Impact of radiotherapy (RT) combined with androgen deprivation (ADT) versus ADT alone for local control in clinically locally advanced prostate cancer.

Abstract

4505 Background: In locally advanced disease, the combination of RT with ADT is superior to RT or ADT alone. Clear results with an LHRH analog are still pending. We report a phase III trial in locally advanced PCa, comparing a combined modality and ADT only. Methods: In this multicenter, randomized trial, patients < 80 years, with histologically confirmed PCa, T3- 4, or pT3 (biopsy) N0, M0 were included. They were centrally randomised from March 2000 to December 2003 in 2 parallel groups to either ADT (leuprorelin 11.25 mg SR, 1 sc injection every 3 months for 3 years) or the same ADT combined with RT starting within 3 months: 48 ± 2 Gy (pelvic) and 70 ± 4 Gy (prostate) over 7 weeks. The primary endpoint was PFS either biological (ASTRO definition) or clinical. Secondary end points included clinical progression free survival (Clin PFS). Clinical progression was defined as the first of either: > 50% prostatic volume increase compared to its lowest value (sonography based), new regional lymph nodes ( CT) or distant lesions ( CT or bone scan). Analysis was by intent to treat. Results: 273 patients were included, 263 randomised (130 to ADT, 133 to the combined group). Mean age was 70 years, 93% had a T3 disease, mean baseline PSA: 52 and 42 respectively (p = 0.79). With a minimal and median follow up of 60 and 67 months, the 5 years PFS was 60,9% (combined group) vs 8,5% (ADT group) (RR: 5.9 [4.19; 8.42]; p<0,001). The 5-year Clin PFS was 88.7% (combined group) vs 62.3% (ADT group) (p<0.001). The cumulative incidence of loco-regional progression at 5 years was 9.7% (combined group) versus 29% (ADT group) (p<0.0002) and the cumulative incidence of metastatic progression at 5 years respectively 3% vs 10.8% (p<0.018). Conclusions: In patients with locally advanced prostate cancer, addition of local radiotherapy to ADT with 3 years of LHRH significantly reduces the risk of clinical progression. With a still limited follow up of 5 years the benefit is mainly due to loco regional control. For distant metastases a prolonged follow up is needed to see a larger benefit. This reduction of progression confirm that a combined modality should be the standard for patients with a sigificant life expectancy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Takeda Takeda Takeda