Predictors of Patient-Reported Incontinence at Adjuvant/Salvage Radiotherapy after Prostatectomy: Impact of Time between Surgery and Radiotherapy

Fernando Munoz, Giuseppe Sanguineti, Andrea Bresolin, Domenico Cante, Vittorio Vavassori, Justina Magdalena Waskiewicz, Giuseppe Girelli, Barbara Avuzzi, Elisabetta Garibaldi, Adriana Faiella, Elisa Villa, Alessandro Magli, Barbara Noris Chiorda, Marco Gatti, Tiziana Rancati, Riccardo Valdagni, Nadia G Di Muzio, Claudio Fiorino, Cesare Cozzarini, Fernando Munoz, Giuseppe Sanguineti, Andrea Bresolin, Domenico Cante, Vittorio Vavassori, Justina Magdalena Waskiewicz, Giuseppe Girelli, Barbara Avuzzi, Elisabetta Garibaldi, Adriana Faiella, Elisa Villa, Alessandro Magli, Barbara Noris Chiorda, Marco Gatti, Tiziana Rancati, Riccardo Valdagni, Nadia G Di Muzio, Claudio Fiorino, Cesare Cozzarini

Abstract

Background: Baseline urinary incontinence (UI) strongly modulates UI recovery after adjuvant/salvage radiotherapy (ART/SRT), inducing clinicians to postpone it "as much as possible", maximizing UI recovery but possibly reducing efficacy. This series aims to analyze the trend of UI recovery and its predictors at radiotherapy start.

Methods: A population of 408 patients treated with ART/SRT enrolled in a cohort study (ClinicalTrials.gov #NCT02803086) aimed at developing predictive models of radiation-induced toxicities. Self-reported UI and personality traits, evaluated by means of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) and Eysenck Personality Questionnaire - Revised (EPQ-R) questionnaires, were assessed at ART/SRT start. Several endpoints based on baseline ICIQ-SF were investigated: frequency and amount of urine loss (ICIQ3 and ICIQ4, respectively), "objective" UI (ICIQ3 + 4), "subjective" UI (ICIQ5), and "TOTAL" UI (ICIQ3 +4 + 5). The relationship between each endpoint and time from prostatectomy to radiotherapy (TTRT) was investigated. The association between clinical and personality variables and each endpoint was tested by uni- and multivariable logistic regression.

Results: TTRT was the strongest predictor for all endpoints (p-values ≤ 0.001); all scores improved between 4 and 8 months after prostatectomy, without any additional long-term recovery. Neuroticism independently predicted subjective UI, TOTAL UI, and daily frequency.

Conclusions: Early UI recovery mostly depends on TTRT with no further improvement after 8 months from prostatectomy. Higher levels of neuroticism may overestimate UI.

Keywords: EPQ-R; ICIQ-SF; adjuvant radiotherapy; prostatectomy; salvage radiotherapy; urinary incontinence.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
A plot of the relationship between incontinence symptoms and time elapsed between prostatectomy and post-prostatectomy radiotherapy. Incontinence was evaluated through the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF). Points represent the mean values of the ICIQ score in each decile interval; bars show the standard deviations and continuous lines and the fit between the data and a sigmoid curve. Each plot is associated with the frequency (a) and amount (b) of urine leakage, the subjective perceived quality of life (c), the objective (d), and total (e) estimation of urinary incontinence, respectively. The time axis for endpoint (a) covered the last decile to show the entire plateau (the same behavior was found for all the remaining endpoints). For the remaining endpoints, the scale was restricted to the first 3-years to render the results more easily comprehensible.
Figure 2
Figure 2
A plot of the fraction of “completely dry” patients (showing ICIQ3 + ICIQ4 = 0) against the time between prostatectomy and radiotherapy. The rate increased sharply between 4 and 10 months after surgery, reaching a plateau value of around 40% even at much longer periods.

