Radiotherapy and concomitant Docetaxel in very high risk prostatic cancer our esperience in the first 30 patients

High-risk prostate cancer patients (cT3, N1, PSA ≥ 20 ng/ml and/or Gleason score ≥8) have a 5-year biochemical failure rate after surgery or radiation of 50% or higher. In this group of patients hormonal therapy (HT) is currently the best systemic treatment option in association with radiotherapy (RT). Due to the heterogeneity of prostate cancer (CaP) cells and attempt to improve the outcome with RT, weekly chemotherapy (CHT) during RT, in localized, high-risk CaP is being explored. Docetaxel has demonstrated a significant anti-tumor effect and impact on survival in hormone refractory CaP and can increase the sensitivity of tumor cells to radiation injury. Patients and Methods: From 2005 to 2010, 30 very high risk patients (pts) were treated with high dose of RT and concomitant Docetaxel. Of these, 17/30 (Group 1) underwent surgery before RT and they were all characterized by pathological advanced disease; 13/30 (Group 2) underwent radical RT and they all presented a clinically advanced disease. Group 1 median age was 65 years (range 57-80); the pathological Gleason Score (pGS) was 8 in 4 and 9 in 13 pts; the pTNM was pT2c in 2, pT3a in 3, pT3b in 10 and pT4 in 2 pts. Nodes were positive in 3 pts; surgical positive margins were found in 6 cases. PSA median level, at diagnosis, was 18 (range 4.25-56.3) and PSA prior to RT was 0.65 ng/ml (range 0.01-4.22); RT median dose, was 70 Gy (range 66-76). Group 2 median age was 73 years (range 65-81); the bioptic GS was 7 in 1, 8 in 4, 9 in 7 pts and 10 in 1 case; cTNM was T3 in 8 and T2 in 5 pts; PSA median level at diagnosis was 9,3 (range 5,27-71,3) and PSA prior to RT was 0,51 ng/ml (0,05-3,83); RT median dose was 80 Gy (range 76-80). Docetaxel was administered in a standard weekly dose (30 mg for pts with m2<2 and 40 mg for pts with m2>=2). Median cycles of CHT was 7 (range 2-8). All pts began HT before and during RT and continued the treatment for 2 years after RT. Results: The median follow up was of 36 months (8-60). Only 6 pts, after a median period of 14 months, presented a recurrent disease (locally or/and to the bones). Median PSA at 3 months after RT was 0.04 (0.01-1.1) ng/ml, and at the last follow up was 0.04 (0.01-1.9). As to the toxicity: gastrointestinal grade I was complained by 18/30 and urological grade I by 12/30 pts. Two patients had to stop CHT infusion after two cycles for systemic toxicity. Conclusion: These preliminary data confirm the feasibility and the tolerability of weekly Docetaxel in combination with RT in men with high risk of disease progression. No pts suffered a performance status worsening during the scheduled treatment. At the median follow up of 36 months, only 20% of pts were relapsed. An increase number of recruited pts and a longer follow up are necessary to confirm the validity of these preliminary results.