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Neoadjuvant CRT followed by TME surgery remains standard of care for rectal cancer in SG

Stephen Padilla
11 Jul 2018

Neoadjuvant chemoradiotherapy (CRT) is still the standard of care for locally advanced rectal cancer in a local population, according to a Singapore study, adding that outcomes are similar to international published data.

“Neoadjuvant CRT followed by total mesorectal excision (TME) surgery for locally advanced rectal cancer has been shown to improve local control and reduce toxicity, as compared to adjuvant CRT,” researchers said.

A total of 117 patients with T3/4, N0/+, M0 rectal cancer received neoadjuvant CRT followed by TME surgery from April 2002 to December 2014. Treatment regimen consisted of a total RT dose of 50.4 Gy in 28 daily fractions delivered concurrently with 5-fluorouracil or capecitabine chemotherapy over 5.5 weeks. All patients were scheduled for TME surgery.

The following outcomes were then analysed: local control, disease-free survival, overall survival and treatment toxicities.

Over a median follow-up of 34 months (range, 2–112), 11.5 percent (13/113) of patients achieved a pathological complete response (pCR), and 72.6 percent (85/117) had either tumour or nodal downstaging following neoadjuvant CRT. [Singapore Med J 2018;59:305-310]

Grade 3 acute (dermatitis and diarrhoea) and late (fistula and stricture) toxicities were reported in 5.2 percent (5/96) and 3.1 percent (3/96) of patients, respectively. No grade 4 toxicity was reported. The 5-year local recurrence rate was 4.5 percent, while the disease-free and overall survival rates were 65.7 percent and 80.6 percent, respectively.

“These results are comparable to published data,” researchers said. [N Engl J Med 2004;351:1731-1740]

In multivariate analysis, nodal positivity predicted poor disease-free survival and poor overall survival. Furthermore, tumour downstaging and pCR did not improve outcomes.

In a pooled analysis of individual patient data, patients with locally advanced rectal cancer who achieved pCR following preoperative CRT had an improved 5-year disease survival rate of 83.3 percent vs 65.6 percent for those who did not achieve pCR. [Lancet Oncol 2010;11:835-844]

Several studies have examined strategies to improve pCR rates. These strategies are as follows: escalation of RT dose in the preoperative setting, preoperative CRT with combination chemotherapy, and delivery of chemotherapy in the interval period between completion of CRT and surgery. [Radiat Oncol 2014;9:70; J Chin Med Assoc 2014;77:128-132; Dis Colon Rectum 2009;52:1927-1934]

“However, our results showed that pCR after preoperative CRT did not improve disease-free survival or overall survival in our patients. In addition, tumour downstaging was not associated with improved outcomes. This was likely due to the small number of patients in our study,” researchers said.

Research in personalized patient treatment using predictive biomarkers to predict response to neoadjuvant therapy is ongoing, according to researchers, adding that studies such as this could change the way clinicians manage patients.

“Meanwhile, the favourable outcomes of neoadjuvant CRT followed by TME surgery for locally advanced rectal cancer, in our institutional experience, support the continuation of this multimodality treatment for our local population,” they said.

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