Metastatic hormone-sensitive prostate cancer: How should it be treated?

Table 1 Characteristics of the randomized phase 3 trials of second-generation antihormonal treatments in metastatic hormone-sensitive prostate cancer

Trial	Treatment	n	Inclusion criteria	Stratification	Main objective	Secondary objectives
LATITUDE (Fizazi K et al[16]) 2017	ABIRATERONE 1000 mg + PREDNISONE 5 mg + ADT; PLACEBO + ADT	597; 602	High risk con ≥ 2 factors: (1) Gleason 8-10; (2) ≥ 3 bone METS; (3) Evaluable visceral METS; and (4) ECOG PS ≤ 2	Visceral METS (yes/no); ECOG PS (0, 1/2)	OSrPFS	Time to pain progression; Time to PSA progression; Development of skeletal events; Time to chemotherapy; Time to new treatment; QoL
STAMPEDE (James et al[17])1 2017	ABIRATERONE 1000 mg + PREDNISONE 5 mg + ADT; ADT	502; 500	Presence of METS	ECOG PS (0/1, 2); AGE (< 70/≥ 70); Use of steroids (yes/no); Research centre; Indication for RT (yes/no); Type of ADT	OS	PFS; Failure-free survival; Cancer-specific survival; Time to skeletal events; Toxicity; QoL
ENZAMET (Davis et al[13]) 2019	ENZALUTAMIDE 160 mg + ADT; ANTIANDROGENS (bicalutamide, flutamide or nilutamide) + ADT	563; 562	Low and high volume defined: (1) Visceral METS; and (2) ≥ 4 bone METS, at least 1 outside vertebral column or pelvis. ECOG PS ≤ 2	Volume (high/low); Docetaxel (yes/no); Comorbidities (0-1/2-3); Antiresorptive treatment (yes/no); Research centre	OS	PFS; PSA response; Adverse effects; QoL; Cost-effectiveness
TITAN (Chi et al[15]) 2019	Apalutamide 240 mg + ADT; PLACEBO + ADT	525; 527	LOW AND HIGH VOLUME DEFINED:(1) Visceral METS + ≥ 1 bone METS; and (2) ≥ 4 bone METS, at least 1 outside vertebral column or pelvis. ECOG PS 0-1; ≥ 1 bone METS on bone scan	Gleason (≤ 7/≥ 8); Docetaxel (yes/no); Geographic region	OS; rPFS	Time to pain progression; Time to opioids; Time to skeletal events; Time to chemotherapy; Time to PSA progression; Survival to 2nd progression; Time to symptomatic local progression; QoL
ARCHES (Armstrong et al[14]) 2019	ENZALUTAMIDE 160 mg + ADT; PLACEBO + ADT	574; 576	ECOG PS 0-1; low and high volume defined:(1) Visceral METS; and (2) ≥ 4 bone METS, at least 1 outside vertebral column or pelvis	Volume (high/low); Docetaxel (no/0-5 cycles/≥ 6)	rPFS; Evaluated at 24 wk	Time to PSA progression; Time to skeletal events; Time to new treatment; Undetectable PSA; Objective response rate; OS; Time to worsening of urinary symptoms; Time to pain progression; Time to castration-resistance; Time to QoL worsening; PROS

¹Only patients with metastases. ADT: Androgen deprivation therapy; METS: Metastases; OS: Overall survival; PROs: Patient-reported outcomes; PS: Performance status; PSA: Prostate-specific antigen; QoL: Quality of life; rPFS: Radiographic progression-free survival; RT: Radiotherapy.