Patient-reported Outcomes and Late Toxicity After Postprostatectomy Intensity-modulated Radiation Therapy

Abstract

Background: Limited long-term data characterize patient-reported quality of life (QOL) following postprostatectomy intensity-modulated radiation therapy (PPRT), and predictors of decline are poorly defined.

Objective: To identify modifiable dosimetric and clinical risk factors impacting QOL and late toxicity following PPRT.

Design, setting, and participants: A prospective cohort study of consecutive men with prostate cancer who received PPRT between 2007 and 2015 at a single academic institution.

Intervention: Patients were prospectively evaluated using the Expanded Prostate Cancer Index Composite (EPIC-26) QOL instrument. Radiation Therapy Oncology Group/Common Toxicity Criteria for Adverse Events toxicity grades were assigned at every follow-up visit. Treatment was delivered to the prostate bed (median 68Gy)±pelvic lymphatics (65%, median 50.4Gy) with daily image guidance. Androgen deprivation therapy was concomitantly administered to 132 (66%) men for a median of 4mo.

Outcome measurements and statistical analysis: Changes were deemed relevant if they exceeded the minimally clinically important difference (MCID), as calculated by a distribution-based method. Generalized estimating equation models and Cox regression were used for QOL and late toxicity univariate and multivariable analysis.

Results and limitations: Overall, 199 men were identified with a median follow-up of 33mo. Overall urinary function (UF), bowel function (BF), sexual function (SF), and urinary irritation/obstruction (UI/UO) scores were never lower than the MCID. Between 8% and 18% of men experienced a small multidomain (1× MCID) decline, and 0-8% experienced a moderate multidomain decline (2× MCID) at a given time point up to 84mo after PPRT. The rates of freedom from grade 2 or higher (Gr2+) genitourinary (GU) and gastrointestinal (GI) toxicity were 94% and 95%, respectively, at 4yr. Factors associated with worse QOL or toxicity included longer time to PPRT (UC and UF), higher BMI (UF, BF, and late GI toxicity), older age (BF, SF, and late GU toxicity); hormone therapy (SF), total dose (late GI toxicity), tobacco history (BF), and higher bladder V70Gy (UC, UF, and late GU toxicity).

Conclusions: Long-term QOL and late toxicity are favorable following postprostatectomy radiation therapy. Identifiable clinical and dosimetric risk factors may guide decision making to optimize urinary, sexual, and bowel function.

Patient summary: The following study provides a detailed report of favorable patient-reported quality of life and late side-effect profiles of radiation therapy following surgery for localized prostate cancer. Our findings provide patients guidance on what symptoms to expect if they are planning to undergo radiation therapy in this setting. It also allows physicians to counsel patients appropriately, and modify certain clinical and radiation-related risk factors to optimize quality of life.

Keywords: Adjuvant or salvage; Intensity-modulated radiation therapy; Late toxicity; Long term; Patient-reported outcomes; Postoperative; Postprostatectomy; Prostate cancer; Quality of life; Radiation therapy.