Colorectal cancer (CRC) is the fourth most frequently diagnosed malignancy in both sexes and the second most common cause of cancer death in the world [1]. The advent of neoadjuvant radiotherapy in association with TME (Total Mesorectal Excision) surgery described by RJ Heald in 1982 [2]. has transformed the management of locally advanced forms (T3 T4 and/or N +) of middle and low rectal cancer, with a significant gain on local recurrence and an improvement in overall survival [3]. The association of chemotherapy with radiotherapy has further improved the carcinological and functional prognosis of this disease, favoring tumor regression (downstaging) or even tumor sterilization in some cases (4). An interval of six to eight weeks between the end of radiochemotherapy (RCT) and surgery is recommended to optimize this tumor response and minimize toxicity [5]. In the literature, the tumor response correlates with recurrence-free survival and overall survival [6]. However, not all patients have the same sensitivity to this RCT: some tumors may not respond well to this treatment when others respond well.

The aim of this retrospective study was to identify the potential clinical, pathological, and therapeutic that could predict tumor response (complete pathologic response or downstaging to neoadjuvant RCT.

Between January 2009 and December 2014, 90 patients underwent preoperative RCT at the radiotherapy department at University Hospital Mohamed VI, Oujda, Morocco.

Pathologic examination of resected specimens revealed a complete histopathological response (PCR) in 06 patients (15%). Downstaging to ypT2 or less was observed in 19 patients (47,5%). Twenty-one patients (52,5%) showed no downstaging of either T or N stage and were classified as non-responders (Tabl 3). The tumor was classified as ypT0 in 6 patients (15%), ypT1 in 4 (10%), ypT2 in 9 (22.5%), ypT3 in 19 (47.5%) and ypT4 in two (5%).

The univariate analysis indicated that the circumferential extent of the tumor was significantly associated with tumor downstaging (p = 0.007) and with a complete tumor response (p = 0.001). However, a delay between RCT and surgery ≥ 8 weeks was a significant predictive factor for downstaging (p = 0.02). Other variables (sex, age, Tumor localization, tumor fixation, anemia, Distance from the anal verge, Tumor differentiation, clinical T classification, clinical lymph node (N) classification, radiation dose) were not significantly correlated with downstaging (Tabl 4 and Tabl 5).

The factors that predict the response to neoadjuvant radiation chemotherapy in rectal cancer has not yet been well determined. Some recent studies also have investigated potential predictors of PCR and downstaging.

Tumor circumference can serve as an important predictor of pathological tumor response. This was demonstrated in the study by Das et al. [11]. In this study, the results of the univariate and multivariate analysis indicate that the circumferential extent of tumor (less than 60%) predicts significantly the complete response rate and downstaging. These results agree with those of our study, the circumferential extent of a tumor was significantly predicted for PCR and downstaging with a p of 0.001 and 0.007 respectively.

The interval from the end of radiation to surgery has been of special interest and has been directly addressed by multiple studies as well as a meta-analysis [12]. Although the exact ideal interval to optimize PCR has not been identified, the overall conclusion from these studies is that PCR rates improve with delaying surgery by more than 6–8 weeks after the end of RCT. In this context, curative surgical treatments performed at six weeks from the end of the RCT may have interrupted ongoing necrosis, which means that some patients may achieve complete tumor regression if waiting times were longer [13]. Kalady et al. in 2009 [14] had shown that interval ≥ 8 weeks between treatment completion and surgical resection was significantly associated with a higher rate of PCR (p = 0.03). A study by D. A. M. Sloothaak et al. in 2013 [15]. showed that Delaying surgery until 10-11 weeks after the end of RCT was significantly correlated with the complete histological response (p = 0.013). A recently published study using NCDB data provided the largest dataset focusing on the question of the interval from the end of CRT to surgery, and concurred with the published literature that an interval of more than 8 weeks is associated with increased rates of complete response [16]. In our study, the time between RCT and surgery was not correlated with a complete response (p = 0.3). However, a delay of ≥ 8 weeks was a predictor of downstaging (p = 0.02). These findings are consistent with other recent studies, where they observed more downstaging and better surgical results with a delay of more than 8 weeks [17]. The largest published dataset to date [18], dealing with predictive factors of PCR after preoperative RCT in 23747 patients with rectal cancer, is consistent with those findings but, furthermore, offer additional variables that can help identify those patients most likely to respond (lower tumor grade, lower clinical T and N stage and higher radiation dose, while lack of health insurance was linked with a lower likelihood of PCR). Other studies have reported some variables that were not included in this study, such as low pretreatment CEA level [19-24], low CEA level after RCT [25, 26], small pre- [27, 28] and post-treatment tumor size [29], pre-treatment tumor mobility on digital rectal examination [29], low clinical lymph node (N) classification [27], low tumor grade [30, 31], shorter distance from the anal verge [11, 30] , low neutrophil to lymphocyte ratio [28], type of concurrent chemotherapy used [32] and higher radiation dose [33]. These factors are subjective parameters that are susceptible to inter-observer variations, and it is difficult to assess these factors in a retrospective study.

In conclusion, the identification of predictive factors for tumor response could have potential therapeutic applications. The increase in the rates of complete or partial histological responses has led to the emergence of the concept of conservative approaches such as a wait-and-see strategy [34]. Further studies are required to determine strategies for optimizing the oncological outcome on an individual basis.