TABLE 1.
Characteristics of the principal prospective studies focusing on ART versus SRT.
| EORTC 22911 [9] | SWOG 8794 [8] | ARO 96-02 [5] | FP-FINROG-0301 [10] | RADICALS-RT [13] | TROG 08.03/ANZUP RAVES [3] | GETUG-AFU 17 [14] | |
|---|---|---|---|---|---|---|---|
| Design | ART within 16W WW | ART WW | ART WW SRT for PSA persistence | ART within 12 W WW | ART within 26 W SRT within 2 M from BCR | ART within 6 M SRT 4 M from BCR non-inferiority | ART within 3–6 M SRT at BCR ADT for 6 M for all patients |
| Nr. pts. | 1,005 | 425 | 307 | 250 | 1,396 | 333 | 424 |
| mFU (years) | 10.6 | 12.6 | 9.3 | 9.0 | 4.9 | 6.1 | 6.2 |
| Main Inclusion criteria | ≤75 Y old PS 0–1 WHO pT2-3N0M0 and ≥1 RF:ECE—77%SVI—25.5%.PSM—62.6% | PS 0–2 ≥1 RF: pT3a/b– 67%SVI—10% both– 22%p/cN0 M0 PLDN allowedno signs of incontinece | <76 Y old PS 0–1 WHO pN0 M0ECE—45%SVI—17% pT3c/pT4—36%PSM—68%- non-detectable PSA after RP | pT2N0M0 and PSM pT3a N0M0no SVI (pT3b)c/pN0M0 | Postoperative PSA ≤0.2 ng/mL and ≥1 RF: pT3-4–76%PSM—63%GS ≥ 7–93% iPSA 10 ng/mL | PS 0–1 PSA ≤0.2 ng/mL and ≥1 RF:ECESVI—20%PSM—67%GS ≥ 7–97% | PS 0–1 pT3–pT4a ECE—77% SVI—21% GS ≥ 7–90% pNx (no PLND)/pN0(PLND)PSM |
| Endpoints | 1o bRFS | 1o MFS | 1o bRFS | 1o bRFS | 1o CSS | 1o bPFS | 1o EFS |
| 2o LRFS, MFS, OS, CSS, toxicity, QoL | 2o bRFS, OS, QoL | 2o MFS, OS, toxicity, QoL | 2o OS, CSS, toxicity | 2o FFDM, OS, bPFS, toxicity, QoL | 2o bRFS, OS, QoL | 2o MFS, OS, toxicity, QoL | |
| RT | 60 Gy/30 fr. 2D-RT | 60–64 Gy/30–32 fr., 2D-RT | 60Gy/30 fr. 3D-RT | 66.6 Gy/37 fr., 3D-RT | 66Gy/33 fr. or 52.5Gy/20 fr. | 64 Gy/32 fr. RT-PLND and ADT not allowed | 66Gy/33fr. |
| RT-PLND allowed (7% ART, 3% SRT) | RT-PLND allowed | ||||||
| ADT allowed: (24% ART, 27% SRT) | ADT (triptorelin 6M) allowed (18% ART and 24% SRT) | ||||||
| PSA after RP > 0.2 ng/mL | 29.9% | 33% | 0% in the ART | ART: 70%; WW: 65% | NA | NA | NA |
| Pre-RT PSA: | |||||||
| ≤0.2: 70.3% ART | |||||||
| 68.6% WW | |||||||
| >0.2: 28.7% ART | |||||||
| 31.2% WW | |||||||
| Definition of BCR (ng/mL) | >0.2 | >0.4 | >0.05 | >0.4 | >0.4 after RP or >2.0 ng/mL anytime | >0.4 | >0.4 ng/mL within 6 M after RT or >1.0 ng/mL anytime |
| Rate of SRT in WW | 41% | 37% | NA for ART | 86% | NA | NA | NA |
| Median PSA before SRT | 1.7 ng/mL in WW-arm | 0.75–1.0 ng/mL in WW-arm | NA for ART | 0.7 ng/mL in WW-arm | 0.2 ng/mL (0.1–0.3) | >0.2 ng/mL - 50% | >0.24 ng/mL - 54% |
| Mean time to SRT | 2.9 y | 33% immediately | NA for ART | 32% 5y after RP | 33% immediately | 23 M (4–100) | |
| 87% within 6 M | 33% 8 y after RP | 87% within 6 M | |||||
| 37% LR | |||||||
| Results: | |||||||
| bRFS | 10 y ART 60.6% vs. SRT 41.1% | mFU ART 60.7% vs. SRT 47.4% | 5 y ART 77% vs. SRT 54% | 10 y ART 82% vs. SRT 61% | 5 y ART 85% vs. | 5 y FFBP ART 86% vs. SRT 87% (HR 1.12, p = 0.15) | 5 y EFS: ART 92% vs. SRT 90% (HR 0.81, p = 0.42) |
| 10 y ART 56% vs. SRT 35% | SRT 88% (p = 0.56) | 8 y FFBP ART 80% vs. SRT 77% | |||||
