While continuous therapy remains the official standard of care for mHSPC, there's a growing consensus for individualized de-intensification. For patients with a sustained, undetectable PSA (e.g., for two years), clinicians are increasingly comfortable discussing stopping all treatments to improve quality of life and reduce toxicity.
Shifting the view of prostate cancer from "androgen-driven" to "androgen receptor-driven" provides a new framework. In curative settings, after the androgen receptor is targeted for a defined period, restoring testosterone is seen as logical to improve patient quality of life once the cancer is destroyed.
In metastatic hormone-sensitive prostate cancer (mHSPC), radiographic progression-free survival (rPFS) is no longer seen as a convincing primary endpoint on its own. Clinicians demand a clear signal for overall survival (OS) improvement, citing historical data where early treatment intensification showed significant OS gains.
The mHSPC phase is considered the patient's "best bit of the rest of your life." When considering triplet therapies, clinicians favor options with a fixed, shorter duration of toxicity (like lutetium) over continuous treatments (like capivasertib) to minimize the negative impact on this crucial period of high quality of life.
The endpoint of radiographic progression-free survival (rPFS) is heavily criticized as not being clinically meaningful. The intensive scanning schedule required in trials (e.g., every 8-12 weeks regardless of symptoms) is never replicated in standard clinical practice, making it an artificial measure of patient benefit.
There's a clear clinical consensus to use a PARP inhibitor-based triplet therapy for de novo, high-volume, BRCA-positive mHSPC patients. The rationale is that this subgroup has aggressive disease and may not have a chance for subsequent lines of therapy, making the most potent upfront combination essential.