References

    1. Vale C.L., Fisher D., Kneebone A., Parker C., Pearse M., Richaud P., Sargos P., Sydes M.R., Brawley C., Brihoum M., et al. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: A prospectively planned systematic review and meta-analysis of aggregate data. Lancet. 2020;396:1422–1431. doi: 10.1016/S0140-6736(20)31952-8.
    1. Parker C.C., Clarke N.W., Cook A.D., Kynaston H.G., Petersen P.M., Catton C., Cross W., Logue J., Parulekar W., Payne H., et al. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): A randomized controlled phase 3 trial. Lancet. 2020;396:1413–1421. doi: 10.1016/S0140-6736(20)31553-1.
    1. Sargos P., Chabaud S., Latorzeff I., Magné N., Benyoucef A., Supiot S., Pasquier D., Abdiche M.S., Gilliot O., Graff-Cailleaud P., et al. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): A randomised, phase 3 trial. Lancet Oncol. 2020;21:1341–1352. doi: 10.1016/S1470-2045(20)30454-X.
    1. Kneebone A., Fraser-Browne C., Duchesne G.M., Fisher R., Frydenberg M., Herschtal A., Williams S.G., Brown C., Delprado W., Haworth A., et al. Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): A randomised, controlled, phase 3, non-inferiority trial. Lancet Oncol. 2020;21:1331–1340. doi: 10.1016/S1470-2045(20)30456-3.
    1. Nyarangi-Dix J.N., Steimer J., Bruckner T., Jakobi H., Koerber S.A., Hadaschik B., Debus J., Hohenfellner M. Post-prostatectomy radiotherapy adversely affects urinary continence irrespective of radiotherapy regime. World J. Urol. 2017;35:1841–1847. doi: 10.1007/s00345-017-2081-x.
    1. Ávila M., Becerra V., Guedea F., Suárez J.F., Fernandez P., Macías V., Mariño A., Hervás A., Herruzo I., Ortiz M.J., et al. Estimating preferences for treatments in patients with localized prostate cancer. Int. J. Radiat. Oncol. 2015;91:277–287. doi: 10.1016/j.ijrobp.2014.09.044.
    1. Hoffman R.M., Lo M., Clark J.A., Albertsen P.C., Barry M.J., Goodman M., Penson D.F., Stanford J.L., Stroup A.M., Hamilton A.S. Treatment decision regret among long-term survivors of localized prostate cancer: Results from the prostate cancer outcomes study. J. Clin. Oncol. 2017;35:2306–2314. doi: 10.1200/JCO.2016.70.6317.
    1. Tendulkar R.D., Agrawal S., Gao T., Efstathiou J.A., Pisansky T.M., Michalski J.M., Koontz B.F., Hamstra D.A., Feng F.Y., Liauw S.L., et al. Contemporary update of a multi-institutional predictive nomogram for salvage radiotherapy after radical prostatectomy. J. Clin. Oncol. 2016;34:3648–3654. doi: 10.1200/JCO.2016.67.9647.
    1. Fiorino C., Broggi S., Fossati N., Cozzarini C., Goldner G., Wiegel T., Hinkelbein W., Karnes R.J., Boorjian S.A., Haustermans K., et al. Predicting the 5-year risk of biochemical relapse after postprostatectomy radiation therapy in ≥ PT2, pN0 patients with a comprehensive tumor control probability model. Int. J. Radiat. Oncol. 2016;96:333–340. doi: 10.1016/j.ijrobp.2016.06.014.
    1. Thompson I.M., Valicenti R.K., Albertsen P.C., Davis B., Goldenberg S.L., Hahn C., Klein E.A., Michalski J.M., Roach M., Sartor O., et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO guideline. J. Urol. 2013;190:441–449. doi: 10.1016/j.juro.2013.05.032.
    1. Suardi N., Gallina A., Lista G., Gandaglia G., Abdollah F., Capitanio U., Dell’Oglio P., Nini A., Salonia A., Montorsi F., et al. Impact of adjuvant radiation therapy on urinary continence recovery after radical prostatectomy. Eur. Urol. 2014;65:546–551. doi: 10.1016/j.eururo.2013.01.027.
    1. Zaffuto E., Gandaglia G., Fossati N., Dell’Oglio P., Moschini M., Cucchiara V., Suardi N., Mirone V., Bandini M., Shariat S.F., et al. Early postoperative radiotherapy is associated with worse functional outcomes in patients with prostate cancer. J. Urol. 2017;197:669–675. doi: 10.1016/j.juro.2016.09.079.
    1. van Stam M.A., Aaronson N.K., Pos F.J., Bosch J.R., Kieffer J.M., Tillier C.N., van der Poel H.G. The effect of salvage radiotherapy and its timing on the health-related quality of life of prostate cancer patients. Eur. Urol. 2016;70:751–757. doi: 10.1016/j.eururo.2016.03.010.
    1. Adam M., Tennstedt P., Lanwehr D., Tilki D., Steuber T., Beyer B., Thederan I., Heinzer H., Haese A., Salomon G., et al. Functional outcomes and quality of life after radical prostatectomy only versus a combination of prostatectomy with radiation and hormonal therapy. Eur. Urol. 2017;71:330–336. doi: 10.1016/j.eururo.2016.11.015.
    1. Pinkawa M., Fischedick K., Asadpour B., Gagel B.D., Piroth M.D., Holy R., Krenkel B., Eble M.J. Health-related quality of life after adjuvant and salvage postoperative radiotherapy for prostate cancer—A prospective analysis. Radiother. Oncol. 2008;88:135–139. doi: 10.1016/j.radonc.2007.10.022.
