Patient-reported long-term sexual morbidity in prostate cancer survivors treated with external beam radiation therapy alone or combined with high-dose-rate brachytherapy
DOI:
https://doi.org/10.2340/sju.v60.42165Keywords:
HDR-brachytherapy, long-term sexual function, EPIC-26, quality of life, patient-reported sexual outcomesAbstract
Background: Prostate cancer can be treated with external beam radiation therapy (EBRT) alone or combined with high-dose-rate brachytherapy (HDR-BT+), usually with additional hormonal treatment (HT).
The aim of this long-term cross-sectional study was to compare patient-reported sexual function, hormonal symptoms and quality of life (QoL) after EBRT-only or HDR-BT+.
Methods: In 2016, minimum 5 years after treatment, men treated with HDR-BT+ (n = 248) or EBRT-only (n = 91) responded to a questionnaire containing the Expanded Prostate Cancer Index Composite (EPIC)-26 and the Short Form-12 (SF-12).
Results: Median age at time of answering the questionnaire was 74 years (range 54–86). The majority in the HDR-BT+ group received HT for ≥ 2 years compared to 1/3rd in the EBRT-only group. In crude analyses, the sexual domain summary score (DSS) was significantly higher in the HDR-BT+ compared to the EBRT-only group (32.3 vs. 24.1). All sexual items were significantly better in the HDR-BT+ group except sexual problem. Significantly less fatigue was seen in the HDR-BT+ group despite longer duration of HT. Physical and mental health were similar in both groups.
When adjusted for possible confounders, the differences between treatment groups were no longer statistically significant. Only age was significantly associated with lower sexual scores. Low hormonal DSS was significantly associated with decreased QoL.
Conclusion: Patients treated with HDR-BT+ had not worse long-term sexual function than men treated with EBRT-only. However, this difference disappeared when adjusted for possible confounders. Thus, the interplay of age, HT and fatigue indicates a strong impact on both QoL and sexual function.
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Warde P, Mason M, Ding K, et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet (London, England). 2011;378(9809):2104–2111. https://doi.org/10.1016/S0140-6736(11)61095-7 DOI: https://doi.org/10.1016/S0140-6736(11)61095-7
Bolla M, Gonzalez D, Warde P, et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med. 1997;337(5):295–300. https://doi.org/10.1056/NEJM199707313370502 DOI: https://doi.org/10.1056/NEJM199707313370502
Wedde TB, Smaastuen MC, Brabrand S, et al. Ten-year survival after High-dose-rate brachytherapy combined with external beam radiation therapy in high-risk prostate cancer: a comparison with the Norwegian SPCG-7 cohort. Radiother Oncol J Eur Soc Therap Radiol Oncol. 2018;132:211–217. https://doi.org/10.1016/j.radonc.2018.10.013 DOI: https://doi.org/10.1016/j.radonc.2018.10.013
Nguyen PL, Alibhai SM, Basaria S, et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015;67(5):825–836. https://doi.org/10.1016/j.eururo.2014.07.010 DOI: https://doi.org/10.1016/j.eururo.2014.07.010
Nabid A, Carrier N, Martin AG, et al. Duration of androgen deprivation therapy in high-risk prostate cancer: a randomized phase III trial. Eur Urol. 2018;74(4):432–441. https://doi.org/10.1016/j.eururo.2018.06.018 DOI: https://doi.org/10.1016/j.eururo.2018.06.018
Bolla M, de Reijke TM, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med. 2009;360(24):2516–2527. https://doi.org/10.1056/NEJMoa0810095 DOI: https://doi.org/10.1056/NEJMoa0810095
Heidenreich A, Aus G, Bolla M, et al. EAU guidelines on prostate cancer. Eur Urol. 2008;53(1):68–80. https://doi.org/10.1016/j.eururo.2007.09.002 DOI: https://doi.org/10.1016/j.eururo.2007.09.002
Aus G, Abbou CC, Bolla M, et al. EAU guidelines on prostate cancer. Eur Urol. 2005;48(4):546–551. https://doi.org/10.1016/j.eururo.2005.06.001 DOI: https://doi.org/10.1016/j.eururo.2005.06.001
Borghede G, Hedelin H, Holmang S, et al. Combined treatment with temporary short-term high dose rate iridium-192 brachytherapy and external beam radiotherapy for irradiation of localized prostatic carcinoma. Radiother Oncol J Eur Soc Therap Radiol Oncol. 1997;44(3):237–244. https://doi.org/10.1016/S0167-8140(97)00121-7 DOI: https://doi.org/10.1016/S0167-8140(97)00121-7
