Table 2.
Studies using vHDRB.
| Author/Study | Year | N | Risk | Median Follow-Up (Months) | Conventional Dose | Pelvic Nodal RT | ADT use and Duration |
Boost Dose
(Target) |
Platform
(CK, LINAC, Other Particle) |
Endpoint | Late Toxicity | Additional Information |
| Miralbel [29] | 2010 | 50 | 5—LR 12—IR 33—HR D’Amico |
72 | 64 Gy/32# | Some 56% |
66% 6 months |
10–16 Gy/2# (DIL) |
LINAC | 98% bcDFS | ≥Gr 3 GU 0% GI 10% ≥Gr 2 GU 12% GI 20% RTOG |
Pilot study |
| Oermann [30] | 2010 | 24 | 13—IR 11—HR NCCN |
9.3 (month average) | 50.4 Gy/28# | Unknown | 42% Unknown duration |
19.5 Gy/3# (prostate and SVs) |
CK | Not reported | No late GI or GU toxicities reported (limited follow-up) CTCAE |
Pilot study |
| Katz and Kang [31,32] | 2010 and 2014 |
45 in vHDRB cohort and 52 in SBRT monotherapy cohort |
HR NCCN |
vHDRB cohort 69 |
vHDRB cohort 45 Gy/25# |
vHDRB cohort Yes 100%—partial coverage using four-field box |
vHDRB cohort 62% Unknown duration |
18–21 Gy/3# (prostate and SVs) |
CK |
vHDRB cohort 89.5%—IR 77.7%—HR (3 year bFFS) 69% (6 year bcDFS) |
vHDRB cohort ≥Gr 3 GU 2.3% GI 0% Gr 2 GU 2.3% GI 13.3% RTOG |
Retrospective, 2010 data included larger numbers due to inclusion of intermediate-risk PC |
|
SBRT monotherapy cohort 48 |
SBRT monotherapy cohort 35–36.25 Gy/5# |
SBRT monotherapy cohort No |
SBRT monotherapy cohort 50% Unknown duration |
SBRT monotherapy cohort 6 year bcDFS—no difference between cohorts (p = 0.86) |
SBRT monotherapy cohort ≥Gr 3 GU 3.9% GI 0% Gr 2 GU 7.8% GI 0% RTOG |
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| Jabbari [33] and Anwar [34] |
2012 and 2016 |
48 |
14—IR 34—HR NCCN |
42.7 | 45–50 Gy/25# | Some (if risk >15%, Roach formula) |
88% 6 months |
19–21 Gy/2# (prostate and SVs) |
CK | 90% (5 year bNED) | ≥Gr 3 GU 2.1% GI 0% ≥Gr 2 GU 25% GI 0% CTCAE |
Pilot study |
| Khmelevsky [35,36] | 2012 and 2018 |
116 in vHDRB cohort and 173 in conventional cohort |
LR—HR NCCN |
vHDRB cohort 67.8 |
vHDRB cohort 44–46 Gy/22–23# |
Some (selected IR—HR) |
vHDRB cohort 95% 6 months |
28.0–28.8 Gy (radiobiological equivalent of gray)/3–8# | Protons |
vHDRB cohort 60% (5 year bcRFS) |
vHDRB cohort ≥Gr 3 GU 2.8% GI 0.9% Gr 2 GU 8.3% GI 10.2% RTOG |
Randomized |
|
Conventional cohort 71.6 |
Conventional cohort 68–72 Gy/34–36# |
Conventional cohort 95% 6 months |
Conventional cohort 61.9% (5 year bcRFS) |
Conventional cohort ≥Gr 3 GU 3.8% GI 1.3% Gr 2 GU 9.1% GI 34.8% RTOG |
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| Lin [37] | 2014 | 41 | 32—HR 9—very HR NCCN |
42 | 45 Gy/25# | Yes 100% |
92.7% 24 months |
21 Gy/3# (prostate and SVs) |
CK | 91.9% (4 year bFFS) |
≥Gr 3 GU 0% GI 0% Gr 2 GU 3–11% GI 0% CTCAE |
Pilot study |
| Koh [38] | 2014 | 8 in vHDRB cohort and 17 in SBRT monotherapy cohort |
vHDRB cohort HR D’Amico |
29.3 (entire cohort) |
vHDRB cohort 40 Gy/20# |
Unknown |
vHDRB cohort 87.5% Unknown duration |
18–24 Gy/3–5# (not reported) |
