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High risk Prostate cancer

Baseline PSA of 10 ng/mL or greater, Gleason scores of 8 to 10, and younger age are associated with a shorter time to prostate-specific antigen (PSA) failure following treatment in men with nonmetastatic unfavorable-risk prostate cancer.

A shorter time interval from treatment to PSA failure correlates with worse clinical outcomes in men with prostate cancer.

Patients with high risk, localized or locally advanced prostate cancer have a greater risk of recurrence and death than patient with low risk disease, despite curative intent with radical prostatectomy or radiotherapy and androgen deprivation therapy.

Relapse occurs after radical prostatectomy within five years enough to 50% of patients who have high risk disease, and I’m up to 20% die within 10 years.

A study included 350 men with localized unfavorable-risk prostate cancer who received 6 months of androgen deprivation therapy and radiation therapy with or without docetaxel.

After a median follow-up of 10 years, the researchers identified three factors associated with time to PSA failure. 

PSA levels between 10 ng/mL and 20 ng/mL and Gleason scores of 8 to 10 were associated with a shorter time to PSA failure.

Older age, however, was associated with a lower risk for PSA failure.

The researchers then divided patients into a high- and low-risk category based on these three factors, with the high-risk category defined as younger than 70 years, a PSA of 10 ng/mL or higher, and a Gleason score of 8 to 10.

Clinical disease stage of T3 is associated with a higher recurrence risk

Men in the high-risk group had a significantly higher risk of early PSA failure compared with men in the low-risk group.

The high-risk group had a nearly 44% risk of PSA failure at 3 years.

Men who received pelvic radiation therapy also had a significantly lower risk for PSA recurrence.

The subgroup of men at high risk for early PSA failure, as defined in this study, may benefit from treatment escalation with androgen receptor signaling inhibitors or cytotoxic chemotherapy and should be the subject of a prospective randomized clinical trial.

Perioperative treatment with ADT plus apalutamide is associated with better oncologic outcomes of radical prostatectomy in patients with high risk localized or locally advanced prostate cancer than treatment with ADT plus placebo (PROTEUS study).

The Proteus study is a phase that a clinical trial evaluating addition of oral androgen receptor pathway inhibitor apalalutamide to antigen deprivation therapy before after radical prostatectomy in 2109 patients with high risk localized the locally advanced prostate cancer.
12 total cycles of perioperative treatment (6 months pre-surgery and 6 months post-surgery) comparing apalutamide + ADT versus placebo + ADT. 
Patients receiving apalutamide plus ADT achieved a nearly 9-fold higher rate of pCR/MRD (8.9%) compared to the control arm (1.0%). The combination reduced the relative risk of metastasis or death by 20%. 

Signaled a 29% reduction in the risk of recurrence or death, extending the time to subsequent therapy by nearly 3 additional years.

BRCA2 and ATM are associated with aggressive and metastatic prostate cancer.

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