Dose Escalation with High-Dose-3D-Conformal/IMRT (HD-3D-CRT/IMRT) Compared with Low-Dose 3D-Conformal/IMRT Plus HDR Brachytherapy (LD-3D-CRT/IMRT+HDR-B) for Intermediate- or High-Risk Prostate Cancer: Higher Disease Control and Survival with Lower Toxicity

Abstract

To report early and late toxicity and biochemical outcome in a prospective series of 1343 patients with intermediate- or high-risk clinically localized prostate cancer treated with either HD-3D-CRT/IMRT or with LD-3D-CRT/IMRT+HDR-B. Between 12/1999 and 10/2010, 1343 patients (pts) with PSA›10, Gleason score›6 and/or T2b-T3 N0 M0 prostate cancer entered the study. Pts were prospectively assigned to one of the two treatment groups: 76 Gy HD-3D-CRT or IMRT to the prostate in 38 fractions (group 1; 673 patients) or 46 Gy LD-3D-CRT or IMRT followed by 16 Gy HDR-B given in 2 fractions of 8 Gy (group 2, 672 patients), limiting the maximum rectal dose to 85% of the prescribed dose. Both groups were well balanced taking into account patient’s as well as tumors’ characteristics. Toxicities were scored by the EORTC /RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. All pts completed treatment. None pts included in the group 1 or 2 experienced grade 3 or more rectal toxicity. 86 pts of group 1 (12.8%) and 18 pts of group 2 (2.7%) developed grade 2 rectal toxicity (rectal bleeding or urgency). 45 pts in group 1 (6.7%) and 9 pts in group 2 (1.3%) developed grade 1 rectal bleeding (less than 2 times/week). With a mean follow-up of 102 months, the 10-year free-from-failure survival was 90.7% and 98.3% (p<0.002) in group 1 and 2 respectively; free-from-metastases survival 95.9% and 97.8% (p<0,006)for group 1 and 2 respectively; and cause-specific survival 97.1% and 98.2% (p<0.08). High-dose 3D-EBRT + HDR brachytherapy was a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute as well as late rectal complications were significantly reduced with the combined treatment, compared with what was observed with high-dose conventional, 3D-conformal radiotherapy. Control rates were significantly better with in the HDR-boosted patients as expected by higher effective-dose.