ISR was originally classified as subtotal and total according to the partial or complete resection of the IAS [18]. However, the Japanese experience on ISR has modified the original classification into three types (Figure 1) [41,42]: (1) Total ISR (complete removal of the internal anal sphincter at the intersphincteric groove); (2) Subtotal ISR (the resection line lays between the dentate line (DL) and the intersphincteric groove (ISG); (3) Partial ISR (the resection is at the level of the DL. The choice of the dissection line depends on the lower border of the tumor in order to obtain an adequate distal clearance (distal resection margin (DRM) ≥ 1 cm).

The intersphincteric dissection for ISR is usually started in the transabdominal phase and completed during the perineal phase [19,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57]. However, some authors perform the intersphincteric dissection in toto only during the perineal phase [58,59,60,61,62,63,64,65,66]. Park et al. and Kim et al. have reported the use of the robotic platform to perform total/near-total single-stage transabdominal ISR with no need for a perineal intersphincteric dissection [67,68].

ISR is a surgical technique for treating patients with LRC, generally defined as tumors with the caudal edge within 4–5 cm from the anal verge (AV) or 2 cm above the DL. Surgical indications for ISR have changed since the standardization of the technique [18] (Table 1). However, a precise preoperative staging with the combination of rectal MRI, thoracic-abdominopelvic computed tomography (CT) scan, anal EUS, rigid proctoscopy, and digital rectal examination (DRE) remains crucial for a correct surgical indication [69]. Restaging should be done after neoadjuvant chemoradiation (nCRT), and surgical indications must be always re-checked and re-discussed with the patient. The final decision to perform an ISR or convert to APR is done by the surgeon in the operating theatre, before starting surgery, while performing DRE under anesthesia to access tumor mobility and relationship to the anal sphincters [49,60].

The reviews of Martin et al. [69], Akagi et al. [41], and Shirouzu et al. [70] have critically discussed the indication criteria for ISR. They all agreed that ISR should be indicated for well/moderately differentiated T1–3 tumors located within 5 cm from the AV, independently to IAS invasion. Poorly differentiated, T4, fixed tumors (at DRE), with EAS/LAM infiltration and/or untreatable distant metastases should be contraindicated to ISR. Moreover, ISR should not be indicated to patients with poor anal function, severe preoperative pathologies (cardiac failure, liver cirrhosis, renal dysfunction, and respiratory dysfunction), or psychiatric disease. These indications were confirmed by a national-based questionnaire from the Japanese Society for Cancer of the Colon and Rectum (JSCCR) [71].

Rullier et al. implemented the indication criteria for LRC, through an MRI-based classification [72]. They classified LRC into four types to assist decision-making between anus-preserving surgery and APR. Type I are LRC defined as supra-anal tumors (lesions >1 cm from the anorectal ring). Type II are defined as juxta-anal tumors (lesions ≤ 1 cm from the anorectal ring). Type III are defined as intra-anal tumors (lesions with IAS invasion). Type IV are defined as transanal tumors (lesions with EAS or LAM invasion). They indicated ISR for type II and III. Furthermore, some authors have proposed to combine ISR with partial resection of the EAS for type IV tumors [42,73,74]. Rullier’s classification is very intuitive and of easy use, however, it evaluates the tumor position, from MRI images, in relation to the LAM and EAS in a frontal view without considering the circumferential position of the tumor on the anal clock. Through a retrospective analysis of surgical specimens, Kang et al. analyzed the circumferential tumor location, reporting that the anterior aspect most frequently involves the circumferential resection margin (CRM) and exhibits a deeper tumor invasion [75]. Further studies are needed to define if the circumferential tumor location may in the future play a role in the treatment strategy, such as stronger indication for preoperative radiotherapy or choice of surgical approach.

The indication criteria for ISR have been recently discussed by two studies. Park et al. [56] have examined the role of the tumor’s response to nCRT on restaging pelvic MRI as indication criteria for ISR. They reported the ymrT stage and ymrCRM status as key factors for deciding between ISR and APR. Moreover, ISR indication was extended also to patients with cT4 LRS that downstaged after CRT (i.e., ymrT0–3). Poor responders (i.e., ymrT3) with suspicious tumor invasion of the CRM should instead undergo APR.

Piozzi et al. reported a study on 161 ISR where indication criteria were extended. In this study patients with post nCRT clearance of EAS/LAM infiltration were indicated to ISR independently to T stage if curative resection was considered technically feasible at the pre-operative MRI staging [57].

Clinical indications to ISR have changed in the last three decades however an international consensus should be taken to critically define them in order to perform standardized ISR with comparable results throughout the colorectal community.