ASTRO 2021: A Prospective Trial of Aggressive Therapy Consisting of Neoadjuvant Chemotherapy and Androgen Deprivation Followed by Prostatectomy and Adjuvant Radiation in High/Very High Risk Prostate Cancer

(UroToday.com) In a session at the American Society for Radiation Oncology (ASTRO) Annual Congress focused on the care of patients with intermediate and high-risk prostate cancer, Dr. Kwok presented results of a prospective trial of aggressive therapy consisting of neoadjuvant chemotherapy and androgen deprivation therapy (ADT) followed by prostatectomy and adjuvant radiotherapy for patients with high and very-high risk prostate cancer.

By way of background, neoadjuvant ADT has not been shown to improve outcomes for patients undergoing prostatectomy. In part, in high risk disease may be associated with androgen independent clones which are not sensitive to ADT. Further, chemotherapy has proven benefit in advanced prostate cancer (mCSPC and mCRPC) with a suggestion of a benefit (though at the expense of toxicity) in the neoadjuvant setting in the PUNCH trial.

Patients in this trial were eligible if they had PSA of 20 ng/mL or greater and Gleason score of 8 of higher. After enrollment, they received LHRH agonist 3 days prior to chemotherapy, with repeating cycles of Adriamycin and docetaxel chemotherapy. This neoadjuvant chemohormonal regime was continued for 6 months prior to radical prostatectomy which was then followed by adjuvant radiotherapy 3-4 months after. Adjuvant radiotherapy was administered with an IMRT technique with 64.8-70.2 Gy in 1.8 Gy per fraction. All patients also received pelvic radiotherapy (45 Gy).

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The primary outcome of this trial was pathologic complete response rate (pCR). The authors assumed a rate of 0-4% with neoadjuvant ADT alone and powered the trial to detect a pCR of 20%. Secondary outcomes included toxicity, pathologic outcomes, effects on apoptosis and proliferation-related markers, and radiographic/recurrence patterns.

Between 202 and 2006, the authors accrued 22 patients. The median PSA was 24.1 ng/mL and median Gleason score was 7. 82% of patients had high risk disease and 18% had very high risk disease. Patients were followed with a median overall follow-up of 10.9 years.

The authors observed acute grade 3 toxicity in 68% of patients and grade 4 toxicity in 32%. However, no patient died due to adverse events. Late grade 3-4 GU toxicity at 15 years was 12.5% while late grade 3-4 GI toxicities were not observed.

No patient had a pathologic complete response. Three patients did not undergo radical prostatectomy due to toxicity of their neoadjuvant therapy and were instead treated with definitive EBRT. In total, 77% of patients received treatment as planned.

Over median overall follow-up of 10.9 years, the 10 year median overall survival was 54.5% and 15 year median overall survival was 31.2%. Disease free survival was 31.8% at 10 years and 22.7% at 15 years while freedom from biochemical failure was 46.2% at 10 years and 46.2% at 15 years.

Dr. Kowk then concluded that despite an aggressive regime comprising neoadjuvant chemohormonal therapy, surgery, and adjuvant radiotherapy, 15 year biochemical no evidence of disease rate was only 46.2% and no patients had pathologic complete response. Therefore, this treatment regime has questionable merit.

Presented by: Young Kwok, MD, Professor of Radiation Oncology, the University of Maryland

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting, Sat, Oct 23 – Wed, Oct 27, 2021.

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