David J. Carpenter, MDa; Divya Natesan, MDa; R. Warren Floyda; Taofik Oyekunle, MSa,b; Donna Niedzwiecki, PhDa; Laura Watersb; Devon Godfrey, PhDa,b; Michael J. Moravan, MDc; Rhonda L. Bitting, MDb,d; Jeffrey R. Gingrich, MDb,d; W. Robert Lee, MDa; and Joseph K. Salama, MDa,b Correspondence: David Carpenter (david.j.carpenter@duke.edu)
aDuke University School of Medicine, Durham, North Carolina bDurham Veterans Affairs Health Care System, North Carolina cSt. Louis Veterans Affairs Health Care System, Missouri dDuke Cancer Institute, Center for Prostate & Urologic Cancers, Duke University, Durham, North Carolina
Author disclosures
The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.
Ethics
The US Department of Veterans Affairs (VA) places legal restrictions on access to veteran’s health care data, which includes both identifying data and sensitive patient information. The analytic data sets used for this study are not permitted to leave the VA firewall without a data use agreement. This limitation is consistent with other studies based on VA data. However, VA data are made freely available to researchers behind the VA firewall with an approved VA study protocol. For more information, please visit https://www.virec.research.va.gov or contact the VA Information Resource Center (VIReC) at vog.av@CeRIV.
Despite widespread acceptance in prostate cancer radiotherapy guidelines, routine use of MHRT seems limited across all stages of localized prostate cancer.1,2 Late toxicity is a frequently noted concern regarding MHRT use. Higher rates of late grade 2+ GI toxicity were observed in the hypofractionation arm of the HYPRO trial.17 While RTOG 0415 did not include patients with HRPC, significantly higher rates of physician-reported (but not patient-reported) late grade 2+ GI and GU toxicity were observed using the same MHRT fractionation regimen used for the majority of individuals in our cohort.9 In our study, the steady increase in late grade 2 GU toxicity is consistent with what is seen following conventionally fractionated radiotherapy and is likely multifactorial.38 The mean IPSS difference of 2/35 from pre-MHRT baseline to the time of last follow-up suggests minimal quality of life decline. The relatively stable IPSSs over time alongside the > 50% prevalence of late grade 2 GU toxicity per CTCAE grading seems consistent with the discrepancy noted in RTOG 0415 between increased physician-reported late toxicity and favorable patient-reported quality of life scores.9 Moreover, significant variance exists in toxicity grading across scoring systems, revised editions of CTCAE, and physician-specific toxicity classification, particularly with regard to the use of adrenergic receptor blocker medications. In light of these factors, the high rate of late grade 2 GU toxicity in our study should be interpreted in the context of largely stable post-MHRT IPSSs and favorable rates of late GI grade 2+ and late GU grade 3+ toxicity.
Limitations
This study has several inherent limitations. While the size of the current HRPC cohort is notably larger than similar populations within the majority of phase 3 MHRT trials, these data derive from a single VA hospital. It is unclear whether these outcomes would be representative in a similar high-risk population receiving care outside of the VA equal access system. Follow-up data beyond 5 years was available for less than half of patients, partially due to nonprostate cancer–related mortality at a higher rate than observed in HRPC trial populations.12,15,16 Furthermore, all GI toxicity events were exclusively physician reported, and GU toxicity reporting was limited in the off-trial setting with not all patients routinely completing IPSS questionnaires following MHRT completion. However, all patients were treated similarly, and radiation quality was verified over the treatment period with mandated accreditation, frequent standardized output checks, and systematic treatment review.39
Conclusions
Patients with HRPC treated with MHRT in an equal access, off-trial setting demonstrated favorable rates of biochemical control with acceptable rates of acute and late GI and GU toxicities. Clinical outcomes, including biochemical control, were not significantly different between African American and White patients, which may reflect equal access to care within the VA irrespective of income and insurance status. Incorporating VA services, such as access to primary care, mental health services, and transportation across other health care systems may aid in characterizing and mitigating racial and gender disparities in oncologic care.
Acknowledgments
Portions of this work were presented at the November 2020 ASTRO conference. 40
