Table 1.
Research trials on multimodal combination therapy related to omCSPC.
| Author | Trials | Number of metastasis | Treatment (patients) | Control (patients) | Results | Safety |
|---|---|---|---|---|---|---|
| Boevé LMS (54) | HORRAD | ≥1† | ADT + EBRT[216] | ADT[216] | mOS: 45 (40.4–49.6) vs 43 (32.6–53.4) months; mPSA-PFS: 15 (11.8–18.2) vs 12 (10.6–13.4) months | − |
| Parker CC (35) | STAMPEDE | ≥1† | ADT+RT[1032] | ADT[1029] | FFS: HR 0.76 | Grade ≥3 AEs: 39% vs 38% |
| Decaestecker K (42), Ost P (43) | STOMP | ≤3‡ | MDT +AS[31] | AS[31] | mADT-FS: 21 (14–29) vs 13 (12–17) months | Grade 1 AEs: 19% vs – |
| Armstrong AJ (55), Armstrong AJ (56) | ARCHES | ≤5† | Enzalutamide+ADT[224] | PBO+ADT[221] | OS: HR 0.59; rPFS: HR 0.27 | Grade 3 AEs: 27% vs 26%; Grade >3 AEs: 21% vs 20% |
| >5 | Enzalutamide+ADT[220] | PBO+ADT[242] | OS: HR 0.55; rPFS: HR 0.33 | Grade 3 AEs: 20% vs 22%; Grade >3 AEs: 14% vs 20% | ||
| Saad F (57) | ARANOTE | ≥1† | Darolutamide+ADT[446] | PBO+ADT[223] | OS: HR 0.81; rPFS: HR 0.54 | Grade 3–4 AEs: 30.8% vs 30.3%; Grade 5 AEs: 4.7% vs 5.4% |
| Chi KN (58), Chi KN (59) | TITAN | ≥1† | Apalutamide+ADT[525] | PBO+ADT[527] | 24-month OS: 82.4% vs 73.5%; 24-month rPFS: 68.2% vs 47.5% | Grade 3–4 AEs: 42.4% vs 40.8% |
| Sweeney CJ (60) | ENZAMET | ≥1† | TS+Enzalutamide[563] | TS+NSAA[562] | 5-year OS: 67% vs 57%; PSA-PFS: 54% vs 25%; cPFS: 56% vs 28% | Grade 3–4 AEs: 47% vs 33%; Grade 5 AEs: 2% vs 2% |
| Agarwal N (61) | SWOG-1216 | ≥1† | ADT+Orteronel[638] | ADT+ Bicalutamide[641] | mOS: 47.6 vs 23.0 months; mPFS: 81.1 vs 70.2 months | Grade 3–4 AEs: 43% vs 14% |
| Fizazi K (62), Fizazi K (63) | LATITUDE | ≥3† | AAP+ADT[597] | PBO+ADT[602] | mOS: NR vs 34.7 months; mrPFS: 33.0 vs 14.8 months | Grade 3–4 AEs: 63% vs 48%; Grade 5 AEs: 28% vs 24% |
| Kyriakopoulos CE (64) | ECOG3805 CHAARTED | ≤3† | ADT+DTX[134] | ADT [143] | mOS: NR | – |
| >3 | ADT+DTX[263] | ADT [250] | mOS: 51.2 vs 34.4 months | – | ||
| Marvaso G (41) | RADIOSA | ≤3‡ | ADT + SBRT[53] | SBRT[52] | mPFS: 32.2 (22.4–NR) vs 15.1 (12.4–13.4) months | Grade ≥3 AEs: 2% vs 0% |
| Gravis G (65) | GETUG-AFU 15 | ≥1† | ADT +DTX[192] | ADT[193] | mOS: 58.9 (50.8–69.1) vs 54.2 (42.2–NR) months | – |
| Deek MP (66) | − | ≤5‡ | MDT+ADT[105] | MDT[158] | 5-year bPFS: 24% vs 29%; dPFS: 11% vs 19%; cPFS: 41% vs 9% | – |
| Tang C (40) | EXTEND | ≤5† | RP+intermittent ADT[43] | intermittent ADT[44] | mPFS: NR vs 15.8 (13.6–21.2) months | Grade 3 AEs: 7.0% vs 4.5% |
| Conde-Moreno AJ (67) | SBRT-SG 05 | ≤3† | ADT + SBRT[67] | − | bRFS/PFS: 1-yr 91%/92%, 2-yr 73.7%/81%, 3-yr 50.6%/67% | Grade ≥3 AEs: None |
| Fizazi K (68) | PEACE-1 | ≥1† | ADT+DTX +AA[335] | ADT+DTX[335] | OS: HR 0.75; rPFS: HR 0.50 | Grade ≥3 AEs: 63% vs 52% |
| Hussain M (69) | ARASENS | ≤3† | Darolutamide+ADT+DTX [154] | PBO+ADT+DTX [146] | OS: HR 0.68 | Grade 3–4 AEs: 70.1% vs 61.1% |
| >3 | Darolutamide+ADT+DTX [497] | PBO+ADT+DTX [508] | OS: HR 0.69 | Grade 3–4 AEs: 64.9% vs 64.2% | ||
| Turner PG (70) | ADRRAD | ≤3† | ADT +RP+Radium-223[30] | − | mPFS: 20.5 months | Grade 3 AEs: 20% |
| Nickols NG (71) | SOLAR | ≤5† | RT\RP+AAT+SBRT[24] | − | Primary endpoint met: 20/24 (no progression); 3/4 non-responders progressed | Grade ≥3 AEs: 12.5% |
| Nikitas J (72) | SATURN | ≤5‡ | ADT+AAT+SBRT[26] | − | PSA <0.05 ng/ml at 6 months: 13/26 patients | Grade 2/3 AEs: 21%/21% |
† Synchronous omCSPC.
‡ Metachronous omCSPC.
ADT, androgen deprivation therapy; EBRT, external beam radiation therapy; mOS, median overall survival; mPSA-PFS, median prostate-specific antigen-progression-free survival; RT, Radiotherapy; FFS, Failure-Free Survival; HR, hazard ratio; AEs, adverse events; G1-5, grade1-5; MDT, Metastases-directed therapy; AS, active surveillance; mADT-FS, median ADT-free survival; PBO, placebo; rPFS, radiographic progression-free survival; DTX, Docetaxel; SBRT, stereotactic body radiation therapy; mPFS, median progression-free survival; AAP, abiraterone acetate and prednisone; NR, not reached; bPFS, Biochemical progression-free survival; dPFS, distant progression-free survival; cPFS, combined biochemical progression-free survival; RP, radical prostatectomy; bRFS, biochemical recurrence-free survival; TS, testosterone suppression; NSAA, non-steroidal antiandrogen (bicalutamide, nilutamide, or flutamide).