CK |
vHDRB cohort 50% bcPFS |
vHDRB cohort ≥Gr 3 GU 0% GI 12.5% Gr 2 GU 0% GI 0% RTOG |
Retrospective |
|
SBRT monotherapy cohort LR—HR D’Amico |
SBRT monotherapy cohort 32–37.5 Gy/4–5# |
SBRT monotherapy cohort 83.3% for IR 100% for HR Unknown duration |
SBRT monotherapy cohort 100% bcPFS for LR-IR 83.3% bcPFS for HR |
SBRT monotherapy cohort ≥Gr 3 GU 0% GI 0% Gr 2 GU 0% GI 0% RTOG |
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| Freeman [39] | 2015 | 160 treated with boost among the total of 2000 in the study | 819—LR 619—IR 172—HR 3—metastatic 130—unspecified NCCN |
24 | 45–50 Gy/25# | Unknown | Unknown | 19.5–21.75 Gy/3# (not reported) |
CK | 92%—entire cohort 87%—HR (2 year bcDFS) |
≥Gr 3 GU 0% GI 0.1% Gr 2 not reported Unknown reporting scale |
Prospective database, 92% of cohort were SBRT monotherapy patients |
| Mercado [40] and Paydar [41] |
2016 and 2017 |
108 | 4—LR 45—IR 59—HR D’Amico |
53 | 45–50.4 Gy/25–28# | No | 63.6% 6 months |
19.5 Gy/3# (prostate and proximal SVs) |
CK | 100%—IR 89.8%—HR (3 year bcPFS) |
≥Gr 3 GU 6% GI 1% Gr 2 GU 40% GI 12% CTCAE |
Retrospective |
| Pontoriero [42] | 2016 | 5 in vHDRB cohort and 21 in SBRT monotherapy cohort |
vHDRB cohort HR D’Amico |
21.5 (entire cohort) |
vHDRB cohort 46 Gy/23# |
Yes (100%) |
vHDRB cohort 100% 24 months |
19 Gy/2# (not reported) |
CK |
vHDRB cohort 80% bcPFS |
vHDRB cohort ≥Gr 2 GU 0% GI 0% CTCAE |
Pilot study |
|
SBRT monotherapy cohort LR—IR D’Amico |
SBRT monotherapy cohort 38 Gy/4# |
SBRT monotherapy cohort 15% 6 months, 46% 24 months |
SBRT monotherapy cohort 100% bcPFS |
SBRT monotherapy cohort ≥Gr 2 GU 4.8% GI 4.8% CTCAE |
||||||||
| Kim [15,43,44,45] | 2016 (Phak), 2017 (x2), and 2022 |
42 |
31—IR 11—HR NCCN |
84.2 | 45 Gy/25# | Some | No | 21 Gy/3# (prostate and SVs) |
CK | 100%—IR 77.8%—HR (8 year bFFS) |
≥Gr 3 GU 0% GI 0% Gr 2 GU 11.9% GI 14.3% RTOG |
Phase 1/2a |
| Pasquier/CKNO-PRO) [46,47] | 2017 and 2020 |
76 | IR D’Amico |
62 | 46 Gy/23# | No | No | 18 Gy/3# (prostate) |
CK (N = 60) LINAC (N = 16) |
87.4% (5 year bcRFS) | ≥Gr 3 GU 0% GI 3.9% Gr 2 GU 1.4% GI 9.3% CTCAE |
Phase 2, multicentre |
| Feng [48] | 2018 | 145 in vHDRB cohort and 200 in SBRT monotherapy cohort |
vHDRB cohort 5—LR 51—IR 89—HR D’Amico |
vHDRB cohort 24 |
vHDRB cohort 45–50.4 Gy/25–28# |
Unknown |
vHDRB cohort 70.3% Unknown duration |
19.5 Gy/3# (not reported) |
CK |
vHDRB cohort Not reported |
vHDRB cohort 7.60 ± 0.42 AUA symptom score at 1 year 5.5% late urinary flare |
Phase 1/2, 1 year AUA symptom scores significantly differed (p = 0.003) |
|
SBRT monotherapy cohort 75—LR 104—IR 21—HR D’Amico |
SBRT monotherapy cohort 24 |
SBRT monotherapy cohort 35–36.25 Gy/5# |
SBRT monotherapy cohort 12% Unknown duration |
SBRT monotherapy cohort Not reported |
SBRT monotherapy cohort 9.53 ± 0.47 AUA symptom score at 1 year 12% late urinary flare |
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| Alayed [49] | 2019 | 30 | IR NCCN |
