Impact of Race on Outcomes of High-Risk Patients With Prostate Cancer Treated With Moderately Hypofractionated Radiotherapy in an Equal Access Setting
Background: Moderately hypofractionated radiotherapy (MHRT) is an accepted treatment for localized prostate cancer; however, limited MHRT data address high-risk prostate cancer (HRPC) and/or African American patients. We report clinical outcomes and toxicity profiles for individuals with HRPC treated in an equal access system.
Methods: We identified patients with HRPC treated with MHRT at a US Department of Veterans Affairs referral center. Exclusion criteria included < 12 months follow-up and elective nodal irradiation. MHRT included 70 Gy over 28 fractions or 60 Gy over 20 fractions. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicities were graded using Common Terminology Criteria for Adverse Events, version 5.0. Clinical endpoints, including biochemical recurrence-free survival (BRFS), distant metastases-free survival (DMFS), overall survival (OS), and prostate cancer – specific survival (PCSS) were estimated using Kaplan-Meier methods. Clinical outcomes, acute toxicity, and late toxicity-free survival were compared between African American and White patients with logistic regression and log-rank testing.
Results: Between November 2008 and August 2018, 143 patients with HRPC were treated with MHRT and followed for a median of 38.5 months; 82 (57%) were African American and 61 were White patients. Concurrent androgen deprivation therapy (ADT) was provided for 138 (97%) patients for a median duration of 24 months. No significant differences between African American and White patients were observed for 5-year OS (73% [95% CI, 58%-83%] vs 77% [95% CI, 60%-97%]; P = .55), PCSS (90% [95% CI, 79%-95%] vs 87% [95 % CI, 70%-95%]; P = .57), DMFS (91% [95% CI, 80%-96%] vs 81% [95% CI, 62%-91%]; P = .55), or BRFS (83% [95% CI, 70%-91%] vs 71% [95% CI, 53%-82%]; P = .57), respectively. Rates of acute grade 3+ GU and GI were low overall (4% and 1%, respectively). Late toxicities were similarly favorable with no significant differences by race.
Conclusions: Individuals with HRPC treated with MHRT in an equal access setting demonstrated favorable clinical outcomes that did not differ by race, alongside acceptable rates of acute and late toxicities.
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