Lilleby W, Tafjord G, Raabe NK. Implementation of high-dose-rate brachytherapy and androgen deprivation in patients with prostate cancer. Int J Radiat Oncol Biol Phys. 2012;83(3):933–939. https://doi.org/10.1016/j.ijrobp.2011.08.028 DOI: https://doi.org/10.1016/j.ijrobp.2011.08.028
Michigan M. Expanded prostate cancer index composite, Michigan Medicine urology [Internet]. Available from: https://medicine.umich.edu/dept/urology/research/epic 2020 [cited 20.01.24]
Ware J Jr., Kosinski M, Keller SD. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996;34(3):220–233. https://doi.org/10.1097/00005650-199603000-00003 DOI: https://doi.org/10.1097/00005650-199603000-00003
Steinsvik EA, Axcrona K, Dahl AA, et al. Can sexual bother after radical prostatectomy be predicted preoperatively? Findings from a prospective national study of the relation between sexual function, activity and bother. BJU Int. 2012;109(9):1366–1374. https://doi.org/10.1111/j.1464-410X.2011.10598.x DOI: https://doi.org/10.1111/j.1464-410X.2011.10598.x
Fosså SD, Storås AH, Steinsvik EA, et al. Psychometric testing of the Norwegian version of the Expanded Prostate Cancer Index Composite 26-item version (EPIC-26). Scand J Urol. 2016;50(4):280–285. https://doi.org/10.3109/21681805.2016.1163617 DOI: https://doi.org/10.3109/21681805.2016.1163617
Gandek B, Ware JE, Aaronson NK, et al. Cross-validation of item selection and scoring for the SF-12 Health Survey in nine countries: results from the IQOLA Project. International Quality of Life Assessment. J Clin Epidemiol. 1998;51(11):1171–1178. https://doi.org/10.1016/S0895-4356(98)00109-7 DOI: https://doi.org/10.1016/S0895-4356(98)00109-7
Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998;16(1):139–144. https://doi.org/10.1200/JCO.1998.16.1.139 DOI: https://doi.org/10.1200/JCO.1998.16.1.139
Skolarus TA, Dunn RL, Sanda MG, et al. Minimally important difference for the Expanded Prostate Cancer Index Composite Short Form. Urology. 2015;85(1):101–105. https://doi.org/10.1016/j.urology.2014.08.044 DOI: https://doi.org/10.1016/j.urology.2014.08.044
SPSS. IBM, Chicago, Illinois, USA SPSS statistics. 2022.
EAU. EAU guidelines. Edn presented at the EAU Annual Cogress Amsterdam 2020. Elsevier, Amsterdam, The Netherlands 2020.
Widmark A, Klepp O, Solberg A, et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet (London, England). 2009;373(9660):301–308. https://doi.org/10.1016/S0140-6736(08)61815-2 DOI: https://doi.org/10.1016/S0140-6736(08)61815-2
Blanchard P, Davis JW, Frank SJ, et al. Quality of life after brachytherapy or bilateral nerve-sparing robot-assisted radical prostatectomy for prostate cancer: a prospective cohort. BJU Int. 2018;121(4):540–548. https://doi.org/10.1111/bju.14021 DOI: https://doi.org/10.1111/bju.14021
Widmark A, Gunnlaugsson A, Beckman L, et al. Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet (London, England). 2019;394(10196):385–395. https://doi.org/10.1016/S0140-6736(19)31131-6 DOI: https://doi.org/10.1016/S0140-6736(19)31131-6
Tree AC, Ostler P, van der Voet H, et al. Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2022;23(10):1308–1320. https://doi.org/10.1016/S1470-2045(22)00517-4 DOI: https://doi.org/10.1016/S1470-2045(22)00517-4
Wedde TB, Smaastuen MC, Vatne K, et al. External beam radiotherapy of prostate cancer with or without high dose-rate brachytherapy: the Norwegian experience with long-term urinary and bowel adverse effects. Scand J Urol. 2023;58:68–75. https://doi.org/10.2340/sju.v58.9571 DOI: https://doi.org/10.2340/sju.v58.9571
Spratt DE, Malone S, Roy S, et al. Prostate radiotherapy with adjuvant androgen deprivation therapy (ADT) improves metastasis-free survival compared to neoadjuvant ADT: an individual patient meta-analysis. J Clin Oncol. 2021;39(2):136–144. https://doi.org/10.1200/JCO.20.02438 DOI: https://doi.org/10.1200/JCO.20.02438
Kishan AU, Steigler A, Denham JW, et al. Interplay between duration of androgen deprivation therapy and external beam radiotherapy with or without a brachytherapy boost for optimal treatment of high-risk prostate cancer: a patient-level data analysis of 3 cohorts. JAMA Oncol. 2022;8(3):e216871. https://doi.org/10.1001/jamaoncol.2021.6871 DOI: https://doi.org/10.1001/jamaoncol.2021.6871
