Late side effects after image-guided intensity modulated radiotherapy compared to 3D-conformal radiotherapy for prostate cancer: results from two prospective cohorts
Menée sur 431 patients atteints d'un cancer de la prostate de stade localisé, cette étude compare les effets secondaires à long terme d'une radiothérapie conformationnelle 3D et d'une radiothérapie avec modulation d'intensité et guidage par imagerie
Purpose : Technical developments in the field of external beam radiotherapy enabled the clinical introduction of Image-Guided Intensity Modulated Radiotherapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation techniques (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating two prospective cohorts of men treated for localized prostate cancer, in order to investigate the hypothesized reductions in toxicity. Methods and Methods : Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78 Gy in 39 fractions were recruited from two Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90 days after treatment) was derived from self-assessment questionnaires and case report forms, according to RTOG-EORTC scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors. Results : The five-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted HR=0.59, p=0.005), with significant reductions in proctitis (HR=0.37, p=0.047) and increased stool frequency (HR=0.23, p<0.001). GU grade ≥2 toxicity levels at 5 years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR=1.19, p=0.33). Other strong predictors (p<0.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age. Conclusions : Treatment with IG-IMRT reduced the risk of late grade ≥2 complications, whereas GU toxicities remained comparable. This clinically relevant observation demonstrates that IMRT and image-guidance should therefore be the preferred treatment option, provided that margin reduction is implemented with caution.