High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up

摘要

The institutional review board approved this retrospective study. A total of 200 consecutive patients with National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer were treated using HDR brachytherapy between December 2003 and January 2008. Clinical Stage T3a, a Gleason score of 8–10, and a prostate-specific antigen (PSA) level 20 ng/ml were defined as HR factors. Clinical stage T3b–T4 was defined as the VHR factor. Patients with a single HR factor were classified as HR, and patients with at least the single VHR factor or two HR factors were classified as VHR. Pretreatment evaluation included clinical history, physical examination, blood laboratory findings, pelvic computed tomography (CT), and a bone scan. Magnetic resonance imaging (MRI) was recommended on request. No lymph node dissection was performed. Patients with positive lymph nodes or distant metastasis were excluded. International Prostate Symptom Score (IPSS), previous transurethral resection, and prostate volume were not considered in the selection criteria. All patients initially underwent ≥6 months (mean, 14 months; median, 12 months; range, 7–74 months) of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after completion of radiotherapy. Neoadjuvant ADT comprised combined androgen blockade with monthly gonadotropin-releasing hormone agonist (GnRHa) injections and 125 mg of flutamide twice daily. Adjuvant ADT consisted of monthly injections of GnRHa. Briefly, patients in the operating room were placed in a lithotomy position under epidural anesthesia. Treatment was initiated using placement of a closed transperineal hollow needle under transrectal ultrasound guidance. Multiple 20- to 25-cm-long, closed-end, 15-G plastic hollow needles were inserted transperineally using a Syed-Neblett plastic template (Alpha-Omega Services, Bellflower, CA). Routinely, 18 needles were implanted. Twelve needles were inserted in the peripheral portion and six needles were inserted in the central portion of the prostate. Flexible cystoscopy was conducted to check that the urethra had not been penetrated by the implanted tubes. The needle tips were left within the urinary bladder, 1.5 cm above the sonographically or cystoscopically defined base of the prostate. Metallic marker seeds were placed transperineally into the base and apex. Duration of follow-up was calculated from the start of HDR brachytherapy. Toxicities were evaluated using the Radiation Therapy Oncology Group scale [7] at every visit, and all patients were followed up at 3-month intervals during the first year and at 3- to 6-month intervals thereafter. Acute toxicity was defined as toxicity occurring ≤3 months after implantation and late toxicity as that occurring after 3 months. Median follow-up for all patients was 61 months (range, 25–94 months). Biochemical failure was defined according to the Phoenix definition [8]. Biochemical non-evidence of disease rate (bNED) was calculated for all living patients and reflected biochemical failures. Freedom from clinical failure rate (FFcF) was calculated for all living patients and reflected all clinical events (local, regional or distant failure) and salvage ADT. OS reflected all deaths, cancer-related or otherwise. Univariate analysis (log-rank) was used to examine the predictive value of patient-related factors (clinical T stage (≤T2c vs ≥T3a), Gleason score (≤7 vs ≥8), initial PSA (≤20 ng/ml vs 20 ng/ml), NCCN criteria (HR vs VHR), prostate volume (≤20 ml vs 20 ml), age (≤70 years vs 70 years)) and treatment-related factors (D90 (≤6.3 Gy/fraction vs 6.3 Gy/fraction) and duration of neoadjuvant ADT (12 months vs ≥12 months)). To evaluate interactions and independent influences on factors, multivariate analysis was performed using Cox regression analysis. Differences were regarded as statistically significant at the P 0.05 level. The 3- and 5-year bNED were 96.0% (HR, 98.9%; VHR, 92.6%) and 90.6% (HR, 97.8%; VHR, 81.9%), respectively (Fig. 1). The corresponding values for FFcF were 97.4% (HR, 99.0%; VHR, 96.3%) and 95.2% (HR, 97.7%; VHR, 92.1%), respectively. The 3- and 5-year OS rates were 97.7% (HR, 100%; VHR, 95.1%) and 96.9% (HR, 100%; VHR, 93.3%), respectively. Nine patients experienced clinical progression, including 4 patients with bone metastasis, 1 patient with lung metastasis, 1 patient with distant lymph-node metastasis, 1 patient with regional lymph-node metastasis, 1 patient with positive biopsy, and 1 patient who underwent salvage ADT. Five patients died during follow-up including 1 patient who died of interstitial pneumonitis, 1 patient who died of bladder cancer, 2 patients who died of prostate cancer, and 1 patient who died due to an accident. The highest Radiation Therapy Oncology Group (RTOG)-defined acute genitourinary (GU) toxicities were Grade 2 in 19 patients (10.7%) and Grade 3 in 10 patients (5.6%). No patients experienced ≥