| OS | 10 y ART 76.9% vs. SRT 80.7% (p = 0.3407) | mOS: ART 15.2 y vs. SRT 13.3 y (HRART = 0.72, p = 0.023) | 5.5 y: ART 96.6% vs. SRT 95% | 10 y ART 92% vs. SRT 87% (p = 0.4) | 9 y ART NA vs. SRT 96% | 5 y ART 99% vs. SRT 98%8 y ART 92% vs. SRT 97% | 5 y ART 96% vs. SRT 99% (HR 1.60, p = 0.25) |
| mFU ART 74% vs. SRT 66% | 9 y: ART 86.5% vs. SRT 85.5% | ||||||
| CSS | 10 y | NA | NA | 10 y | NA | NA | ART 99% vs. |
| ART 96.1% vs. SRT 94.6% | ART 99% vs. SRT 99% | SRT 99% | |||||
| MFS | 10 y ART 89.9% vs. SRT 89% | mFUART 57% vs. SRT 46% (HRART = 0.71, p = 0.016) | 5.5 y ART 98% vs. SRT 96.9%9 y ART: 84.3% vs. SRT 85.1% | 10 y ART 98% vs. SRT 96% (p = 0.4) | 9 y FFDM ART NA vs. SRT 9% | 5 y FFLDP ART 96% vs. SRT 96% 8 y FFLDP ART 93% vs. SRT 91% | NA |
| Toxicity: | |||||||
| Acute toxicity | GU ≥ G2: ART 21.3% vs. SRT 13.5%GI ≥ G2: ART 11% vs. SRT 4% | NA | GU ≥ G2: ART 2% vs. SRT 0%GI ≥ G2: ART 1.2% vs. SRT 0% | NA | GU < 2 years: Any G: ART 54% vs. SRT < 26% ≥ G3: ART 12% vs. SRT <7% | GU ≥ G2: ART 70% vs. SRT 54%GI ≥ G2: ART 14% vs. SRT 10% | GU ≥ G2: ART 17% vs. SRT 4% ≥ G3: ART 3% vs. SRT 2% |
| GI ≥ G2: ART 2.5% vs. SRT 1.9% | GI < 2 years: Any G: ART 62% vs. SRT 25% ≥ G3: ART 2% vs. SRT <2% | ||||||
| Late toxicity | Any: ART 70.8% vs. SRT 59.7%≥G3: ART 5.3% vs. SRT 2.5% | Any: ART 23.8% vs. SRT 11.9% | Any: ART 21.9% vs. SRT 3.7%≥G3: ART 1% vs. SRT 0% | Any: ART 56% vs. SRT 40% | GU > 2 years: Any GU: ART 40% vs. SRT 19% ≥ G3: ART 9% vs. SRT <5% | NA | GU: Any: ART 73% vs. SRT 29% ≥ G2: ART 27% vs. SRT 7% ≥ G3: ART 6% vs. SRT 1% |
| GI > 2 years: ART 33% vs. SRT 15% ≥ G3:ART 3% vs. SRT < 2% | GI: Any: ART 44% vs. SRT 20% ≥ G2: ART 8% vs. SRT 5% ≥G3: ART 4% vs. SRT <1% | ||||||
| Erectile dysfunction | NA | NA | NA | NA | NA | ≥G2: | Any: |
| ART 98% vs. | ART 36% vs. | ||||||
| SRT 96% | SRT 13% | ||||||
| ≥G2: | |||||||
| ART 28% vs. | |||||||
| SRT 8% | |||||||
| ≥G3: | |||||||
| ART 4% vs. | |||||||
| SRT 1% | |||||||
mFU, medical follow-up; Nr. pts., Number of patients; M, month; W, weeks; y, years; RP, radical prostatectomy; ART, adjuvant radiotherapy; WW, watch and wait/observation; SRT, salvage radiotherapy; BCR, biochemical relapse; RF, risk factors for recurrence; PS, performance status; ECE, extracapsullary extension; SVI, seminal vesicle infiltration; PSM, positive surgical margins; GS, Gleason score; PLND, pelvic lymph node dissection; PSA, prostate specific antigen; iPSA, initial PSA; ADT, androgen deprivation therapy; RT, radiotherapy; fr., fractions; bRFS, biochemical relapse-free survival; PFS, progression-free survival; LRFS, local relapse-free survival; MFS, metastasis-free survival; OS, overall survival; CSS, carcinoma-specific survival; EFS, event-free survival; QoL, quality of life; FFDM, Freedom from distant metastases; FFBP, freedom from biochemical progression; FFLDP, freedom from local and distant progression; LR, local relapse; GU, genitourinary toxicity; GI, gastrointestinal toxicity; NA, not applicable.
The bold value means no patient in the ART arm.