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.
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.
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.
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.
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.