Chapter 3 48 Discussion In this study, we observed a 17 percent pathologic complete response rate in patients with locally recurrent rectal cancer after treatment with induction chemotherapy and chemo(re)irradiation resulting in an excellent 3-year overall survival of 92 percent in these patients. In addition, this study shows pathologic response to be a powerful prognostic variable of improved oncological outcomes in LRRC patients, especially when an R0 resection has been achieved. Comparingthepathologiccompleteresponseratewiththe literature ischallenging, because dataare limitedonneoadjuvant treatment strategies for locallyrecurrent rectal cancer. The administrationof inductionchemotherapybefore chemoradiotherapyhas been studied to a greater extent in patientswith locally advanced rectal cancer (LARC), although evidence is mainly from retrospective nature or phase II trials. When focusing only on studies that administered either neoadjuvant CAPOX or FOLFOX followed by (chemo)radiotherapy, the results are inconsistent. Some studies showed a rather disappointing pCR rate when comparing their resultswith thepCRrateafter chemoradiotherapyaloneas reported inthe literature, whereas others demonstrated promising pCR rates ranging between 33 and 40 percent.20–27 ThepCRrateinourstudyisrather lowcomparedwiththelatterfindingsinLARC; however, it has to be noted that LRRC has proven to be relatively chemoradio-resistant. Hence, it is tobeexpectedthatpCRratesare lower inpatientswithrecurrentdiseaseeven if treatmentregimensarecomparable.ThepCRrateof 17percent iscomparablewithpCRrates after chemoradiotherapy forLARC.15 Whencomparingour resultswithpreviouslyreported pCR rates inpatientswithLRRC, our treatment regimenwith induction chemotherapy and chemoradiotherapy seems superior to treatment with neoadjuvant chemoradiotherapy aloneaspCRratesare17versus4–9percent respectively.14–16 Thecurrentfindingsare in line with the resultspublishedearlierbyour group inwhicha 17percent pCRratewasobserved after treatment with induction chemotherapy followed by reirradiation.16 Another study performed by our group demonstrated a 31 percent pCR rate, but it has to be noted that in this study only lateral recurrences were included, and these recurrences may represent a different etiology.28 The 92 percent 3-year OS for patients with a pCR in this study is superior to the survival rates reported for patients with LRRC after treatment with solely neoadjuvant (chemo) radiotherapy. For R0 resections, 3-yearOSvaries between40and55percent.1,10,11,29,30 Data on survival for LRRC patients with a pCR are limited. Wiig et al. showed a 80 percent 3-year survival for LRRC after pCR.14 Our preliminary results also showed a 3-year survival of 92 percent for patients with a pCR.16 Notably, more than half of complete responders had recurrent disease at 3 years.