Abstract
BackgroundLow-risk prostate cancer (PCa) patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life. Acute urinary symptoms are common during external beam radiotherapy (EBRT), while chronic symptoms have been linked to urethral dose. Since most low-risk PCa occurs in the peripheral zone (PZ), we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy (US-IMRT) could improve urinary health-related quality of life (HRQOL) while maintaining high rates of PCa control.MethodsPatients with National Comprehensive Cancer Network (NCCN) defined low-risk PCa with no visible lesion within 5 mm of the prostatic urethra on MRI were randomized to US-IMRT or standard (S-) IMRT. Prescription dose was 75.6 Gy in 41 fractions to the PZ + 3–5 mm for US-IMRT and to the prostate + 3 mm for S-IMRT. For US-IMRT, mean proximal and distal urethral doses were limited to 65 Gy and 74 Gy, respectively. HRQOL was assessed using the Expanded Prostate Cancer Index (EPIC) Quality of Life questionnaire. The primary endpoint was change in urinary HRQOL at 3 months.ResultsFrom June 2004 to November 2006, 16 patients were randomized, after which a futility analysis concluded that continued accrual was unlikely to demonstrate a difference in the primary endpoint. Mean change in EPIC urinary HRQOL at 3 months was −0.5 ± 11.2 in the US-IMRT arm and +3.9 ± 15.3 in the S-IMRT arm (p = 0.52). Median PSA nadir was higher in the US-IMRT arm (1.46 vs. 0.78, p = 0.05). At 4.7 years median follow-up, three US-IMRT and no S-IMRT patients experienced PSA failure (p = 0.06; HR 8.8, 95% CI 0.9–86). Two out of 3 patients with PSA failure had biopsy-proven local failure, both located contralateral to the original site of disease.ConclusionsCompared with S-IMRT, US-IMRT failed to improve urinary HRQOL and resulted in higher PSA nadir and inferior biochemical control. The high rate of PSA failure and contralateral local failures in US-IMRT patients, despite careful selection of MRI-screened low-risk patients, serve as a cautionary tale for focal PCa treatments.
Highlights
Low-risk prostate cancer (PCa) patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life
Due to slower than expected accrual, an unplanned futility analysis was conducted in January 2007, which determined that due to the slow accrual rate, lower than expected baseline urinary Expanded Prostate Index Composite (EPIC) scores, and smaller than expected changes in urinary EPIC score in both treatment arms, continued enrollment was unlikely to demonstrate a difference in the primary endpoint, and the data safety monitoring board recommended closure of the study
Baseline EPIC urinary scores were 86.9 ± 13.4 and 81.6 ± 16.5 in the US-intensity modulated radiation therapy (IMRT) and SIMRT arms, respectively, which was notably lower than the anticipated baseline score of 95
Summary
Low-risk prostate cancer (PCa) patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life. Since most low-risk PCa occurs in the peripheral zone (PZ), we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy (US-IMRT) could improve urinary health-related quality of life (HRQOL) while maintaining high rates of PCa control. In over 1500 patients treated at Memorial Sloan-Kettering Cancer Center, Zelefsky et al reported acute and late GU symptoms in 37% and 20% who received 81 Gy with intensity modulated radiation therapy (IMRT), compared with rates of 22% and 12% in those receiving lower doses with non-IMRT technique, respectively [5]. Dose-escalated EBRT has become standard of care based on multiple randomized trials demonstrating improvements in biochemical control [6,7,8,9]
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