Paradoxical significance of endorectal MRI (erMRI) response to neoadjuvant chemotherapy in patients with high-risk localized prostate cancer (HRLPC).

Abstract

23 Background: Intermediate endpoints are desirable to expedite the integration of perioperative systemic therapy in HRLPC. erMRI response has been utilized as an endpoint in neoadjuvant trials but has not been correlated with clinical outcomes. Methods: Data were pooled from two trials exploring neoadjuvant chemotherapy in HRLPC. Trial 1 explored docetaxel for 6 months and Trial 2 explored docetaxel plus bevacizumab for 4.5 months, both prior to radical prostatectomy (RP). erMRI was done at baseline and end of chemotherapy. erMRI response was categorized as PR (>50% decline in largest lesion), MR (25%-50% decline), or no response. PSA response was defined as >50% decline in PSA compared to baseline. Multivariable Cox regression was undertaken to evaluate the association between clinical parameters and biochemical recurrence (BCR). Results: Trial 1 enrolled 19 patients and Trial 2 enrolled 41 patients. Among the 60 evaluable patients in the combined analysis, 20 (33%) achieved a PSA response, 16 (27%) achieved an erMRI PR, and 24 (40%) achieved an erMRI MR. Median follow-up was 4.2 years and 33 of 53 evaluable (62%) patients developed BCR. Median time to BCR from RP was 26.2 months (95% CI 12.5-53.2 mos). The multivariable model is shown in the Table. Conclusions: Response by erMRI does not correlate with decreased likelihood of BCR in patients with HRLPC treated with neoadjuvant docetaxel and may be associated with inferior outcomes. While speculative, this unexpected result could potentially be explained by a higher likelihood of erMRI response in more highly proliferative tumors. These data do not support the use of erMRI response as an endpoint in neoadjuvant chemotherapy trials. [Table: see text]