Current Knowledge on Radiation-Therapy-Induced Erectile Dysfunction in Prostate-Cancer Patients: A Narrative Review
Abstract
:1. Introduction
2. Radiation-Therapy-Induced Erectile Dysfunction Pathophysiology
3. Radiation Therapy Options in PCa Patients and Associated RI-ED Rates
3.1. External Beam Radiation Therapy
3.2. Hypofractionated Radiation Therapy
3.3. Proton-Beam Therapy
Name/Author | Year | Country | Study Design | F/U | Participants Number | Therapeutic Option | Results |
---|---|---|---|---|---|---|---|
Hall et al. [28] NRG/RTOG 0125 trial | 2022 | USA | Prospective Phase III RCT | 24 months | 1532 | EBRT | ED occurrence |
769 | 70.2 Gy in 39 fractions | 38.1% | |||||
763 | 79.2 Gy in 44 fractions | 49.7% | |||||
p = 0.051 | |||||||
Donovan et al. [29] ProtecT trial | 2016 | UK | Comparative trial | 6 years | ED occurrence/worsening | ||
545 | AS | 15% | |||||
553 | RP | 55% | |||||
545 | EBRT | 45% | |||||
Dearnaley et al. [31] CHHiP trial | 2016 | UK, Ireland, Switzerland, New Zealand | International multicenter phase III RCT | 5 years | 3216 | EBRT | Sexual symptoms ≥2 |
LENT-SOMA scale | |||||||
1065 | CF 74 Gy | 67% | |||||
1074 | HFX 60 Gy | 65% | |||||
1077 | HFX 57 Gy | 64% | |||||
Lee et al. [33] NRG Oncology RTOG0415 | 2016 | USA | Randomized Phase III noninferiority comparing study | 5.8 years | 1092 | EBRT | GU toxicity, early and late |
542 | CF 73.8 Gy | 61.6%, 52.3% | |||||
550 | HFX 60 Gy | 62.2%, 58.1% | |||||
Catton et al. [34] PROFIT trial | 2017 | Canada, | Noninferiority RCT | 6 years | 1206 | EBRT | Late ≥ 3 GU toxicity |
Australia, | 608 | HFX 60 Gy | 2.1% | ||||
France | 598 | CF 78 Gy | 3.0% | ||||
Rasmusson et al. [36] HYPO-RT-PC trial | 2020 | Sweden | Open-lab Phase III RCT | 5 years | 673 | EBRT | ED occurrence |
330 | CF | 27% | |||||
343 | UHF | 27% | |||||
Pepe et al. [42] | 2022 | Italy | Experimental trial | 18 months | 56 | Hydrogel injection SpaceOAR before HFX 60 Gy | EF preservation 62.5% |
Brand et al. [45] PACE-B trial | 2022 | UK, | Open-label, multicohort, randomized, controlled, Phase III trial | 2 years | RTOG grade ≥2 GU toxicity | ||
Ireland, | 430 | CF 78 Gy | 2% | ||||
Canada | 414 | SBRT 36 Gy | 13% | ||||
Ho et al. [46] | 2018 | USA | Observational trial | 5 years | 254 | PBT | Ability to function sexuality loss (EPIC) |
1 year F/U 24% | |||||||
3 year F/U 82% | |||||||
5 year F/U 54% |
4. Sexual Rehabilitation in RI-ED Patients
4.1. Phosphodiesterase Type 5 Inhibitors
4.2. Vasoactive Injectables, Vacuum Therapy, and Pelvic-Floor Physiotherapy
4.3. Regenerative Therapies and Future Directions
Name/Author | Year | Country | Study Design | Participants Number | Therapeutic Option | Dosing Schedule | Interval from RT | Outcomes |
---|---|---|---|---|---|---|---|---|
S. Kedia et al. [34] | 1999 | USA | Prospective observational trial | 21 | Sildenafil | 50 mg with a titration to 100 mg if needed; 1 sildenafil tablet approximately 1 h before sexual activity | 24.6 +/− 5.8 months | Mean duration of vaginal intercourse (CCEF), 12.7 ± 2.5 min; mean frequency of penetration score (IIEF 5), from 1.3 to 4.0; maintenance of erection score (IIEF 5), from 1.1 to 3.9. |
Weber DC. et al. [35] | 1999 | Switzerland | Prospective observational trial | 35 | Sildenafil | 100 mg orally once a week for 6 consecutive weeks | 18.5 months | Response rate, from 40% during the first week to 77% at 6 weeks; mean weekly IIEF 5 score of 13.8, 16.0, 17.0, 16.8, 17.0, and 17.6 at weeks 1 to 6, respectively. |
