Postoperative Radiotherapy of Prostate Cancer: Adjuvant versus Early Salvage
Abstract
:1. Introduction
2. Methods
3. Results
4. Discussion
4.1. Follow-Up Time Not Sufficient to Conclude on Oncological Outcome
4.2. Immortal Time Bias
4.3. High-Risk Subgroup Underpowered
4.4. Impact of ADT on Trial Results
4.5. Toxicity Possibly Just Delayed
4.6. RT Technique (IMRT vs. 3DRT) Might Have Influenced Outcomes
4.7. Heterogeneity and Inconsistencies in Radiation Dose and Target Volume Definition among the Three RCTs in the Meta-Analysis
4.8. Radiation Dose and Fractionation Not Considered Evidence-Based Standard of Care
4.9. ART Was Performed within Less Than 6 Months after Surgery
4.10. Potential Inclusion of Patients with Persisting PSA after RP
4.11. Risk of Delayed Referral to SRT
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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RADICALS-RT | GETUG-AFU 17 | RAVES | ARTISTIC Meta-Analysis | |
---|---|---|---|---|
Trial design | Superiority (two-sided, 80% power to detect increase from 90% to 95% 10-year FFDM, α = 5%) | Superiority of ART (one-sided, 80% power to detect increase of 10% 5-year EFS for ART over SRT, α = 5%) | Non-inferiority of SRT (one-sided, 80% power to detect 5-year FFbP difference of <10% for SRT, α = 5%) | Superiority (two-sided, 90% power to detect a 5% difference in 5-year EFS, 99% power to detect 10% difference) |
Primary Outcome | FFDM | EFS | FFbP | EFS |
Accrual period | 2007–2016 | 2008–2016 | 2009–2015 | |
Planned accrual (n) | 2600 | 718 | 470 | (>120 events per group) |
Actual inclusion (n, %) | 1396 (53.7%) | 424 (59.1%) | 333 (70.9%) | 2153 (events: 138 SRT, 126 ART) |
Main inclusion criteria | One or more of: pT3/pT4, R+, Gleason Score 7–10, PSA > 10 ng/mL (including pT2) | pT3/pT4a and R+ | pT3/4 or R+ (including pT2) | |
RT dose for ART and eSRT | 66 Gy in 33 Fx both groups (61%) or 52.5 Gy in 20 Fx (29%) | 66 Gy in 33 Fx both groups (lymph nodes median 46 Gy) | 64 Gy in 32 Fx both groups | |
RT field | Prostate bed, additionally pelvic lymph nodes in 7% of ART arm and 3 % of SRT arm | Prostate bed, additionally pelvic lymph nodes in 18% of ART arm and 24 % of SRT arm | Prostate bed | |
ADT | Randomized to 6 or 24 months of LHRH- analogue or Bicalutamid (RADICALS-HT double randomization) or as clinically indicated for 24% of ART arm and 27% of SRT arm. | All patients: 6 months of triptoreline | none | |
ART timing | ≤6 months after RP | ≤6 months after RP | ≤6 months after RP | |
Trigger for eSRT | PSA > 0.1 ng/mL and rising or 3 × consecutive rising below 0.1 ng/mL | PSA > 0.2 ng/mL | PSA > 0.2 ng/mL | |
eSRT timing | ≤2 months of trigger PSA | ASAP after trigger PSA, before PSA of 1 ng/mL | ≤4 months of trigger PSA | |
Number of patients who received SRT | 228/699 (32.6%) | 115/212 (54.2%) | 84/167 (50.3%) | 421/1078 (39.1%) * |
Median follow-up (months) | 60 | 75 | 78 | 60–78 months |
Main result (ART vs. eSRT) | 5-year FFbP: 85% vs. 88% | 5-year EFS: 92% vs. 90% | 5-year FFbP: 86% vs. 87%. | 5-year EFS: 89% vs. 88% |
GU toxicity (ART vs. eSRT) | G3+: 9% (54/599) vs. 5.1% (32/621) # | G2+: 59% (125/212) vs. 22% (46/212) | G2+: 70% (116/166) vs. 54% (90/167) | |
GI toxicity (ART vs. eSRT) | G3+: 2% (12/599) vs. 0.5% (3/621) ## | G2+: 8% (17/212) vs. 5% (11/212) | G2+: 14% (24/116) vs. 10% (16/167) | |
% of IMRT (ART vs. eSRT) | 30% vs. 47% |
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Wegener, D.; Aebersold, D.M.; Grimm, M.-O.; Hammerer, P.; Froehner, M.; Graefen, M.; Boehmer, D.; Zips, D.; Wiegel, T. Postoperative Radiotherapy of Prostate Cancer: Adjuvant versus Early Salvage. Biomedicines 2022, 10, 2256. https://doi.org/10.3390/biomedicines10092256
Wegener D, Aebersold DM, Grimm M-O, Hammerer P, Froehner M, Graefen M, Boehmer D, Zips D, Wiegel T. Postoperative Radiotherapy of Prostate Cancer: Adjuvant versus Early Salvage. Biomedicines. 2022; 10(9):2256. https://doi.org/10.3390/biomedicines10092256
Chicago/Turabian StyleWegener, Daniel, Daniel M. Aebersold, Marc-Oliver Grimm, Peter Hammerer, Michael Froehner, Markus Graefen, Dirk Boehmer, Daniel Zips, and Thomas Wiegel. 2022. "Postoperative Radiotherapy of Prostate Cancer: Adjuvant versus Early Salvage" Biomedicines 10, no. 9: 2256. https://doi.org/10.3390/biomedicines10092256
APA StyleWegener, D., Aebersold, D. M., Grimm, M. -O., Hammerer, P., Froehner, M., Graefen, M., Boehmer, D., Zips, D., & Wiegel, T. (2022). Postoperative Radiotherapy of Prostate Cancer: Adjuvant versus Early Salvage. Biomedicines, 10(9), 2256. https://doi.org/10.3390/biomedicines10092256