Impact of obesity on outcomes after definitive dose‐escalated intensity‐modulated radiotherapy for localized prostate cancer

Abstract

INTRODUCTION Previous publications have shown conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy prior to the dose escalation era. Our goal is to determine whether increasing BMI is associated with CaP outcomes in men with localized CaP treated with dose escalated radiotherapy. METHODS We identified patients with localized (T1b-T4N0M0) CaP treated with definitive intensity modulated radiation therapy (IMRT) and image guidance (IGRT) from 2001–2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI category and the risk of biochemical failure (BF), distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). RESULTS Of the 1,442 patients identified, there were 20% with BMI<25 kg/m2, 48% with BMI 25–29.9 kg/m2, 23% with BMI 30–34.9 kg/m2, 6% with 35–39.9 kg/m2, and 4% with BMI≥40 kg/m2. Median follow-up was 47.6 months (range 1–145) with median age of 68 years (range 36–89). Median dose was 78Gy (range 76–80) and 30% of patients received androgen deprivation therapy. Increasing BMI was inversely associated with age (p<0.001) and pre-treatment PSA (p=0.018). On multivariable analysis, increasing BMI was associated with increased risk of BF (HR=1.03[95% CI 1.00–1.07], p=0.042), DM (HR=1.07[1.02–1.11], p=0.004), CSM (HR=1.15[1.07–1.23], p<0.001), and OM (HR=1.05[1.02–1.08], p=0.004). CONCLUSION For CaP patients receiving dose-escalated IMRT with IGRT, increasing BMI appears to be associated with an increased risk of biochemical failure, distant metastases development, cause-specific and overall survival.

Obesity and cancer treatment efficacy: Existing challenges and opportunities

“…Radiation therapy uses targeted ionizing radiation to destroy tumor cells. Among patients with prostate cancer, multiple studies of external‐beam radiation therapy have reported an association between obesity and inferior outcomes . Proposed mechanisms for this correlation include technical issues of delivering radiation therapy to obese patients, such as difficulty with daily set up and an increased likelihood of shifts in tumor location among obese patients .…”

“…Among patients with prostate cancer, multiple studies of external-beam radiation therapy have reported an association between obesity and inferior outcomes. 16 Proposed mechanisms for this correlation include technical issues of delivering radiation therapy to obese patients, such as difficulty with daily set up and an increased likelihood of shifts in tumor location among obese patients. 17 It has been reported that obese patients with cervical cancer also experience increased treatment-related toxicities compared with normal weight patients.…”

ACR Appropriateness Criteria ® external beam radiation therapy treatment planning for clinically localized prostate cancer, part I of II

“…Obese patients tend to have larger interfractional shifts because of setup errors,142, 143 and anatomic variations in obese patients may lead to significant variations in delivered dose 144 . Obese patients also have been reported to have higher rates of prostate cancer recurrence after EBRT 145, 146. There is no direct evidence regarding the effectiveness of specific immobilization or IGRT techniques in obese patients.…”

The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance

“…Concerning the impact of AT on sensitivity to radiotherapy, the results remain controversial since some studies have shown an adverse effect of obesity on clinical outcome of prostate cancer patients [ 171 – 173 ], while other reports have indicated no difference in efficacy between obese and lean patients in prostate and esophageal cancers [ 174 – 176 ]. By contrast, the link between obesity and resistance seems to be more firmly established for chemotherapy and endocrine therapy.…”