Desley van Zoggel

Summary, discussion and future perspectives 149 CHAPTER 8 Future perspectives Response toneoadjuvant treatment andoncologicoutcome seemtocorrelate. Thisfinding mayguidedecisionmakingat anMDT.However, it isstill not clear if response isapredictive factor or just a selection tool for intrinsic good prognostic patients. If it is only a selection tool, intensificationof neoadjuvant treatment byadding ICTwill not alter outcomeandwill result inaddedmorbidity. Basedonourpreliminaryresultsof ICTaprospectiverandomized trial comparingLRRCpatients receivingonly (re)irradiationandagroupalsoreceiving ICT. Theprimaryobjectiveof thisstudy is todemonstrate that intensificationof theneoadjuvant treatment leads to a higher clear resection margin rate. The second objective is to show a better oncological outcome by reducing the development of distant metastatic disease, which is themaincauseof treatment failure. Incaseof apositiveresult inthe treatment arm, thiswill have an impact for the guidelines for the treatment of LRRC. Guidelines, which are still lacking due to the uncertainties regarding preoperative treatment. The PELVEX 2 has beenstarted inearly2021 and is recruitingpatients. Intotal 364patientsneedtobe included in this international multicentre study. Another interesting study is themulticentreFrenchGRECCAR 15 study, which randomizes between preoperative ICT and preoperative ICT followed by reirradiation in patients who received radiotherapy for their primary rectal cancer. So in this study not ICT is the experimental basis, but reirradiation. This studywill still shed light on theuseof ICTand its radiosensitizingeffect of reirradiation.However, in this studynoexternal or intraoperative boostwill bedeliveredand it is really thequestion if the radiosensitizingeffect is enough to trigger an effect in the relatively low reirradiation dose. The focus of LRRC management has always been on gaining optimal local control and the surgical challenges involved to achieve this. Not achieving a clear resectionmargin was considered the main cause for treatment failure and progression of disease. If achieving a response would lead to a better oncologic outcome, this will mean that not only local control is important, but also treatment of micrometastatic disease will be equally important. It would not be exaggerated to say that thiswould be a paradigmshift for the treatment of LRRC. Instead of advising upfront surgery, a more conservative approachwith neoadjuvant treatment and repeatedmonitoring of response in order to understand the biological behaviour in a specific patient would become the standard. The role of imaging will be even more pivotal at MDTs as it was before. It can also be expected that patients will enter longer observation periods, possibly even leading to a more conservative approach in complete responders and a non-surgical palliative approach in those who progress. The management will be more complex and should be restricted to highly specialized centres.