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. 2024 Dec 2;7(12):e2448707.
doi: 10.1001/jamanetworkopen.2024.48707.

Physician Reasons for or Against Treatment Intensification in Patients With Metastatic Prostate Cancer

Neeraj Agarwal  1 , Daniel J George  2 , Zachary Klaassen  3 , Rickard Sandin  4 , Jake Butcher  5 , Amanda Ribbands  5 , Liane Gillespie-Akar  5 , Birol Emir  6 , David Russell  6 , Agnes Hong  6 , Krishnan Ramaswamy  6 , Stephen J Freedland  7   8
Affiliations

Physician Reasons for or Against Treatment Intensification in Patients With Metastatic Prostate Cancer

Neeraj Agarwal et al. JAMA Netw Open. .

Abstract

Importance: Clarifying the underutilization of treatment intensification (TI) for metastatic castration-sensitive prostate cancer (mCSPC) may improve implementation of evidence-based medicine and survival outcomes.

Objective: To investigate physicians' beliefs about TI in mCSPC to understand the gap between evidence-based guidelines and clinical practice.

Design, setting, and participants: This 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 measures: The 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).

Results: In 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 relevance: The 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Agarwal reported receiving honoraria before May 2021 and during his lifetime for consulting from Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics and receiving research funding (to the institution) from Arnivas, Astellas, AstraZeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, CRISPR Therapeutics, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. Dr George reported receiving personal fees from ABRX, AstraZeneca, AVEO, Bayer, Eisai, Exelixis, IdeOncology, Janssen, Merck, MJH Associates, Nektar, Pfizer, Propella TX, Sanofi, Seattle Genetics, Sumitovant Biopharma, Surface Oncology, UroGPO, UroToday, and WebMD and receiving grants from Astellas, AstraZeneca, BMS, CORVUS, Exelixis, Janssen Pharma, Novartis, Pfizer, and Surface Oncology outside the submitted work. Dr Klaassen reported receiving personal fees from Astellas/Pfizer, Bayer, and Novartis during the conduct of the study. Dr Sandin reported having stock options in Pfizer outside the submitted work. Mr Butcher and Mss Ribbands and Gillespie-Akar reported receiving fees from Pfizer for a subscription to the Prostate Cancer Wave IV Disease Specific Programme (DSP) during the conduct of the study and having a patent for the DSP licensed to Adelphi Real World (ARW). Dr Emir, Dr Russell, and Ms Hong reported having stock options in Pfizer outside the submitted work. Dr Ramaswamy reported having stock options in Pfizer and Johnson & Johnson outside the submitted work. Dr Freedland reported receiving personal fees from Pfizer and Astellas during the conduct of the study and receiving personal fees from Astellas, Bayer, Pfizer, Sanofi, Merck, AstraZeneca, Eli Lilly, Novartis, and Janssen outside the submitted work.

Figures

Figure 1.
Figure 1.. Most Frequently Cited Physician-Reported Reasons for First-Line Treatment Decisions
(A) Treatment intensification (TI) involved the addition of an androgen receptor pathway inhibitor (ARPI [enzalutamide, apalutamide, abiraterone, or darolutamide]), chemotherapy, or both to androgen deprivation therapy. Percentages have been calculated out of the respective TI status base. Physicians could give multiple responses. There were 617 total patients, of whom 187 (30.3%) received TI and 430 (69.7%) did not. Data are shown in eTable 3 in Supplement 1. (B) There were 207 patients treated by oncologists or urologists; 114 were treated by oncologists and 93 were treated by urologists. mCSPC indicates metastatic castration-sensitive prostate cancer; PSA, prostate-specific antigen; QOL, quality of life.
Figure 2.
Figure 2.. Multivariable Analysis of Physician-Reported Reasons and Patient Characteristics Associated With Likelihood of Treatment Intensification (TI)
The figure only shows physician-reported reasons associated with likelihood of TI. TI involved the addition of an androgen receptor pathway inhibitor (ARPI [enzalutamide, apalutamide, abiraterone, or darolutamide]) and/or chemotherapy to androgen deprivation therapy. Other physician-related factors, including physician specialty, practice setting, concerns about drug safety and tolerability, patient quality of life, and insurance reimbursement or access, did not show associations with first-line TI. OR indicates odds ratio.
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Comment in

  • doi: 10.1001/jamanetworkopen.2024.48660

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