De‑escalation therapy in metastatic prostate cancer: can some men safely stop ADT + ARPI after a deep response?

For men with metastatic prostate cancer, the current standard is continuous androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) such as abiraterone, enzalutamide, apalutamide, or darolutamide. This approach improves survival but comes with substantial clinical and financial toxicity: fatigue, metabolic changes, sexual dysfunction, bone loss, cardiovascular risk, and long‑term treatment costs. The key question is whether, in patients who achieve a deep and durable response, it is possible to safely pause treatment for a meaningful period without compromising cancer control. A new retrospective study, published in Clinical Genitourinary Cancer, suggests that in carefully selected patients the answer may be yes—especially for those who start with metastatic hormone‑sensitive disease (mHSPC).

The study was a retrospective cohort including 69 men with metastatic hormone‑sensitive (mHSPC) or castration‑resistant prostate cancer (mCRPC) treated between January 2014 and May 2025. All patients received ADT plus an ARPI for at least 12 months without progression and achieved deep biochemical and radiological responses before planned treatment cessation. The authors evaluated treatment‑free survival (TFS), progression‑free survival (PFS), and duration of response upon rechallenge after progression.
Median induction (on‑treatment) duration was 26 months, and median TFS after stopping therapy was 35 months. Two‑ and five‑year TFS rates were 56.2% and 33.8%, respectively.
On multivariable analysis, the only independent predictor of a durable treatment break was initial hormone sensitivity (mHSPC vs mCRPC), with mHSPC associated with longer TFS (HR 2.27; P = .029).
In the mHSPC subgroup, median PFS from induction start was 65.5 months, while median TFS was not reached, indicating that more than half of these patients remained treatment‑free at last follow‑up. Among 33 patients who progressed after stopping therapy, 27 were rechallenged with the same ADT + ARPI regimen, achieving a 96.3% response rate. The authors of this study conclude that a planned treatment holiday after a deep response to modern ADT plus ARPI is feasible and durable, particularly in mHSPC, and that many deep responders can remain off therapy longer than their initial induction period without evident loss of treatment sensitivity upon rechallenge.

These findings align with prospective data presented in 2026, most notably the phase II A‑DREAM / Alliance A032101 trial, which tested a similar “stop‑and‑watch” strategy in exceptional responders with metastatic hormone‑sensitive disease. In A‑DREAM, 78 men with metastatic castration‑sensitive prostate cancer received ADT for 540–750 days and an ARPI for at least 360 days, then stopped both therapies if PSA was below 0.2 ng/mL and disease was stable or improving. Patients were monitored closely with PSA every three months and imaging every six months, restarting treatment for predefined triggers such as PSA above 5 ng/mL, radiographic progression, or new symptoms. At 18 months, 41% of patients remained treatment‑free with testosterone recovery, and 58% were still off therapy at that timepoint. Median time off treatment was 24.5 months, with an estimated 24‑month radiographic progression‑free survival of 80.7% and overall survival of 96.0%. These results support the concept that, in a highly selected group of exceptional responders, a supervised break from hormonal therapy is possible for a meaningful period, with recovery of testosterone and quality of life, before treatment needs to resume.

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