Results of high dose rate afterloading brachytherapy boost to conventional external beam radiation therapy for initial and locally advanced prostate cancer

Abstract

Purpose: To evaluate the impact on biochemical control (bNED), acute and late gastro-intestinal (GI) and urological (GU) morbidity of initial and locally advanced prostate cancer treated with fractionated transrectal ultrasound-guided (TRUS) high dose rate after loading brachytherapy (HDR-B) as a boost to conventional external beam radiation therapy (EBRT).

Patients and methods: From March 1997 to February 2000 a total of 119 patients with any of the following characteristics were eligible for study entry: biopsy proven adenocarcinoma Gleason scored (GS), initial prostatic specific antigen (PSA) level dosage 1992 AJCC clinical stage T3a or less, and prostatic volume <60 cc. All patients had prior to HDR-B a course of EBRT 6 MV photons to a median dose of 45 Gy, in 1.8 Gy fractions, to the prostate and seminal vesicles only. HDR-B treatment planning and dosimetric calculations were generated with the Nucletron Planning System. Patients were grouped into two groups, according to their risk for biochemical failure: low-risk group without (LR) or with neoadjuvant total androgen deprivation (AD) prior to EBRT (LR+AD) and high-risk group without (HR) or with neoadjuvant AD (HR+AD), for bNED and dose-escalation protocol. LR encompassed patients who presented GS<6, T1 or T2a and or initial PSA<10 ng/ml, who were treated with 16 Gy (4 Gy fractions, b.i.d.) HDR-B. The remaining patients were grouped into HR or HR+AD and received 20 Gy (5 Gy fractions, b.i.d.) HDR-B. The planning was optimized using the standard geometric optimization. Biological effective doses (BED) for tumor control and late responding tissue were calculated using a alpha/beta ratio of 1.5 and 3 Gy, respectively. They were matched with bNED, acute and late gastrointestinal (GI) and urological (GU) morbidity, according to the RTOG/EORTC scoring criteria.

Results: Median age of patients was 68 years (range 47-83), with a median follow-up of 41 months (range 18-48). The crude and actuarial biochemical controls (bNED) in 48 months for all patients were 69.5 and 75.3%, respectively. When grouped into LR, LR+AD, HR and HR+AD the actuarial bNED were 78.2, 76, 76 and 72.3% (P=0.89), respectively. Acute GU and GI morbidity G1-2 were seen in 18.5% (20/108) and 10.2% (11/108) of patients with spontaneous regression. Late GI and GU morbidity G1-2 were seen in 12% (13/108) and 4.6 (5/108) of patients, with no need of intervention. No acute or late G3-4 GU or GI morbidity was seen.

Conclusions: There are many advantages in HDR-B, but the most important ones are the capability of on-line dosimetry, quality control and the procedure being very conformal. There is a low incidence of GU and GI acute and late morbidity with acceptable bNED when treating initial and locally advanced prostate cancer with HDR-B as a boost to EBRT, but we still need to wait for results of phase III open trials that analyze HDR-B and conformal therapy.