Yorozu A, Namiki M, Saito S, et al. Trimodality therapy with iodine-125 brachytherapy, external beam radiation therapy, and short- or long-term androgen deprivation therapy for high-risk localized prostate cancer: results of a multicenter, randomized phase 3 trial (TRIP/TRIGU0907). Int J Radiat Oncol Biol Phys. 2024;118(2):390–401. https://doi.org/10.1016/j.ijrobp.2023.08.046 DOI: https://doi.org/10.1016/j.ijrobp.2023.08.046
Kikkawa K, Iba A, Kohjimoto Y, et al. Impact of age on quality of life in patients with localized prostate cancer treated with high-dose rate brachytherapy combined with external beam radiotherapy. Int J Urol. 2018;25(4):366–371. https://doi.org/10.1111/iju.13530 DOI: https://doi.org/10.1111/iju.13530
Pompe RS, Karakiewicz PI, Zaffuto E, et al. External beam radiotherapy affects serum testosterone in patients with localized prostate cancer. J Sex Med. 2017;14(7):876–882. https://doi.org/10.1016/j.jsxm.2017.04.675 DOI: https://doi.org/10.1016/j.jsxm.2017.04.675
Delgado J, Ory J, Loloi J, et al. Persistent testosterone suppression after cessation of androgen deprivation therapy for prostate cancer. Cureus. 2022;14(12):e32699. https://doi.org/10.7759/cureus.32699 DOI: https://doi.org/10.7759/cureus.32699
Farhood B, Mortezaee K, Haghi-Aminjan H, et al. A systematic review of radiation-induced testicular toxicities following radiotherapy for prostate cancer. J Cell Physiol. 2019;234(9):14828–14837. https://doi.org/10.1002/jcp.28283 DOI: https://doi.org/10.1002/jcp.28283
Rasmusson E, Gunnlaugsson A, Wieslander E, et al. Erectile dysfunction and absorbed dose to penile base structures in a randomized trial comparing ultrahypofractionated and conventionally fractionated radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2020;107(1):143–151. https://doi.org/10.1016/j.ijrobp.2020.01.022 DOI: https://doi.org/10.1016/j.ijrobp.2020.01.022
van der Wielen GJ, Hoogeman MS, et al. Dose-volume parameters of the corpora cavernosa do not correlate with erectile dysfunction after external beam radiotherapy for prostate cancer: results from a dose-escalation trial. Int J Radiat Oncol Biol Phys. 2008;71(3):795–800. https://doi.org/10.1016/j.ijrobp.2007.10.052 DOI: https://doi.org/10.1016/j.ijrobp.2007.10.052
Tøndel H, Lund J, Lydersen S, et al. Dose to penile bulb is not associated with erectile dysfunction 18 months post radiotherapy: a secondary analysis of a randomized trial. Clin Transl Radiat Oncol. 2018;13:50–56. https://doi.org/10.1016/j.ctro.2018.09.006 DOI: https://doi.org/10.1016/j.ctro.2018.09.006
Gay HA, Barthold HJ, O’Meara E, et al. Pelvic normal tissue contouring guidelines for radiation therapy: a Radiation Therapy Oncology Group consensus panel atlas. Int J Radiat Oncol Biol Phys. 2012;83(3):e353–e362. https://doi.org/10.1016/j.ijrobp.2012.01.023 DOI: https://doi.org/10.1016/j.ijrobp.2012.01.023
Helgason AR, Adolfsson J, Dickman P, et al. Sexual desire, erection, orgasm and ejaculatory functions and their importance to elderly Swedish men: a population-based study. Age Ageing. 1996;25(4):285–291. https://doi.org/10.1093/ageing/25.4.285 DOI: https://doi.org/10.1093/ageing/25.4.285
Lane A, Metcalfe C, Young GJ, et al. Patient-reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: study design, and baseline urinary, bowel and sexual function and quality of life. BJU Int. 2016;118(6):869–879. https://doi.org/10.1111/bju.13582 DOI: https://doi.org/10.1111/bju.13582
Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med. 2008;358(12):1250–1261. https://doi.org/10.1056/NEJMoa074311 DOI: https://doi.org/10.1056/NEJMoa074311
Dickinson K, Kupzyk K, Saligan L. Evaluating dimensions of fatigue in men with prostate cancer receiving radiation therapy. Cancer Nurs. 2021;44(1):71–78. https://doi.org/10.1097/NCC.0000000000000782 DOI: https://doi.org/10.1097/NCC.0000000000000782
Lilleby W, Stensvold A, Dahl AA. Fatigue and other adverse effects in men treated by pelvic radiation and long-term androgen deprivation for locally advanced prostate cancer. Acta Oncol. 2016;55(7):807–813. https://doi.org/10.3109/0284186X.2015.1127417 DOI: https://doi.org/10.3109/0284186X.2015.1127417
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