Impact of a history of metastases or synchronous metastases on survival in patients with locally recurrent rectal cancer.

AIM: Patients with locally recurrent rectal cancer (LRRC) frequently present with either synchronous metastases or a history of metastases. This study was conducted to evaluate whether LRRC patients without metastases have a different oncological outcome compared to patients with a history of metastases treated with curative intent or patients with potentially curable synchronous metastases. METHOD: All consecutive LRRC patients who underwent intentionally curative surgery between 2005 and 2017 in a large tertiary hospital were retrospectively reviewed and categorized as having no metastases, a history of (curatively treated) metastases or synchronous metastases. Patients with unresectable distant metastases were excluded from the analysis. RESULTS: Of the 349 patients who were analysed, 261 (75%) had no metastases, 42 (12%) had a history of metastases and 46 (13%) had synchronous metastases. The 3-year metastasis-free survival was 52%, 33% and 13% in patients without metastases, with a history of metastases, and with synchronous metastases, respectively (P < 0.001) A history of metastases did not influence overall survival (OS), but there was a trend towards a worse OS in patients with synchronous metastases compared with patients without synchronous metastases (hazard ratio 1.43; 95% CI 0.98-2.11). CONCLUSION: LRRC patients with a history of curatively treated metastases have an OS comparable to that in patients without metastases and should therefore be treated with curative intent. However, LRRC patients with synchronous metastases have a poor metastasis-free survival and worse OS; in these patients, an individualized treatment approach to observe the behaviour of the disease is recommended.

Improved Outcomes for Responders After Treatment with Induction Chemotherapy and Chemo(re)irradiation for Locally Recurrent Rectal Cancer.

BACKGROUND: Despite improvements in the multimodality treatment for patients with locally recurrent rectal cancer (LRRC), oncological outcomes remain poor. This study evaluated the effect of induction chemotherapy and subsequent chemo(re)irradiation on the pathologic response and the rate of resections with clear margins (R0 resection) in relation to long-term oncological outcomes. METHODS: All consecutive patients with LRRC treated in the Catharina Hospital Eindhoven who underwent a resection after treatment with induction chemotherapy and subsequent chemo(re)irradiation between January 2010 and December 2018 were retrospectively reviewed. Induction chemotherapy consisted of CAPOX/FOLFOX. Endpoints were pathologic response, resection margin and overall survival (OS), disease free survival (DFS), local recurrence free survival (LRFS), and metastasis free survival (MFS). RESULTS: A pathologic complete response was observed in 22 patients (17%), a "good" response (Mandard 2-3) in 74 patients (56%), and a "poor" response (Mandard 4-5) in 36 patients (27%). An R0 resection was obtained in 83 patients (63%). The degree of pathologic response was linearly correlated with the R0 resection rate (p = 0.026). In patients without synchronous metastases, pathologic response was an independent predictor for LRFS, MFS, and DFS (p = 0.004, p = 0.003, and p = 0.024, respectively), whereas R0 resection was an independent predictor for LRFS and OS (p = 0.020 and p = 0.028, respectively). CONCLUSIONS: Induction chemotherapy in addition to neoadjuvant chemo(re)irradiation is a promising treatment strategy for patients with LRRC with high pathologic response rates that translate into improved oncological outcomes, especially when an R0 resection has been achieved.

Preliminary results of a cohort study of induction chemotherapy-based treatment for locally recurrent rectal cancer.

BACKGROUND: A significant number of patients treated for locally recurrent rectal cancer have local or systemic failure, especially after incomplete surgical resection. Neoadjuvant treatment regimens in patients who have already undergone preoperative (chemo)radiotherapy for the primary tumour are limited. The objective of the present study was to evaluate the influence of a neoadjuvant regimen incorporating induction chemotherapy (ICT) in patients with locally recurrent rectal cancer who had preoperative (chemo)radiotherapy for the primary cancer or an earlier local recurrence. METHODS: Patients were treated with a sequential neoadjuvant regimen including three or four cycles of 5-fluorouracil and oxaliplatin-containing chemotherapy. When no progressive disease was found at evaluation, neoadjuvant treatment was continued with chemoradiation therapy (CRRT) using 30 Gy with concomitant capecitabine. If there was a response to ICT, the patient was advised to continue with systemic chemotherapy after CRRT as consolidation chemotherapy while waiting for resection. These patients were compared with patients who received CRRT alone in the same time interval. RESULTS: Of 58 patients who had ICT, 32 (55 per cent) had surgery with clear resection margins, of whom ten (17 per cent) exhibited a pathological complete response (pCR). The remaining 26 patients had 23 R1 and three R2 resections. In 71 patients who received CRRT, a similar rate of R0 (35 patients) and R1 (36) resection was found (P = 0·506), but only three patients (4 per cent) had a pCR (P = 0·015). CONCLUSION: The incorporation of ICT in neoadjuvant regimens for locally recurrent rectal cancer is a promising strategy.