Rectal Sparing Approach After Preoperative Radio and/or Chemotherapy in Patients With Rectal Cancer

Introduction and rationale Neoadjuvant therapy, especially preoperative chemoradiotherapy (pCRT) and short-course radiotherapy followed by total mesorectal excision (TME), is the standard of treatment for mid-low rectal cancer. This approach significantly reduces the rate of local recurrence compared with surgery alone, with post-operative radiochemotherapy or with long-course radiotherapy alone.

Concerning the indication to neoadjuvant treatment and its regimen, there is still a wide discrepancy in the literature. Based on the dutch TME trial, showing a low rate of local recurrence in patients treated with short-course radiotherapy (RT) compared to TME alone, the neoadjuvant therapy indication for rectal cancer was RT short-course alone. Meanwhile, with German trial publication, the indication for rectal cancer treatment, up to 15 cm from anal verge, was combination between hyperfractionated RT and 5-fluorouracil based chemotherapy (CT). Two subsequent trials (Polish trial and Trans-Tasman Radiation Oncology Group trial) showed that RT short-course alone and CRT with hyperfractionated RT have similar oncological outcomes. Thus, in recent years there has been an increasing interest in the administration of neoadjuvant chemotherapy at therapeutic doses and not only radiosensitizers. Regimens are basically as follows: induction regimen and consolidation regimen. In the first case, CT precedes pCRT, while in consolidation regimen CT follows pCRT. The rationale for this strategy is that, currently, the mortality of rectal cancer comes from distant metastases and, given that only a full dose chemotherapy can prevent the occurrence of distant recurrence, the rationale for having chemotherapy as early as possible and in as many patients is feasible (patient compliance performing adjuvant chemotherapy is low, often for complications arising from surgery). More recently, studies have been published on the use of neoadjuvant chemotherapy alone and is currently underway in the US the PROSPECT trial evaluating the possibility of using the only neoadjuvant chemotherapy in selected cases instead of the classic CRT. For many reasons (enrolment of patients in clinical trials, refusal of patients to perform treatments considered standard and toxicity from radio and/or chemotherapy) is not uncommon in clinical practice to observe patients who performed unconventional treatments and not provided by any national or international guideline.

Positive and negative consequences of neoadjuvant treatment Neoadjuvant treatment followed by TME involve a high percentage of side effects associated with surgical complications both early and late, the toxicity associated with radiation or chemotherapy and alteration of bowel function, sexual, fecal continence and thus the quality of life (QoL). Among the advantages of neoadjuvant therapy, particularly the treatment associated CRT, it is notable that in 15-20% of cases have the disappearance of the primary tumor, or a pathologic complete response (pCR). Also lengthening the interval between pRT and/or CT and surgery is associated with an increased rate of pCR, therefore, unlike traditional 4-6 week intervals between the end of neoadjuvant therapy and surgery, currently there is tendency to perform surgery after 8-10 weeks, or even after 12 weeks. In patients with a pCR after neoadjuvant therapy, it have been showed a better outcome in long term than those who have a residual disease.

Rationale behind the rectum-sparing approach In order to avoid the morbidity and functional sequelae associated with neoadjuvant therapy followed by TME and based on excellent outcomes seen in patients with a pCR, it has been proposed that, in patients with a major clinical (mCR) or complete (cCR) response, you can opt for a conservative approach that includes preservation of the rectum. During recent years we are seeing a growing interest in these conservative approaches, as demonstrated by the increasing number of publications on this new therapeutic strategy that includes observation ("wait and see" policy) and local excision.

Local excision. LE is considered essentially an excisional biopsy and the decision to observe the patient (only follow-up) or run a TME after LE depends on the histologic features. Patients with no neoplasia (pCR) or with minimal residual disease (ypT1 with tumor regression grade <3 margins and free) are followed with close follow-up. In the remaining cases it opts for a subsequent intervention of TME. Studies concerning LE after neoadjuvant treatment are numerous with the principal lack is to be retrospective, with a low number and definition is not always clear and concordant for mCR and cCR. In addition, all these studies include patients who can not be subjected to radical surgery due to medical comorbidities or who reject the radical surgical treatment, especially when it is expected the final packaging of a stoma. More recently were published prospective studies both phase 2 and phase 3 that have consistently shown that LE is a feasible approach with oncological results comparable to the standard approach.