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


METHODS
Patients 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.


RESULTS
From 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.


CONCLUSIONS
Compared 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.
Department of Radiation Oncology, University of Michigan Hospital, Ann Arbor, MI, USA. jvainsh@med.umich.edu
Jeffrey
J
Vainshtein
Eyad
E
Abu-Isa
Karin B
KB
Olson
Michael E
ME
Ray
Howard M
HM
Sandler
Dan
D
Normolle
Dale W
DW
Litzenberg
Kathryn
K
Masi
Charlie
C
Pan
Daniel A
DA
Hamstra
D000230:Adenocarcinoma / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011788:Quality of Life; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D014521:Urethra / Q000528:radiation effects*