Background: In patients (pts) with high-volume (HV) metastatic castration sensitive prostate cancer (mCSPC) the addition of six cycles of docetaxel (TXT) to androgen deprivation therapy (ADT) in the CHAARTED and STAMPEDE trials prolonged survival by 10-18 months (mo). Aim of our study was to evaluate the principal patterns of relapse after TXT and their clinical and prognostic significance. Methods: We conducted a multicentric (14 Italian Centers), prospective, observational study enrolling HV mCSPC patients treated with ADT plus early TXT. Clinical and pathological features were recorded. Time to castration resistance (TCR) and overall survival (OS) were estimated by the Kaplan-Meier method and compared with the log-rank test. The Chi-Square test, t-test or Wilcoxon-Mann-Whitney test were used to assess difference between the groups as appropriate. Results: We identified 166 de novo mCSPC pts, with a median age of 64 years (range 38-84). The most common metastatic sites at diagnosis were: bone (93%) and lymph nodes (81%); visceral disease (lung and liver) was present in 36% of cases. 87% of pts had good Eastern Cooperative Oncology Group Performance Status (0-1), the median baseline PSA was 359 ng/ml (range 2.64-5800) and 43% experienced cancer pain. 87% of 158 evaluable pts had a Grade Group (GG) ³4. The majority of pts (81%) completed six cycles of TXT. The median time to PSA nadir was 10.2 months (mo), PSA response > 50% was achieved in 96% of pts and the most common best response reported was partial response (58%). At the time of this analysis, 122 pts (67%) had biochemical or radiographic progressive disease (PD) to TXT and 67 of these (60%) developing new metastatic sites (NMS). No differences with respect of main clinical features was found between NMS pts and nonNMS, with the exception of GG (96% of NMS pts had GG 4-5 vs 74% of nonNMS; p = 0.002). In NMS group we found a higher rate of nodal PD (52% vs 22%, p = 0.001) and higher rate of bone PD (73% vs 47%, p = 0.005) compared to nonNMS. No differences in the rate of visceral PD. With a median follow-up of 27.9 mo, the median TCR was 14.3 mo (95%CI 12.8-16.7), without significant differences between NMS and nonNMS groups. About 90% of progressed pts received first-line treatment for mCRPC disease with similar outcomes. The median OS was 41.8 mo for the overall population, with not significant differences between NMS and nonNMS groups (22 mo and 25 mo). Overall, median OS from mCRPC diagnosis was 19.6 mo, similar in NMS and no-NMS pts (10 mo and 12 mo). Conclusions: In progressive mCSPC pts receiving early TXT, we observed more frequently the development of NMS with an elevated GG and a trophism for bone and lymph nodes. However, the NMS progression does not seem to have a prognostic role. An extended follow up and the prospective data will be provided.