    1. Sowerby R.J., Gani Y., Yim H., Radomsky S.B., Catton C. Long-term complications in men who have early or late radiotherapy after radical prostatectomy. Can. Urol. Assoc. J. 2014;8:253–258. doi: 10.5489/cuaj.1764.
    1. Vogel M.M.E., Kessel K.A., Gschwend J.E., Weichert W., Wilkens J.J., Combs S.E. Early and late toxicity profiles of patients receiving immediate postoperative radiotherapy versus salvage radiotherapy for prostate cancer after prostatectomy. Strahlenther. Onkol. 2018;195:131–144. doi: 10.1007/s00066-018-1359-2.
    1. Donovan J.L., Hamdy F.C., Lane J.A., Mason M., Metcalfe C., Walsh E., Blazeby J.M., Peters T.J., Holding P., Bonnington S., et al. Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N. Engl. J. Med. 2016;375:1425–1437. doi: 10.1056/NEJMoa1606221.
    1. Budäus L., Bolla M., Bossi A., Cozzarini C., Crook J., Widmark A., Wiegel T. Functional outcomes and complications following radiation therapy for prostate cancer: A critical analysis of the literature. Eur. Urol. 2012;61:112–127. doi: 10.1016/j.eururo.2011.09.027.
    1. Sini C., Chiorda B.N., Gabriele P., Sanguineti G., Morlino S., Badenchini F., Cante D., Carillo V., Gaetano M., Giandini T., et al. Patient-reported intestinal toxicity from whole pelvis intensity-modulated radiotherapy: First quantification of bowel dose-volume effects. Radiother. Oncol. 2017;124:296–301. doi: 10.1016/j.radonc.2017.07.005.
    1. Sini C., Fiorino C., Perna L., Chiorda B.N., Deantoni C.L., Bianchi M., Sacco V., Briganti A., Montorsi F., Calandrino R., et al. Dose-volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation. Radiother. Oncol. 2016;118:79–84. doi: 10.1016/j.radonc.2015.11.020.
    1. Cozzarini C., Chiorda B.N., Sini C., Fiorino C., Briganti A., Montorsi F., Di Muzio N. Hematologic toxicity in patients treated with postprostatectomy whole-pelvis irradiation with different intensity modulated radiation therapy techniques is not negligible and is prolonged: Preliminary results of a longitudinal, observational study. Int. J. Radiat. Oncol. 2016;95:690–695. doi: 10.1016/j.ijrobp.2016.01.022.
    1. Avery K., Donovan J., Peters T.J., Shaw C., Gotoh M., Abrams P. ICIQ: A brief and robust measure for evaluating the symptoms and impact of urinary incontinence. Neurourol. Urodyn. 2004;23:322–330. doi: 10.1002/nau.20041.
    1. Francis L.J., Brown L.B., Philipchalk R. The development of an abbreviated form of the revised Eysenck personality questionnaire (EPQR-A): Its use among students in England, Canada, the U.S.A. and Australia. Pers. Individ. Differ. 1992;13:443–449. doi: 10.1016/0191-8869(92)90073-X.
    1. Landoni V., Fiorino C., Cozzarini C., Sanguineti G., Valdagni R., Rancati T. Predicting toxicity in radiotherapy for prostate cancer. Phys. Med. 2016;32:521–532. doi: 10.1016/j.ejmp.2016.03.003.
    1. Cozzarini C., Rancati T., Palorini F., Avuzzi B., Garibaldi E., Balestrini D., Cante D., Munoz F., Franco P., Girelli G., et al. Patient-reported urinary incontinence after radiotherapy for prostate cancer: Quantifying the dose-effect. Radiother. Oncol. 2017;125:101–106. doi: 10.1016/j.radonc.2017.07.029.
    1. Barry M.J., Gallagher P.M., Skinner J.S., Fowler F.J. Adverse effects of robotic-assisted laparoscopic versus open retropubic radical prostatectomy among a nationwide random sample of medicare-age men. J. Clin. Oncol. 2012;30:513–518. doi: 10.1200/JCO.2011.36.8621.
    1. Nyberga M., Hugossonc J., Wiklund P., Sjoberg D., Wilderäng U., Carlsson S.V., Carlsson S., Stranne J., Steineck G., Haglind E., et al. Functional and oncologic outcomes between open and robotic radical prostatectomy at 24-month follow-up in the Swedish LAPPRO trial. Eur. Urol. Oncol. 2018;1:353–360. doi: 10.1016/j.euo.2018.04.012.
    1. Ávila M., Patel L., López S., Cortes-Sanabría L., Garín O., Pont À., Ferrer F., Boladeras A., Zamora V., Fosså S., et al. Patient-reported outcomes after treatment for clinically localized prostate cancer: A systematic review and meta-analysis. Cancer Treat. Rev. 2018;66:23–44. doi: 10.1016/j.ctrv.2018.03.005.
    1. Leufgens F., Berneking V., Vögeli T.-A., Kirschner-Hermanns R., Eble M.J., Pinkawa M. Quality of life changes >10 years after postoperative radiation therapy after radical prostatectomy for prostate cancer. Int. J. Radiat. Oncol. 2019;105:382–388. doi: 10.1016/j.ijrobp.2019.06.004.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere