Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec 13:13:1281432.
doi: 10.3389/fonc.2023.1281432. eCollection 2023.

Unraveling the safety of adjuvant radiotherapy in prostate cancer: impact of older age and hypofractionated regimens on acute and late toxicity - a multicenter comprehensive analysis

Milly Buwenge #  1 , Gabriella Macchia #  2 , Letizia Cavallini  1   3 , Annalisa Cortesi  4 , Claudio Malizia  5 , Lorenzo Bianchi  1   6 , Maria Ntreta  3 , Alessandra Arcelli  3 , Ilaria Capocaccia  1   3 , Elena Natoli  1   3 , Savino Cilla  7 , Francesco Cellini  8   9 , Luca Tagliaferri  8 , Lidia Strigari  10 , Silvia Cammelli  1   3 , Riccardo Schiavina  1   6 , Eugenio Brunocilla  1   6 , Alessio Giuseppe Morganti #  1   3 , Francesco Deodato #  2   9
Affiliations

Unraveling the safety of adjuvant radiotherapy in prostate cancer: impact of older age and hypofractionated regimens on acute and late toxicity - a multicenter comprehensive analysis

Milly Buwenge et al. Front Oncol. .

Abstract

Background: The objective of this study was to assess the impact of age and other patient and treatment characteristics on toxicity in prostate cancer patients receiving adjuvant radiotherapy (RT).

Materials and methods: This observational study (ICAROS-1) evaluated both acute (RTOG) and late (RTOG/EORTC) toxicity. Patient- (age; Charlson's comorbidity index) and treatment-related characteristics (nodal irradiation; previous TURP; use, type, and duration of ADT, RT fractionation and technique, image-guidance systems, EQD2 delivered to the prostate bed and pelvic nodes) were recorded and analyzed.

Results: A total of 381 patients were enrolled. The median EQD2 to the prostate bed (α/β=1.5) was 71.4 Gy. The majority of patients (75.4%) were treated with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Acute G3 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 0.5% and 1.3%, respectively. No patients experienced >G3 acute toxicity. The multivariable analysis of acute toxicity (binomial logistic regression) showed a statistically significant association between older age (> 65) and decreased odds of G≥2 GI acute toxicity (OR: 0.569; 95%CI: 0.329-0.973; p: 0.040) and decreased odds of G≥2 GU acute toxicity (OR: 0.956; 95%CI: 0.918-0.996; p: 0.031). The 5-year late toxicity-free survival rates for G≥3 GI and GU toxicity were 98.1% and 94.5%, respectively. The only significant correlation found (Cox's regression model) was a reduced risk of late GI toxicity in patients undergoing hypofractionation (HR: 0.38; 95% CI: 0.18-0.78; p: 0.008).

Conclusions: The unexpected results of this analysis could be explained by a "response shift bias" concerning the protective effect of older age and by treatment in later periods (using IMRT/VMAT) concerning the favorable effect of hypofractionation. However, overall, the study suggests that age should not be a reason to avoid adjuvant RT and that the latter is well-tolerated even with moderately hypofractionated regimens.

Keywords: adjuvant therapy; observational study; predictive factors; prostate neoplasms; radiotherapy; toxicity.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin (2018) 68(6):394–424. doi: 10.3322/caac.21492 - DOI - PubMed
    1. Thompson IM, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, et al. . Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA (2006) 296(19):2329–35. doi: 10.1001/jama.296.19.2329 - DOI - PubMed
    1. Wiegel T, Bottke D, Steiner U, Siegmann A, Golz R, Störkel S, et al. . Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol (2009) 27(18):2924–30. doi: 10.1200/JCO.2008.18.9563 - DOI - PubMed
    1. Bolla M, van Poppel H, Tombal B, Vekemans K, Da Pozzo L, de Reijke TM, et al. . Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet (2012) 380(9858):2018–27. doi: 10.1016/S0140-6736(12)61253-7 - DOI - PubMed
    1. Hackman G, Taari K, Tammela TL, Matikainen M, Kouri M, Joensuu T, et al. . Randomised trial of adjuvant radiotherapy following radical prostatectomy versus radical prostatectomy alone in prostate cancer patients with positive margins or extracapsular extension. Eur Urol (2019) 76(5):586–95. doi: 10.1016/j.eururo.2019.07.001 - DOI - PubMed

LinkOut - more resources