Abstract Book

S236

ESTRO 37

individualized and multidisciplinary approach to cancer diagnosis. Patients who would benefit the most from PSA screening should be identified by evaluating their risk factors, comorbidity profiles, performance status, and life expectancy. Advanced novel tools, such as biomarkers and integrated imaging approaches, which can help in assessing the risk profile of each patient should be considered, thus abandoning the idea of performing blinded, systematic biopsies. SP-0457 Against the motion D.P. Dearnaley 1 1 Institute of Cancer Research, Academic Radiotherapy, London, United Kingdom Abstract text There is no doubt that there has been widespread overtreatment of early prostate cancer. Active surveillance (AS) 1 aims to avoid intervention in men who’s cancers are sufficiently indolent not to require treatment during their natural lifespan but to direct radical therapy to progressive cancers. Active surveillance programs using a variety of methodologies have been reported by a select group of academic centres in Europe and North America. There is no consensus on selection criteria for AS, the initial diagnostic work-up, or subsequent observation strategy. Although academic centres have produced very credible outcomes are these translatable to a broader community?, will the presently low rate of metastases development and prostate cancer be maintained?, will any role of AS change with the development of new image based diagnostic pathways? Whilst there may be little downside for AS in more elderly populations will this transfer to younger fit populations and different racial groups? The purpose of AS is to avoid the side effects of treatment. Increasingly sophisticated and convenient external beam radiotherapy and brachytherapy approaches, and focal therapy strategies are associated with low side effect profiles. The ProtecT trial 2 gives a clear indication of the potential risks of delaying treatment in a multicentre setting and that delayed intervention is not side effect free. To quote Anthony D’Amico “active surveillance shouldn’t be seen as a one-size fits all approach”. 1 C. Parker BJU International 2003 2 F.C. Hamdy et al NEJM 2016 SP-0458 Methods for 3D Voxel-based population analyses in NTCP modelling O. Acosta 1 1 LTSI-INSERM 1099, INSERM ADR Grand Ouest, NANTES CEDEX, France Abstract text To estimate the risk of radio-induced toxicities, current predictive models such as the Normal Tissue Complication Probability (NTCP) are mainly based on the dose-volume histograms (DVH)(Fiorino et al. 2009). The DVHs reduce however the 3D dose distribution to a unidimensional representation of the relationship between the fractional volume of an organ and a level of dose. There are therefore several limitations of using only the DVH within predictive models. The spatial information is lost by considering the organs as a whole volume thereby ignoring the local variability of the 3D dose distribution and the heterogeneous intra-organ radio sensitivity, which decreases the prediction capability. To address some of these issues, recent approaches aim at investigating the local relationships between dose and the side-effects by analyzing the dose at finer scales. For Symposium: Advanced dosimetry methods for dose- volume effects modelling

Abstract text The incidence of prostate cancer (PCa) has increased worldwide after PSA diffusion in the early nineties, although the mortality rate has remained stable or has slightly decreased. Up to 50% of the new PCa detected can be considered clinically insignificant or indolent. These kinds of disease have a very long natural history and the long-term benefits of therapies with radical intent are uncertain, with any intervention possibly representing an overtreatment. Active Surveillance (AS) is now embraced by the major international guidelines as an alternative to active treatment for selected early-stage tumors. AS strategy carefully considers four key components: (a) Identification of appropriate patients; (b) Patient education and reassurance; (c) Close monitoring over time, with serial PSA measurements, periodic biopsy, and (possibly) imaging studies; (d) Radical therapy for patients whose disease is reclassified as higher risk. AS protocols are designed to include patients with clinically insignificant cancer, i.e. patients with an index lesion volume of ≤0.5 cm 3 , Gleason Pattern Score (GPS) ≤3+3, and low PSA. These criteria are mostly based on the results of pathological studies performed in the 1990s and these clinical features are now being questioned. Some investigators are proposing to allow AS even for selected GPS=3+4 cancers when the amount of grade 4 disease is minimal. Some protocols are currently combining multi-parametric Magnetic Resonance Imaging findings and results from biopsies targeted on suspect lesions as a means to overcome the PCa volume limitation and to let patients with 3+3 PCa and any volume to be included in AS. AS entails close PCa monitoring over time, with radical therapy for those men with their disease reclassified to GP 4. Results of the phase II observational studies are demonstrating that AS is feasible and safe in the intermediate timeframe (7-10 yrs). If patients are selected properly and are followed carefully to allow early intervention upon evidence of reclassification, most men with indolent disease will not suffer from clinical disease progression or prostate cancer death, and those with more aggressive disease will still have an unmodified probability of being cured. Recently, the ProtecT (Prostate testing for cancer and Treatment) randomized trial showed that, after 10 years, in a population of patients with PSA-detected clinically localized prostate cancers, the prostate-cancer-specific mortality was very low (about 1%) and without significant differences among active monitoring (i.e. PSA kinetic monitoring without systematic biopsies), radical prostatectomy and external-beam radiotherapy. However, surgery and radiotherapy were associated with lower rates of disease progression and metastases, but the inclusion of patients belonging to different risk classes other than low risk and the monitoring without mandatory biopsies may represent biasing factors in the ProtecT setting. The appeal of AS also lies in its ability to use the observed natural history of the patient’s disease over time to identify patients who in fact have more aggressive disease. In my view, indolent PCa should be considered as a risk factor or a marker for more significant disease that may have been missed on the diagnostic biopsy or of a future progression to higher grade cancer. It should be managed, by secure monitoring, with possible delayed radical therapy for cancers which are reclassified as higher risk. Remaining in AS over time entails being confident of having an extremely low risk of progression. However the possible major future achievement would be disappearance of AS, with shift of the focus from avoiding overtreatment to avoiding overdiagnosis. To topple the process, there is a need to advance towards a more