Zelefky MJ et al. [36] | 1999 | USA | Prospective observational trial | 50 | Sildenafil | Patients were initially given 50 mg of sildenafil and instructed to use the medication on at least three occasions | 19 months | Erection firmness improvement: significant in 74%, partial in 4%, no response in 22%; erection durability improvement: significant in 66%, partial in 6%, no improvement in 28%; libido improvement: in 18%. |
Watkins Bruner et al. [39] | 2013 | USA | Randomized, double-blinded, placebo-controlled crossover trial | 115 | Sildenafil | 12 weeks of sildenafil or placebo, followed by 1 week of no treatment, 12 weeks of a alternative flexible dosing schedule starting with a 50 mg dose (1 pill) 1 h prior to desired sexual activity and increasing up to 100 mg (2 pills) daily as needed. | 12 months (range 5.5–48) | 66%, any response; 10%, both placebo and sildenafil response; 21%, only sildenafil response; 3%, only placebo response. |
Ilic D. et al. [40] | 2012 | Australia | Randomized, double-blinded, placebo-controlled trial | 27 | Sildenafil | Standard 50 mg sildenafil tablets, one tablet each night. Patients were reviewed after 1 month, and if no adverse effects had been noted, they were instructed to take 2 tablets each evening. Six-month trial period. | 1 month | Based on IIEF-5 measure, sildenafil vs. placebo: Baseline: 24 both; 4 weeks: 24–21; 12 weeks: 24–20; 2 years: 19–20. |
Pisansky et al. [41] Therapy Oncology Group [0831] | 2014 | USA Canada | Stratified, placebo-controlled, double-blind, parallel-group study with 1:1 randomization. | 242 | Tadalafil | 5 mg for 24 consecutive weeks | 1 week after RT initiation | EEF5-based EF. Tadalafil vs. placebo. Baseline, 24.8–25.1; 30 weeks, 20.7–20.9; 50 weeks, 21.2–20.4. |
Incrocci et al. [42] | 2006 | Netherland | Randomized, double-blind, placebo controlled, cross-over-study | 358 | Tadalafil | 20 mg on demand tadalafil or placebo for 6 weeks. | 12 months | Erectile function, IIEF score: Baseline, 8.4; after tadalafil, 17.7; after placebo, 9.5. Erectile function, SEP diary, tadalafil vs. placebo: Question 1: 64–30; Question 2: 47–19; Question 3: 46–12; Question 4: 43–7; Question 5: 48–15. |
Ricardi et al. [43] | 2010 | Italy | Randomized comparative study | 52 | Tadalafil | On-demand 20 mg or once-a-day 5 mg tadalafil for 12 weeks | 6 months | IIEF-based EF. On-demand 20 mg vs. once-a-day 5 mg: Baseline: 6–6; 1 month: 22–24; 3 months: 25–27. |
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Labate, C.; Panunzio, A.; De Carlo, F.; Zacheo, F.; De Matteis, S.; Barba, M.C.; Carbonara, U.; Rizzo, F.L.; Leo, S.; Forte, S.; et al. Current Knowledge on Radiation-Therapy-Induced Erectile Dysfunction in Prostate-Cancer Patients: A Narrative Review. Uro 2023, 3, 104-116. https://doi.org/10.3390/uro3020013
Labate C, Panunzio A, De Carlo F, Zacheo F, De Matteis S, Barba MC, Carbonara U, Rizzo FL, Leo S, Forte S, et al. Current Knowledge on Radiation-Therapy-Induced Erectile Dysfunction in Prostate-Cancer Patients: A Narrative Review. Uro. 2023; 3(2):104-116. https://doi.org/10.3390/uro3020013
Chicago/Turabian StyleLabate, Connie, Andrea Panunzio, Francesco De Carlo, Federico Zacheo, Sara De Matteis, Maria Cristina Barba, Umberto Carbonara, Floriana Luigina Rizzo, Silvana Leo, Saverio Forte, and et al. 2023. "Current Knowledge on Radiation-Therapy-Induced Erectile Dysfunction in Prostate-Cancer Patients: A Narrative Review" Uro 3, no. 2: 104-116. https://doi.org/10.3390/uro3020013