava Abhishek A Shore Neal N

European urology open science 20220928

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 AD ...[more]

PMID: 36186607

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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.

Project description:ImportanceClarifying the underutilization of treatment intensification (TI) for metastatic castration-sensitive prostate cancer (mCSPC) may improve implementation of evidence-based medicine and survival outcomes.ObjectiveTo investigate physicians' beliefs about TI in mCSPC to understand the gap between evidence-based guidelines and clinical practice.Design, setting, and participantsThis survey study analyzed data from the Adelphi Real World retrospective survey, which comprised physician surveys that were linked to medical record reviews of US adult patients treated for mCSPC between July 2018 and January 2022.Main outcomes and measuresThe survey included questions on physician and practice demographics. Physicians completed patient record forms, based on patient medical records with information including patient demographics, clinical characteristics, and patient management. Physicians recalled reasons for prescribing decisions using 48 precoded and open-text responses. Bivariate and multivariable analyses assessed the likelihood of their patients receiving first-line TI; the main outcome was the likelihood of their patients receiving TI using odds ratios (ORs).ResultsIn total, 617 male patients met the analysis criteria (mean [SD] age, 68.6 [8.1] years). Among these patients, 349 (56.6%) were Medicare beneficiaries. Overall, 430 (69.7%) did not receive first-line TI with androgen receptor pathway inhibitors and/or chemotherapy. The 107 US-based physicians' top reasons for treatment choice for their patients were tolerability concerns (TI: 121 [64.7%]; no TI: 252 [58.6%]; P = .18) and following guideline recommendations (TI: 115 [61.5%]; no TI: 230 [53.5%]; P = .08). In the bivariate analysis, physicians seeking to reduce prostate-specific antigen (PSA) by 75% to 100% were more likely to provide first-line TI compared with physicians who aimed to lower PSA by 0% to 49% (OR, 1.63 [95% CI, 1.04-2.56]; P = .03). In the multivariable analysis, patients whose physicians based treatment choice on guidelines were more likely to receive TI than patients whose physicians did not report this reason (OR, 3.46 [95% CI, 1.32-9.08]; P = .01).Conclusions and relevanceThe findings of this study, which analyzed data from a medical records-linked clinical practice survey, indicated low rates of first-line TI for mCSPC despite guideline recommendations. Barriers to TI included lack of knowledge about guidelines and published efficacy and safety data. Physicians with greater PSA reduction goals were more likely to use TI. Physician education on treatment guidelines and clinical trial data, while raising expectations for PSA response, may increase rates of first-line TI in mCSPC.

Dataset Information

Hormonal Intensification Should Start at the Low-risk Stage in Metastatic Prostate Cancer.

Patient summary

Publications

Hormonal Intensification Should Start at the Low-risk Stage in Metastatic Prostate Cancer.

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