Phase II trial Late gastrointestinal and urogenital side-effects after radiotherapy – Incidence and prevalence. Subgroup-analysis within the prospective Austrian–German phase II multicenter trial for localized prostate cancer Maximilian P. Schmid a , Richard Pötter a , Valentin Bombosch a , Samir Sljivic a , Christian Kirisits a , Wolfgang Dörr a,b , Gregor Goldner a,⇑ a University of Vienna Medical School, Austria; b University of Technology Dresden, Germany article info Article history: Received 23 August 2011 Received in revised form 16 May 2012 Accepted 22 May 2012 Available online 23 June 2012 Keywords: Prostate cancer Radiotherapy Dose-escalation Late side-effects Reporting abstract Purpose: In general late side-effects after prostate cancer radiotherapy are presented by the use of actu- arial incidence rates. The aim of this analysis was to describe additional relevant aspects of late side effects after prostate cancer radiotherapy. Materials and methods: All 178 primary prostate-cancer patients were treated within the Austrian–Ger- man multicenter trial by three-dimensional radiotherapy up to a local dose of 70 Gy (low/intermediate- risk) or 74 Gy (high-risk), respectively. Late gastrointestinal/urogenital (GI/GU) side-effects were pro- spectively assessed by the use of EORTC/RTOG score. Maximum side-effects, actuarial incidence rate and prevalence rates, initial appearance and duration of Pgrade 2 toxicity were evaluated. Results: Median follow-up was 74 months. Late GI/GU side-effects Pgrade 2 were detected in 15% (27/ 178) and 22% (40/178). The corresponding 5-year actuarial incidence rates for GI/GU side-effects were 19% and 23%, whereas the prevalence was 1–2% and 2–7% after 5 years, respectively. Late side effects Pgrade 2 appeared within 5 years after radiotherapy in all patients with GI side-effects (27/27) and in 85% (34/40) of the patients with GU side-effects, respectively and lasted for less than 3 years in 90% (GI) and 98% (GU). Conclusions: This study demonstrates that the majority of late GI and GU side effects after primary exter- nal beam radiotherapy for prostate cancer are transient. Using only actuarial incidence rates for reporting side effects may lead to misinterpretation or overestimation. The combination of incidence and preva- lence rates provides a more comprehensive view on the complex issue of late side effects. Ó 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 104 (2012) 114–118 Assessment of treatment-related side-effects is one of the most important issues in medicine in general, and in the field of radio- therapy in particular due to the occurrence of late side effects. Pre- cise knowledge of side effects (together with the therapeutic effect) allows an estimation of the therapeutic ratio and thus giving the opportunity to determine the specific benefit of a dedicated therapy for each individual patient – especially if different treat- ment modalities are accessible for the same disease. In the treatment of localized prostate cancer, radiotherapy, sur- gery or a combination of both is the (curative) therapy of choice [1]. High biochemical control rates, local control rates and survival rates are reported by both treatment modalities [2–9]. The decision concerning which treatment is applied is mainly driven by the per- sonal preference, the individual health status and treatment re- lated side-effects. The most frequently reported side-effects are urinary and stool urgency/incontinence and rectal bleeding in pa- tients treated by radiotherapy and urinary incontinence and erec- tile dysfunction in patients treated by surgery [2–12]. In the treatment of prostate cancer by 3D conformal external beam radiotherapy (EBRT) or intensity modulated radiotherapy (IMRT) using high dose regimes with 74–81 Gy, late side effect rates (Pgrade 2) after 5–10 years ranging from 5–39% for the gas- trointestinal (GI) tract and 13–39% for the genitourinary (GU) tract were reported in the literature [2–8]. The common practice to report these side-effects is by applying the Kaplan–Meier method for assessing actuarial incidence rates. Actuarial incidence rates for late side effects estimate the risk to develop a defined maximum grade of side-effects at least once within a certain time period. No information with regard of dura- tion and further development is being reflected by actuarial inci- dence rates. However, late side effects after prostate cancer radiotherapy seem to improve over time [13–16]. Therefore prev- alence rates, which indicate the percentage of patients at risk suf- fering from late side effects at a defined time point, may provide a clinically more meaningful estimate of the risk of late side effects [13,14,16,17]. The additional information gathered from preva- 0167-8140/$ - see front matter Ó 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.radonc.2012.05.007 ⇑ Corresponding author. Address: Department of Radiotherapy and Radiobiology, University Hospital of Vienna, Währinger Gürtel 18-20, A – 1090 Vienna, Austria. E-mail address: Gregor.Goldner@akhwien.at (G. Goldner). Radiotherapy and Oncology 104 (2012) 114–118 Contents lists available at SciVerse ScienceDirect Radiotherapy and Oncology journal homepage: www.thegreenjournal.com