Clinical Predictors of Acute Urinary Symptoms after Radiotherapy for Prostate Cancer

An interim study results presented at the 5th European Multidisciplinary Meeting on Urological Cancers

An interim study by Italian researchers showed that using a modelling programme together with IPSS questionnaire and dosage measure can predict the severity of acute urinary symptoms in patients with early prostate cancer who underwent radiotherapy. The findings were presented by Dr Cesare Cozzarini of the San Raffaele Scientific Institute, Milan, Italy at the 5th European Multidisciplinary Meeting on Urological Cancers (EMUC) held in Marseille, France (15-17 November 2013).

Created for practitioners in the fields of urology, medical oncology and radiotherapy, EMUC 2013 is organised in partnership between the European Association for Urology (EAU), the European Society for Medical Oncology (ESMO), the European Society for Radiotherapy and Oncology (ESTRO).

"Quantitative models predicting the risk of acute (and late) genito-urinary (GU) toxicity in patients treated with high dose radiotherapy for prostate cancer are lacking. This work represents one of the first attempts to provide radiation oncologists with quantitative tools to reliably predict the risk of moderate-severe acute GU effects based on both clinical and dosimetric individual parameters," according to Dr Cozzarini.

It is a prospective cohort study (DUE-01) which started in April 2010. The investigators aimed to develop predictive models of GU toxicity and erectile dysfunction after high dose radiotherapy for prostate cancer. Patients treated with conventional (1.8-2Gy/fr) or moderate hypo-fractionation (2.5-2.7Gy/fr) were included.

In their ad-interim analysis, the investigators also intended to find a link between pollakiuria, dysuria and nicturia as measured by IPSS at radiotherapy end and clinical/dosimetric risk factors. IPSS questionnaire at the start and at the end of radiotherapy were prospectively collected by the researchers and planning data were recovered and analyzed with a dedicated program (Vodca, MSS GmbH, Zurich), including absolute (cc/cm2) and % bladder dose-volume/surface (DVH/DSH) parameters referred to both the whole treatment and to the weekly delivered dose (DVHw/DSHw).

In the study, relevant clinical factors were also prospectively collected including T stage, concomitant morbidities and drugs, use of hormonal therapy, previous surgery, smoking, age, body-mass index and prostate volume. In IPSS, each item ranges from 0 to 5 with increasing score which indicates increasing toxicity severity: for each question, a score ≥4 at the end of the therapy was considered as the end point.

At the time of the analysis (January 2013), 339 patients have been enrolled by nine institutes. Clinical data of 212/339 patients were available (93 patients treated with conventional radiotherapy and 119 patients treated with hypo-fractionation). Of 172/212 patients both baseline and end-radiotherapy IPSS were collected. For 179/212 patients also DVH/DSH were available. Questions on pollakiuria, dysuria and nicturia (respectively 2, 3 and 7) showed the larger increase of the fraction of patients with scores ≥4 between basal and end questionnaire; consequently, the analysis focused on these symptoms.

The number of patients with scores ≥4 increased from 8 to 30 for pollakiuria, from 5 to 20 for dysuria and from 12 to 34 for nicturia. At MVA (overall p < 0.0001), the main independent predictors of acute pollakiuria, were: smoking (OR: 2.74, p = 0.04) and S8.5w (OR:1.01, p = 0.10); AUC=0.66. The model was confirmed also after the exclusion of patients with baseline IPSS-pollakiuria ≥4 (AUC=0.69).

In this study, the researchers prospectively collect patient-reported information concerning GU toxicity and erectile dysfunction before, during and at the end of radiotherapy and for a period of five years after its completion. The study therefore has a high probability of helping to develop highly reliable models for the prediction of acute and late GU toxicity and erectile dysfunction and their impact on quality of life, according to Dr Cozzarini.

The study authors expect that the final results will have a significant impact on the evolution of radiotherapy of prostate cancer in the next five to 10 years leading to a significant reduction of GU toxicity and sexual dysfunction, leading to a more refined tailoring of the radiation therapy.