Desley van Zoggel

Improved outcomes for responders to induction chemotherapy 35 CHAPTER 3 Introduction Over the past decades, there have been significant improvements in the treatment of patients with rectal cancer. Due to the introduction of total mesorectal excision (TME) and the development of neoadjuvant (chemo)radiotherapy, the rate of locally recurrent rectal cancer (LRRC) has decreased from 20–30 to 6–10 percent.1–3 However, patients who develop LRRC remain to have a limited prognosis with 5-year overall survival rates of approximately 30 percent.4–7 The most important prognostic factor influencing survival after surgery is a clear resectionmargin (R0 resection).1,2,8–11 Achieving an R0 resection is challenging because of distorted anatomy due to previous TME surgery, the difficult distinction between fibrosis and malignant tissue after radiotherapy, and the ingrowth of the recurrent neoplasm into other structures, such as the adjacent organs, pelvic side wall, and the sacrum. To achieve downsizing of the local recurrence and consequently more R0 resections, neoadjuvant treatment with chemoradiotherapy is recommended.12 However, a proportion of patients with locally recurrent rectal cancer have already received (chemo)radiotherapy for their primary tumour. Previous studies have shown that in these patients reirradiation with a dose of 30 Gy combined with capecitabine is safe and effective.2,8 Alongside an R0 resection, a pathologic complete response (pCR) may be of prognostic value in predicting long-term outcomes for LRRC patients.13,14 Despite neoadjuvant treatment with chemo(re)irradiation, R0 resections are achieved in only 60 percent of cases and pCR rates are low (± 8 percent).7,15 The addition of induction chemotherapy to neoadjuvant chemo(re)irradiation may improve local downsizing and thereby improve the R0 resection and pCR rates. Furthermore, induction chemotherapy may eradicate occult micrometastases. Ultimately, this may improve long-termoncological outcomes. Our preliminary results showed a promising pCR rate with this treatment regimen.16 The current study evaluated the effect of induction chemotherapy administered prior to neoadjuvant chemo(re)irradiation on the pathologic response and the R0 resection rate in an extended cohort and the predictive value of the pathological response on oncological outcomes.