72 | 37.5 Gy/15# | No | 3.3% <6 months |
10/12.5/15 Gy in single # (prostate and SVs) |
LINAC | 92.3% bcPFS | ≥Gr 3 GU 3.3% GI 3.3% ≥Gr 2 GU 43.3% GI 26.6% CTCAE |
Phase 1 study |
| Eade/BOOSTER [50] | 2019 | 36 | 13—IR 23—HR D’Amico |
24 | 46 Gy/23# | Some (if HR) |
61% 18 months |
20/22/24 Gy in 2# (prostate) 25/27.5/30 Gy in 2# (to DIL if Identified) |
LINAC | 93.3% (3 year bFFS) | ≥Gr 3 GU 0% GI 0% Gr 2 GU 19.3% GI 0% CTCAE |
Phase 1 study |
| Johansson [51] | 2019 | 504 | 94—LR 158—IR 135—HR 117—Very HR NCCN |
113 | 50 Gy/25# | Some 16%—HR 60%—very HR |
55% 17% LR 32% IR (5 months) 76% HR (9 months) 91% very HR (24 months) |
20 Gy/4# (prostate and SVs) |
Proton | 100%, 94%—LR 94%, 87%—IR 82%, 63%—HR 72%, 55%—very HR (5 and 10 year PSA relapse-free) |
≥Gr 3 GU 2% GI 0% (in pre-treatment symptom-free patients) Gr 2 not reported RTOG at 5 years |
Proton boost, retrospective |
| Pryor/PROMETHEUS [52] | 2019 | 135 | 103—IR 32—HR D’Amico |
24 | 46 Gy/23# or 36 Gy/12# | Some (8%) |
54% (36% <6 months and 18% >6 months) |
19–20 Gy/2# (prostate and SVs) |
LINAC | 98.6% (2 year bcPFS) |
≥Gr 3 GU 2.2% GI 2% Gr 2 GU 24.9% GI 4.5% CTCAE |
Phase 2, multicentre |
| Pollack/LEAD [53] | 2020 | 25 | IR—HR NCCN |
66 | 76 Gy/38# | Some (in HR, 56 Gy/38#) | 56% 6 months |
12–14 Gy/1# (MRI DIL) |
Proton | 92% bcPFS | ≥Gr 3 GU 4% GI 0% Gr 2 GU 16% GI 16% CTCAE |
Phase 1 using lattice extreme ablative dose technique |
| Wang [54] | 2020 | 121 in vHDRB cohort and 132 in conventional cohort |
HR—very HR NCCN |
vHDRB cohort 48.5 |
vHDRB cohort 45 Gy/25# WPRT |
Yes 100% |
vHDRB cohort 91.7% Mean: 24.6 months |
21 Gy/3# (prostate and SVs) | CK |
vHDRB cohort 93.9% (4 year bFFS) |
vHDRB cohort ≥Gr 3 GU 0.8% GI 1.7% Gr 2 GU 19.8% GI 1.7% CTCAE |
Retrospective |
|
Conventional cohort 41.4 |
Conventional cohort 74–79.2 Gy in 1.8–2 Gy/# |
Conventional cohort 97.7% Mean: 30.6 months |
Conventional cohort 89.1% (4 year bFFS) |
Conventional cohort ≥Gr 3 GU 2.3% GI 2.3% Gr 2 GU 15.9% GI 4.5% CTCAE |
||||||||
| Narang [55] | 2020 | 44 | 11—HR 22—very HR 9—node-positive 2—metastatic NCCN |
63.5 | 45 Gy to nodes, 50 Gy to prostate Boost involved nodes (54–56 Gy) All in 25# |
Yes 100% |
86.4% 3 months |
18 Gy/3# (prostate) 16 Gy/2# (to bone metastatic lesions) |
CK | 91.4% (5 year bcPFS) |
≥Gr 3 GU 4.5% GI 0% Gr 2 not reported CTCAE |
Phase 1/2 |
| Kim/ADEBAR [56] | 2020 | 26 | 1—HR 25—very HR NCCN |
35 | 44 Gy/20# | Yes 100% |
100% 25 months |
18—21 Gy/3# (prostate and SVs) |
CK | 88.1% (3 year bcRFS) |
≥Gr 3 GU 0% GI 0% Gr 2 GU 4% GI 4% CTCAE |
Phase 1/2 |
| Milecki/HYPO-PROST [57] | 2020 | 105 in vHDRB arm and 103 in conventional arm |
HR D’Amico |
60.1 |
vHDRB arm 46 Gy/23# |
Yes | Yes 24 months |
15 Gy/2# (prostate and SVs) |
LINAC |
vHDRB arm 78.2% (5 year bcRFS) |
vHDRB arm ≥Gr 2 GU 5.9% GI 13.9% RTOG |
Randomized, abstract only |
|
Conventional arm 76 Gy/38# |
