Table 2.
Toxicity and oncological outcomes after urethra dose-reduction protocols (prescription of a lower dose on the whole urethra, or with maximal doses delivered to the urethra lower than the dose of prescription to the prostate gland)
| Author | Patients | Study design | RT technique | RT dose | Urethral dose prescription | Dose constraints (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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Bruynzeel et al., 2020 [30] Tetar et al., 2021 [34] |
101 pts LR = 4% IR = 37% HR = 59% |
Phase II prospective trial | MRgRT | 36.25 Gy / 5 fx | 32.5 Gy /5fx | D2% < 34.8 Gy (69.2 Gy EQD2) |
41% short-term 41% long-term |
At least 3 months | CTCAE | G ≥ 2: 19.8% | G ≥ 2: 3% | G2: 3.1–5.1% | 0% | 2-year bRFS: 96.7% |
| Greco et al., 2022 [37] |
444 pts LR = 4.1% IR = 84% HR = 11.9% |
Phase II prospective trial | VMAT | 45 Gy /5fx | None | D1cc < 36 Gy (73.4 Gy EQD2) | 36% | 58 months | RTOG |
G2: 6.8% G3: 0% |
G2: 0.5% G3: 0% |
Cumulative incidence: G ≥ 2: 5.3% |
Cumulative: G ≥ 2: 1.1% |
7-year bRFS: 86.2% |
| Greco et al., 2021 [38] |
30 pts IR = 100% |
Phase II prospective randomized trial (PROSINT) |
VMAT | 45 Gy /5fx | None |
Dmax < 42.75 Gy (98.7 Gy EQD2) D1cc < 36 Gy (73.4 Gy EQD2) |
No | 48 months | RTOG | G ≥ 2: 0% | G ≥ 2: 0% |
Cumulative incidence: G2: 17% |
G ≥ 2: 0% | 4-year bRFS: 85.7% |
| 24 Gy /1fx |
Dmax < 22.8 Gy (117.6 Gy EQD2) D1cc < 19.2 Gy (85.2 Gy EQD2) |
G ≥ 2: 0% | G ≥ 2: 0% |
Cumulative incidence G2: 11.4% Urethral strictures: 6.6% |
G ≥ 2: 0% | 4-year bRFS: 77.1% | ||||||||
| Magli et al., 2021 [36] | 59 pts | Phase II prospective trial | IMRT | 40 Gy / 3 fx | 33 Gy /3fx | D0.1 cc < 33 Gy (92.4 Gy EQD2) | 3 months if prostate size > 80cm3 | At least 12 months | CTCAE | G ≥ 2: 13.8% | G2: 8.5% |
Prevalence at 12 months: G2: 0% |
G2: 0% | NR |
| Parsai et al., 2020 [35] |
35 pts LR = 9% IR = 40% HR = 51% |
Prospective pilot study | VMAT |
50 Gy /5fx 36.25 Gy /5fx to HDAZ |
36.25 Gy /5fx |
Dmax < 50 Gy (130 Gy EQD2) D1cc < 45 Gy (108 Gy EQD2) |
No: 45% Short-term: 50% Long-term: 5% |
46 months | CTCAE |
G2: 19.4% G4: 2.9% |
G2: 0% G4: 2.9% |
12-months incidence: G2: 25% G4: 2.9% |
12-months incidence: G2: 5.6% G4: 2.9% |
3-year bRFS: 88% LR: 100% IR: 89.5%-100% HR: 82.3% |
| Zilli et al., 2019 [39] | 6 pts |
Phase I prospective trial (ONE SHOT) |
VMAT | 19 Gy /1fx | 17 Gy /1fx | D2% < 18.2 Gy (77.1 Gy EQD2) | No | At least 3 months | CTCAE |
G2: 33% G ≥ 3: 0% |
G2: 0% | NR | NR | NR |
|
Zilli et al., 2020 [32] Zilli et al., 2023 [31] |
170 pts LR = 22% IR = 64% HR = 14% |
Phase II randomized trial (once a week vs every other day) |
IMRT / VMAT | 36.25 Gy /5fx | 32.5 Gy /5fx | D2% < 34.8 Gy (69.2 Gy EQD2) | 45% | 77/78 months | CTCAE | Worst G2: 17/19% | Worst G2: 2/0% |
Cumulative: G2: 21.6% G3: 0.6% Incidence: G2 8.3% and 7.3% (5-yr) |
Cumulative: G2: 9.3% G3: 0% Incidence: G2 < 2% (5- yr) |
5-year bRFS: 92.2% (every other day) – 93% (once a week) |
RT radiation therapy, GU genitourinary, GI gastrointestinal, MRgRT magnetic resonance guided radiation therapy, NR non reported, bRFS biochemical relapse-free survival, pts patients, LR low-risk, IR intermediate-risk, HR high-risk, IMRT intensity modulated radiation therapy, HDAZ high dose avoidance zone, NS non specified, G grade, bRFS biochemical relapse-free survival