Castration-resistant prostate cancer ( CRPC ) is defined as disease progression during ADT ( androgen deprivation therapy ), with serum testosterone at castrate levels.
The absence of metastases ( M0 ) on traditional imaging ( bone scintigraphy and CT scan ) has been used to identify M0 CRPC disease.
This disease setting exists because of the use of early, long-term ADT for men with non-metastatic prostate cancer.
If ADT is delayed in men with biochemical failure after radical treatment until the site of recurrence is detected, M0 CRPC will be unusual because men will typically only develop castration-resistant disease after the detection of metastases.
Apalutamide significantly increased median metastasis-free survival ( 40.5 months versus 16.2 months, hazard ratio, HR 0.28; 95% CI 0.23-0.35 ) and time to symptomatic progression ( HR 0.45; 95% CI 0.32-0.63 ) as compared with placebo in amulticentre, randomised, placebo-controlled, phase III trial ( SPARTAN ) conducted in 1207 men with high-risk M0 CRPC( baseline PSAmore than 2.0 ng/ml and a PSA doubling time of less than or equal to 10months ).
Data on overall survival are still immature ( HR 0.70; 95% CI 0.47-1.04 ).
The most frequent side-effects observed in the experimental arm were rash, hypertension, fracture, hypothyroidism and mental-impairment disorder.
Enzalutamide was evaluated in patients with high-risk M0 CRPC ( PROSPER trial ). In 1401 patients, Enzalutamide was superior to placebo with regard to the primary end point of median metastasis-free survival ( 36.6 months versus 14.7months, HR 0.29; 95% CI 0.24-0.35 ), and the key secondary endpoints of median time to PSA progression ( 37.2 versus 3.9 months; HR 0.07; 95% CI 0.05-0.08 ) and time to subsequent antineoplastic therapy ( 39.6 versus 17.7 months; HR 0.21; 95% CI 0.17-0.26 ).
Data on overall survival are still immature.
Side-effects most commonly reported in the Enzalutamidegroup were fatigue, hypertension, adverse cardiovascular events and mental-impairment disorders.
Darolutamide was evaluated in the ARAMIS trial, a multicentre, randomised, double-blind, placebo-controlled, phase III trial involving 1509 men with high-risk M0 CRPC and a PSA doubling time of less than or equal to 10 months.
Darolutamide significantly increased the median metastasis-free survival compared with placebo ( median 40.4 months versus 18.4months; HR 0.41; 95% CI 0.34-0.50 ).
Data on overall survival are immature.
Grade 3 or 4 adverse events were reported in 19.5% versus 24.7% of patients receiving placebo and Darolutamide, respectively.
Apalutamide [ ESMO-MCBS v1.1 score: 3 ], Darolutamide [ ESMO-MCBS v1.1 score: 3 ] or Enzalutamide [ ESMO-MCBS v1.1 score: 3 ] should be considered as options for men with M0 ( on bone scan and CT ) CRPC and a high risk of disease progression [ I, B ]. ( Xagena )
Source: Prostate cancer: ESMO Clinical Practice Guidelines, 2020