Table 1.
Toxicity and oncological outcomes after urethra-steering protocols (limitation of maximal doses, with maximal doses delivered to the urethra lower than maximal doses delivered within the target volume)
| Author | Patients | Study design | RT technique | RT dose | Urethral maximum dose (EQD2, α/β = 3 Gy) |
ADT | Median follow-up | Toxicity scale | Acute GU toxicity | Acute GI toxicity | Late GU toxicity | Late GI toxicity | Oncological outcomes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Herrera et al., 2019 [24] Cloitre et al., 2023 [23] |
33 pts IR = 42% HR = 55% |
Phase I/II prospective trial |
CyberKnife (82%) Tomotherapy |
36.25 Gy / 5 fx Dose escalation up to 50 Gy / 5 fx to the DIL |
D1cc < 39 Gy (84.2 Gy EQD2) D0.1 cc < 41 Gy (91.8 Gy EQD2) |
3% (IR) |
61 months | CTCAE | G2: 15% | G2: 6.1% | G2: 12.1% | G2: 3% | bRFS: 70% |
| Draulans et al., 2020 [21] [22] |
100 pts IR = 25% HR = 75% |
Phase II prospective trial (HYPO-FLAME) |
VMAT |
35 Gy / 5fx Dose escalation to 50 Gy / 5 fx to the DIL |
Dmax < 42 Gy (96.6 Gy EQD2) Dmax delivered (85.4 Gy EQD2) |
31% short-term 31% long-term |
18 months | CTCAE |
Cumulative at 3 months: G2: 34% G ≥ 3: 0% |
Cumulative at 3 months: G2: 5% G ≥ 3: 0% |
Prevalence at 6 months G2: 14% G3: 0% |
Prevalence at 6 months G2: 4% G3: 0% |
NR |
|
Fuller et al., 2018 [28] Fuller et al., 2022 [29] |
259 pts LR = 53% IR = 57% |
Phase II prospective trial | CyberKnife | 38 Gy / 4fx |
Dmax < 45.6 Gy (131.3 Gy EQD2) D10% < 41.8 Gy (112.4 Gy EQD2) D50% < 39.9 Gy (103.6 Gy EQD2) |
No | 5.5 years | CTCAE |
G2: 35.1% G3: 1.1% |
G2: 6.9% G3: 0% |
Cumulative incidence G ≥ 2: 19.2% |
Cumulative incidence G2: 4.1% |
10-year bRFS: LR: 100% IR-favorable: 84.3% IR-unfavorable: 68.4% |
| McDonald et al., 2018 [20] |
26 pts LR = 33% IR = 77% |
Prospective pilot trial | VMAT |
36.25 Gy /5fx Dose escalation to 40 Gy /5fx to the DIL |
Dmax ≤ 38.78 Gy (83.5 Gy EQD2) | 30% | At least 3 months | NR |
G2: 7.7% G3: 0% |
G2: 7.7% G3: 0% |
NR | NR | NR |
|
Brand et al., 2019 [25] Tree et al., 2022 [7] |
874 pts (414 pts in the SBRT arm) |
Phase III prospective randomized trial (PACE-B) |
VMAT IMRT CyberKnife |
36.25 Gy and 40 Gy/5fx |
V42Gy (95.7 Gy EQD2) < 50% V44Gy (103.8 Gy EQD2) < 20% |
No | 24 months | CTCAE |
Worst acute toxicity: G ≥ 2: 30.9% |
Worst acute toxicity: G ≥ 2: 15.6% | Cumulative incidence G ≥ 2: 32.3% | Cumulative incidence G ≥ 2: 12.5% | NR |
| Pryor et al., 2019 [27] |
135 pts IR = 76% HR = 26% |
Phase II prospective trial (PROMETHEUS) |
VMAT / IMRT |
Prostate: 46 Gy /23fx Followed by a boost: 19-20 Gy /2fx |
D0.1 cc < 20.9 Gy (total of 102 Gy EQD2) – 22 Gy (total of 107.6 Gy EQD2) |
36% short-term 18% long-term |
24 months | CTCAE |
G2: 26.6% G3: 0% |
G2: 4.4% G3: 0% |
Cumulative incidence G ≥ 2: 24.9% G ≥ 3: 2.2% |
Cumulative incidence G ≥ 2: 4.5% G ≥ 3: 2% |
NR |
| Kishan et al., 2023 [36] |
156 pts IR = 61% HR = 23% vHR = 9% N + = 7% |
Prospective randomized phase III trial (MIRAGE) | MR-guided vs CT-guided SBRT | 40 Gy /5fx | Dmax < 42 Gy (95.7 Gy EQD2) |
CT-arm: 74% MRgRT: 62% |
At least 3 months | CTCAE |
MRgRT: G ≥ 2: 24.4% CT-guided: G ≥ 2: 43.4% |
MRgRT: G ≥ 2: 0% CT-guided: G ≥ 2: 10.5% |
NR | NR | NR |
RT radiation therapy, GU genitourinary, GI gastrointestinal, VMAT volumetric arc therapy, pts patients, LR low-risk, IR intermediate-risk, HR high-risk, NR non reported, DIL dominant intraprostatic lesion, IMRT intensity-modulated radiation therapy, G grade, bRFSbiochemical relapse-free survival