Randomized phase II trial of urethral sparing intensity modulated radiation therapy in low-risk prostate cancer: implications for focal therapy

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.

Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy

“…The date of treatment was also slightly different, such that IMRT and brachytherapy technique and outcomes had improved by the time the SBRT cohort was collected [25][26][27]. However, we note that IMRT was associated with an MCD only for bowel QOL in our multivariable model, and margin reduction through IGRT has been shown to minimize bowel QOL impact in other studies using the EPIC survey [26,27]. Therefore, modern IMRT is likely to cause few QOL MCDs at 2 years, as we found for SBRT.…”

Focal high-dose-rate brachytherapy: A dosimetric comparison of hemigland vs. conventional whole-gland treatment

“…Another study was a randomized Phase II trial using an intensity-modulated radiation therapy (IMRT) urethral sparing technique (42). Patients in the urethral sparing arm had a mean reduced dose of 36.2% and 9.6% to the proximal and distal urethra compared with standard IMRT plans.…”

Dysuria Following Stereotactic Body Radiation Therapy for Prostate Cancer

“…In addition, we have decreased the bladder neck dose by reducing the anterior/ superior PTV expansion to 3 mm. From our clinical experience, such modifications have reduced the incidence and severity of the late urinary symptom flare and patient reported dysuria without increasing the risk of biochemical failures (27).…”

“…Treatment DVH goals included a maximum dose of 37 Gy to <5 cc of the bladder and <50% of the membranous urethra. While the prostatic urethra dose was not limited, we found that, by restricting the prescription isodose line to ≥75%, we were able to reduce the prostatic urethra dose to 133% of the prescription dose (27,28). Target position was verified every 30-60 s during each treatment using paired, orthogonal x-ray images (29).…”