Interim report of image-guided conformal high-dose-rate brachytherapy for patients with unfavorable prostate cancer: The William Beaumont Phase II dose-escalating trial

Purpose: We analyzed our institution's experience treating patients with un favorable prostate cancer in a prospective Phase II dose-escalating trial o f external beam radiation therapy (EBRT) integrated with conformal high-dos e-rate (HDR) brachytherapy boosts. This interim report discusses treatment outcome and prognostic factors using this treatment approach. Methods and Materials: From November 1991 through February 1998, 142 patien ts with unfavorable prostate cancer were prospectively treated in a dose-es calating trial with pelvic EBRT in combination with outpatient HDR brachyth erapy at William Beaumont Hospital. Patients with any of the following char acteristics were eligible: pretreatment prostate-specific antigen (PSA) gre ater than or equal to 10.0 ng/ml, Gleason score greater than or equal to 7, or clinical stage T2b or higher. All patients received pelvic EBRT to a me dian total dose of 46.0 Gy. Pelvic EBRT was integrated with ultrasound-guid ed transperineal conformal interstitial iridium-192 HDR implants. From 1991 to 1995, 58 patients underwent three conformal interstitial HDR implants d uring the first, second, and third weeks of pelvic EBRT. After October 1995 , 84 patients received two interstitial implants during the first and third weeks of pelvic EBRT. The dose delivered via interstitial brachytherapy wa s escalated from 5.50 Gy to 6.50 Gy for each implant in those patients rece iving three implants, and subsequently, from 8.25 Gy to 9.50 Gy per fractio n in those patients receiving two implants. To improve implant quality and reduce operator dependency, an on-line, image-guided interactive dose optim ization program was utilized during each HDR implant. No patient received h ormonal therapy unless treatment failure was documented. The median follow- up was 2.1 years (range: 0.2-7.2 years). Biochemical failure was defined ac cording to the American Society for Therapeutic Radiology and Oncology Cons ensus Panel definition. Results: The pretreatment PSA level was greater than or equal to 10.0 ng/ml in 51% of patients. The biopsy Gleason score was greater than or equal to 7 in 58% of cases, and 75% of cases were clinical stage T2b or higher. Desp ite the high frequency of these poor prognostic factors, the actuarial bioc hemical control rate was 89% at 2 years and 63% at 5 years. On multivariate analysis, a higher pretreatment PSA level, higher Gleason score, higher PS A nadir level, and shorter time to nadir were associated with biochemical f ailure. In the entire population, 14 patients (10%) experienced clinical fa ilure at a median interval of 1.7 years (range: 0.2-4.5 years) after comple ting RT. The 5-year actuarial clinical failure rate was 22%. The 5-year act uarial rates of local failure and distant metastasis were 16% and 14%, resp ectively. For all patients, the 5-year disease-free survival, overall survi val, and cause-specific survival rates were 89%, 95%, and 96%, respectively . The 5-year actuarial rate of RTOG Grade 3 late complications was 9% with no patient experiencing Grade 4 or 5 acute or late toxicity. Conclusion: Pelvic FBRT in combination with image-guided conformal HDR brac hytherapy boosts appears to be an effective treatment for patients with unf avorable prostate cancer with minimal associated morbidity. Our dose-escala ting trial will continue. (C) 2000 Elsevier Science Inc.