Conventional arm 82.9% (5 year bcRFS) |
Conventional arm ≥Gr 2 GU 5.8% GI 8.6% RTOG |
||||||||||
| Turna [58] | 2021 | 34 | HR D’Amico |
41.2 | 50 Gy/25# WPRT | Yes 100% |
88.2% 36 months |
21 Gy/3# (prostate and proximal SVs) |
LINAC | 100% bcPFS | ≥Gr 3 GU 0% GI 0% Gr 2 GU 8% GI 17.6% CTCAE |
Retrospective |
| Chen [59] | 2021 | 130 in vHDRB cohort and 101 in HDR brachytherapy boost cohort |
38.2% IR 29% HR 32.8% very HR NCCN |
vHDRB cohort 73.4 |
45 Gy/25# | Some |
vHDRB cohort 96.2% 6 months |
vHDRB cohort 19–21 Gy/2# (prostate and SVs) |
CK |
vHDRB cohort 88.8%, 85.3% (5 and 10 year BCRF) |
vHDRB cohort ≥Gr 3 GU 4.6% GI 1.5% Gr 2 not reported RTOG |
Propensity score-matched analysis with HDR brachytherapy boost |
|
HDR brachytherapy cohort 186 |
HDR brachytherapy cohort 92.1% 6 months |
HDR brachytherapy cohort 19 Gy/2# |
HDR brachytherapy cohort 91.8%, 74.6% (5 and 10 year BCRF) |
HDR brachytherapy cohort ≥Gr 3 GU 3.0% GI 0% Gr 2 not reported RTOG |
||||||||
| Phuong [60] | 2022 | 2 treated with vHDRB boost among the total of 22 in the study | IR—HR NCCN |
32 | 41.25 Gy/15# | Yes 100% |
95% 4 months |
19 Gy/2# (vHDRB) 15 Gy/1# (HDR brachytherapy boost) (prostate and SVs) |
CK | 100% (3 year bcPFS) | ≥Gr 3 GU 0% GI 0% Gr 2 GU 14% GI 5% CTCAE |
Retrospective, mixed population with SBRT monotherapy |
| Novikov [61] | 2022 | 51 in vHDRB cohort and 98 in HDR brachytherapy cohort |
HR, very HR 29.4% of vHDRB cohort were node-positive 32.7% of HDR brachytherapy cohort were node-positive NCCN |
vHDRB cohort 55.1 |
45–50.4 Gy/25–28# Some used 3dcrt |
Yes 100% |
100% Unknown duration |
vHDRB cohort 21 Gy/3# (prostate and proximal SVs) |
LINAC |
vHDRB cohort 76.5%, 67.7% (3 and 5 year bcRFS) |
vHDRB cohort ≥Gr 3 GU 0% GI 5.9% Gr 2 GU 9.8% GI 8.6% CTCAE |
Retrospective, no rectal stabilization devices or hydrogel spacers used, significant Gr 3 and 4 toxicity in vHDRB cohort |
|
HDR brachytherapy cohort 87.7 |
HDR brachytherapy cohort 20 Gy/2# or 15 Gy/1# |
HDR brachytherapy cohort 74.6%, 66.8% (3 and 5 year bcRFS) |
HDR brachytherapy cohort ≥Gr 3 GU 1.1% GI 0% Gr 2 GU 28.6% GI 8.2% CTCAE |
Abbreviations: N, number of patients; ADT, androgen deprivation therapy; WPRT, whole pelvic radiotherapy; SV, seminal vesicle; CK, CyberKnife; LINAC, linear acceleration; LR, low risk; IR, intermediate risk; HR, high risk; GI, gastrointestinal; GU, genitourinary; SBRT, sterotactic body radiation therapy; HDR, high-dose-rate brachytherapy; DIL, dominant intraprostatic lesion; AUA, American Urological Association; bFFS, biochemical failure-free survival; bcPFS, biochemical progression-free survival; bcRFS, biochemical recurrence-free survival; bcDFS, biochemical disease-free survival; bNED, biochemical no evidence of disease; BCRF, biochemical recurrence freedom; RTOG/CTCAE indicate that the RTOG or Common Terminology Criteria for Adverse Events toxicity scales were used for reporting.