Appendix 1.
Outcomes and toxicities with different external-beam radiation therapy technologies and methods for prostate cancer treatment
| Study/author | Year accrued/era | Comparison/clinical question | Arms | N | Risk groups | Med FU (mo) | Outcomes | Toxicities | Conclusion(s) |
|---|---|---|---|---|---|---|---|---|---|
| Perez12 | 1992-1999 | Clinical retrospective comparison of 120 rotational arcs vs 3D-CRT | Standard RT, with 120° bilateral arcs, using portals with 2-cm margins: 68-70 Gy (no ADT) | 155 | L, I | 56 | ASTRO FFBFs: T1b/c: 61% vs 75% (SS) T2: 65% vs 79% (SS) |
Moderate dysuria: 2%-5% vs 6%-9% (SS) Late GI grade 2 morbidity: 7% vs 1% (SS) |
3D-CRT has improved FFBF and toxicity profile for T1-2 cancers |
| 3D-CRT: 68-74 Gy (no ADT) | 312 | 38 | |||||||
| MD Anderson/Kuban13, 14 | 1993-1998 | RCT of dose escalation of 3D-CRT | 3D-CRT: 78 Gy | 151 | L, I, H | 108 | Phoenix FFBF: 78% vs 59% L: 92% vs 73% I: 78% vs 76% H: 67% vs 33% |
Late RTOG grade 3-4 toxicities: GI 7% vs 1% (SS) GU 4% vs 1% (NS) |
Dose escalation to 78 Gy improves FFBF, CSS for I, H patients |
| 3D-CRT: 70 Gy | 150 | ||||||||
| RTOG 9406/Michalski15, 16 | 1994-2000 | Phase 1/2 RCT of dose escalation of 3D-CRT | Levels I-V (respective): 68.4, 73.8, 79.2 Gy, all at 1.8-Gy fractions; or 74 Gy and 78 Gy at 2-Gy fractions (±ADT) | 1,084 | L, I, H | 110-140 | Phoenix FFBFs (for levels I-V, respectively) L: 68%, 73%, 67%, 84%, 80%; I: 70%, 62%, 70%, 74%, 69% H: 42%, 62%, 68%, 54%, 67%. |
Increased GU/GI Grade ≥2 toxicity using 78 Gy vs 68.4 Gy to 79.2 Gy or 74 Gy (hazard ratios 1.6-2.6) | Improved outcomes with 78-79.2 Gy vs lower doses Increased toxicity with higher doses of 3D-CRT |
| Zelefsky17 | 1992-1998 | Clinical retrospective comparison of 3D-CRT vs IMRT | 3D-CRT: 72 Gy + 9-Gy boost | 61 | L, I, H | 12 | N/A | Combined rates of acute G1-2 GI toxicities and GI bleeding improved with IMRT (2% vs 10%, SS) | Improved dosimetry, toxicity, safe deliverable dose to target with IMRT vs 3D-CRT |
| IMRT: 81 Gy | 171 | N/A | |||||||
| Fox Chase/Pollack18 | 2002-2006 | RCT of HFRT with IMRT vs CFRT with IMRT to improve FFBF | CFRT: 76 Gy in 2-Gy fractions (±ADT) | 152 | L, I, H | 68 | 5-y Phoenix FFBF similar between the 2 arms (78% vs 77%) | Acute Grade ≥2 GI toxicities similar; Acute GU toxicities statistically higher with HFRT (18.3% vs 8.3%, SS); late toxicities similar | HFRT did not result in improved FFBF but was delivered in shorter time. Men with poor GU function before HFRT may not be ideal candidates for the approach. |
| HFRT: 70.2 Gy in 2.7-Gy fractions (±ADT) | 151 | ||||||||
| Sheets 201219 | 2000-2008 | SEER analysis of any late toxicity of protons vs IMRT, 3D-CRT | Proton | 684 | L, I, H | 46-50 | N/A | Absolute risk per 100 person-years: GU: 26 vs 25 (NS) GI: 25 vs 13 (SS) |
IMRT patients had a lower rate of GI morbidity (vs protons). |
| IMRT | 684 | N/A | |||||||
| 3D-CRT | 6,310 | L, I, H | N/A | Absolute risk per 100 person-years: GI diagnoses: 13.4 vs 14.7 (SS) Hip fracture: 0.8 vs 1.0 (SS) |
IMRT patients had lower rate of diagnosis of GI morbidity and hip fracture (vs 3D-CRT). | ||||
| IMRT | 6,666 | N/A | |||||||
| Zelefsky20 | 2006-2009 | Retrospective cohort study of IMRT vs IMRT with IGRT | IMRT to 86.4 Gy | 190 | L, I, H | 34 | No differences in 3-y FFBF (88% to 94%) for L or I patients FFBF improved for H patients (97% vs 78%, SS) with IGRT |
3-y Grade ≥2 GU toxicity: 20% vs 10.4%, respectively (SS) 3-y Grade ≥2 GI toxicity similar: 1.0 vs 1.6%, respectively (NS) |
IGRT, with fiducial markers, is associated with improved FFBF among high-risk patients and a lower rate of late GU toxicity compared with high-dose IMRT. |
| + IGRT kV imaging of implanted prostatic fiducial markers | 186 | ||||||||
| Katz21, 22, 23 | 2006-2009 | Phase 1/2 dose-escalation study of robotic-arm SBRT | Robotic-arm SBRT: 35-36.25 Gy in 5 fractions | 515 | L, I > H | 40 | 5-y Phoenix FFBFs: L: 98%, I: 93%, H: 75% |
RTOG late grade 3-4 toxicity: 0% | SBRT has promising rates of toxicity and efficacy. |
ADT, androgen deprivation therapy; ASTRO, American Society for Radiation Oncology; 3D-CRT, 3-dimensional conformal radiation therapy; CFRT, conventionally fractionated radiation therapy (ie, 1.8-2.0 Gy/fraction); CSS, cancer-specific survival; FFBF, freedom from biochemical failure; FU, follow-up; GI, gastrointestinal; GU, genitourinary; H, high risk; HFRT, hypofractionated radiation therapy (ie, 2.1-3.5 Gy/fraction); I, intermediate risk; IGRT, image guided radiation therapy; IMRT, intensity modulated radiation therapy; L, low risk; N/A, not applicable; NR, not reported; NS, not significant; OS, overall survival; RCT, randomized controlled trial; RTOG, Radiation Therapy Oncology Group; SBRT, stereotactic body radiation therapy (ie, >3.5 Gy/fraction in 5 fractions or less); SEER, Surveillance, Epidemiology, and End Results; SS, statistically significant.
Note: ASTRO: 3 consecutive PSA (prostate-specific antigen) rises; Phoenix: PSA nadir + 2 ng/mL.