The multidisciplinary approach to the treatment of rectal cancer: 2015 update

Abstract

The multidisciplinary approach to the management of rectal cancer continues to evolve with developments in surgery, radiation therapy as well as systemic chemotherapy. Refinement of surgical techniques to improve organ preservation, selective use of neoadjuvant (or adjuvant) therapies, improvements in staging modalities and emerging criteria for the selection of tailored therapies are some of the advancements made over the last three decades. In addition, neoadjuvant treatment alternatives, multimodality sequencing and adaptive therapies based on treatment response continue to be a subject of clinical investigation. The current article reviews the salient topics related to the multidisciplinary treatment of resectable rectal cancer.

Keywords:

• adjuvant
• cancer
• chemotherapy
• imaging
• radiation
• rectal
• surgery
• targeted therapies

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Definitive surgery is the chief method for the treatment of locally advanced rectal adenocarcinoma. Total mesorectal excision is the standard surgical technique using either low anterior resection or abdominal perineal resection approaches when appropriate. At the present time, minimally invasive surgery for locally advanced rectal cancer is still investigational.

• Newly diagnosed rectal cancer patients should receive preoperative local staging with high-resolution MRI (or contrasted CT if high-resolution MRI unavailable), with consideration of transrectal EUS or endorectal MRI when available. Contrasted CT of the abdomen and pelvis is also used to evaluate for distant metastases.

• It has been demonstrated that both preoperative and postoperative radiation/chemoradiation improves local control in patients undergoing resection for rectal cancer, however, preoperative radiation is associated with improved local control and post-treatment bowel function when compared with postoperative therapy.

• Randomized trials have revealed that patient outcomes after postoperative chemoradiation therapy in resected, locally advanced, non-metastatic rectal cancer are superior to those observed when surgery alone was used.

• Improvements in preoperative staging coupled with advances in surgical techniques total mesorectal excision have spawned further investigation into stratification methods involving prognostic factors to better select those patients with T3N0 or T1-2N0 rectal cancer. As more data have been published, the standard of treatment has evolved to include neoadjuvant 5-FU-based chemoradiotherapy and adjuvant chemotherapy to prevent systemic recurrence. The use of combination chemotherapeutic regimens using oxaliplatin and irinotecan has been generally disappointing in improving response to neoadjuvant treatment.

• The current standard of care includes neoadjuvant continuous 5-FU-based chemoradiation and surgery for the majority of patients with node-positive or >T3 rectal cancer, followed by adjuvant chemotherapy (either with 5-FU, capecitabine or FOLFOX).

• Induction chemotherapy followed by chemoradiation is associated with improved compliance with systemic therapy and favorable pCR and DFS. While the improvement in these surrogate end points is encouraging, the effect on OS is a current subject of clinical investigation.

• Questions that remain to be answered include the benefits of short-course versus long-course chemoradiotherapy in locally advanced rectal cancer, the optimal timing of surgery and the most effective use of radiotherapy and surgery in patients with intermediate-stage disease.