A feasibility trial investigating inductive apalutamide therapy combined with radical prostatectomy in patients with locally advanced T4 high risk prostate cancer: First results of the prospective phase II INDUCTA study.

Abstract

370 Background: Locally-advanced, inoperable T4 prostate cancer (PCa) is a challenging scenario usually treated by combined systemic treatment and/or radiotherapy. To date, no prospective trial examining inductive hormonal therapy to achieve operability in such patients exists. Retrospective data demonstrated successful treatment with radical prostatectomy at PSA nadir. While only a minority of these patients was cured, long-term survival with persistent sensitivity to androgen deprivation therapy (ADT) was observed in the majority. The INDUCTA trial aimed to prospectively investigate whether combined inductive treatment with ADT and Apalutamide reliably induces operability in T4 PCa. Methods: INDUCTA enrolled patients with cT4 PCa, considered inoperable (confirmed by DRE and mpMRI) with no prior radio- or antihormonal therapy and without metastases in conventional imaging (CT and bone scan). After 6 months of ADT and Apalutamide 240 mg daily, local disease stage and operability were reassessed. If operable, patients received robot-assisted radical prostatectomy (RARP). We report the proportion of patients achieving operability after combined inductive therapy (primary endpoint), together with peri- and early postoperative results. Results: Of 27 patients screened, 21 (mean age 69.4±7.2 yrs) entered the trial and completed treatment (compliance 96.8%). At diagnosis, median PSA was 47.4 ng/mL (5.4-395). Operability was confirmed in all 21 after inductive therapy. Median PSA nadir after ADT was 0.05 ng/mL (0.01-1.32). While one operable patient did not undergo surgery due to cardiac deterioration, RARP was performed in 20 patients. There were no rectal injuries and no grade IV or V complications, while grade III occurred in only two cases. Table 1 illustrates the perioperative parameters and final RARP pathology. Quality of life (FACT-G, FACT-P,EQ-5D-3L) showed no baseline deterioration. Conclusions: Inductive therapy with ADT and Apalutamide leads to essential downstaging enabling RARP in 100% of patients. These results set the stage for a new standard of care treatment concept for T4 PCa. Besides disease control preventing future complications, removal of the locally advanced primary tumor should positively influence the further course of disease and even give those affected a chance to be cured. Clinical trial information: 2021-003523-16. Perioperative and pathological parameters. Total, N = 20 Duration of surgery [min, median (range)] 163 (106 - 244) Blood loss [mL, median (range)] 175 (30 - 800) Duration of hospitalization [days, median (range)] 7 (3 - 53) Catheter: days in situ [median (range)] 5 (3 – 93) n % Pathological T stage pT2c 1 5 pT3a 7 35 pT3b 12 60 Pathological evaluation of regional lymph nodes pN0 9 45 pN1 11 55 Surgical margin status negative 13 65 positive 7 35