Neoadjuvant chemohormonal therapy improves PFS in locally advanced prostate cancer

Neoadjuvant chemohormonal therapy (NCHT) plus radical prostatectomy (RP) confers significant biochemical progression-free survival (bPFS) benefits relative to neoadjuvant hormonal therapy (NHT) plus RP on patients with high-risk, locally advanced prostate cancer, reports a study.

“Our study suggests that neoadjuvant docetaxel-based chemotherapy could bring significant improvement for patients, and longer follow-up is needed for more supportive evidence,” according to the investigators.

A total of 141 patients with locally advanced prostate cancer participated in this trial and were randomized in a 2:1 ratio to the NCHT group (75 mg/m² body surface area every 3 weeks plus androgen deprivation therapy for 6 cycles) or the NHT group (androgen deprivation therapy for 24 weeks).

More patients in the NCHT group achieved significant bPFS benefits at 3 years compared with those in the NHT group (29 percent vs 9.5 percent; p=0.002). The NCHT group also benefitted from a significantly longer median bPFS time than the NHT group at a median follow-up of 53 months (17 vs 14 months). [J Urol 2024;211:648-655]

There were no significant between-group differences observed in pathological downstaging and minimal residual disease (MRD) rates.

“Our findings indicate that NCHT can deliver similarly remarkable pathological downstaging effects to NHT but offers significant benefits in bPFS,” the investigators said.

Earlier NCHT studies often focused on patients with high-risk prostate cancer who underwent salvage radiation and androgen-deprivation therapy. This could have potentially affected the analysis of disease progression-free time. [J Clin Oncol 2020;38:3042-3050]

The present study addressed the confounding impact of postoperative treatment by not administering salvage therapies such as radiation or hormonal therapy until confirmed biochemical recurrence.

Response rates

“Our study revealed a pathologic complete response (pCR) rate of 1.2 percent (1/83) in the NCHT group, with no cases of pCR in the NHT group,” the investigators said. “Additionally, the NCHT group demonstrated 9.6 percent (8/83) of patients with tumours measuring 0.5 cm or less in the RP specimen, whereas the NCT group had only 2.4 percent (1/41) with such characteristics.”

In previous retrospective studies, pT0 and MRD rates ranged from 5 percent to 10 percent with NCHT for patients with high-risk prostate cancer. [J Clin Oncol 2020;38:3042-3050; Urol Oncol 2019;37:991-998]

“Although our results also suggest a trend toward enhanced pathological responses with NCHT, we did not observe a statistically significant difference between the two groups, which might be attributed to a relatively small sample size,” according to the investigators.

Earlier studies reported a higher pCR rate of nearly 10 percent when suing an intensified neoadjuvant strategy. This approach combines the use of neoadjuvant androgen-deprivation therapy with other agents such as abiraterone or enzalutamide. [Urol Oncol 2019;37:991-998; Prostate Cancer Prostatic Dis 2018;21:364-372; J Clin Oncol 2014;32:3705-3715]

“These encouraging findings have prompted the initiation of multiple ongoing trials that investigate both pathological response and survival benefits,” the investigators said.

“A larger cohort with longer follow-up duration is essential in further investigation,” they noted.