This retrospective study was based on the clinical data of LARC patients treated at our center. Patients were eligible for this study if they met the following criteria: pathologically confirmed rectal adenocarcinoma (biopsy), the tumor located less than or equal to 8 cm from the anal verge on colonoscopy or MRI, pre-treatment MRI scan with a diagnosis of cT3-4 or N-positive disease, absence of DM on abdominopelvic and chest computed tomography (CT) scans, Eastern Cooperative Oncology Group performance status of 0–1, age ≥ 18 years, absence of any serious medical comorbidities or any other cancers, completed NCRT with good compliance and follow-up assessments.

All patients were informed the risks and benefits of NCRT and signed informed consent before treatment. This study was approved by the institutional review board of the Beijing Cancer Hospital Ethics Committee (approval number: 2020YJZ71) and was conducted according to the Declaration of Helsinki.

All patients underwent pelvic MRI scanning before NCRT, and the sequence of scans included axial, axial oblique, coronal, and sagittal T2-weighted and diffusion-weighted images [24]. All MRI scans were evaluated by one senior radiologist and one radiation oncologist. The T/N stage, T3 subgroup, EMVI, and MRF status were recorded according to the ESMO guidelines. The LPLN areas were defined as the lymph node located in the internal iliac and obturator lymphatic drainage areas, all lymph nodes visible in those areas were evaluated, including short diameter, margins, and signal values. The criteria of positive LPLN were short diameter more than or equal to 7 mm combined with irregular margin and mixed signal findings [16, 25]. Patients were divided into LPLN-positive and LPLN-negative groups based on the LPLN status.

About 4–8 weeks after NCRT, repeat MRI scans were acquired to re-evaluate MRF, EMVI status and T/N stage, and to provide a reference for subsequent surgery. Lateral pelvic lymph nodes were re-evaluated to determine the suitability of LPLD [26]. For patients undergoing non-surgical treatments after NCRT, MRI scanning was used as a routine part of follow-up assessments.

All patients underwent computed tomography (CT) scan simulation after filling the bladder. Thermoplastic membrane and abdominal plate board, supine position, enhanced CT scanning, and MRI scan simulation were used. All patients were recommended intensity-modulated radiotherapy (IMRT), and most patients underwent simultaneous integrated boost (SIB) technique. The target area outline was previously described in recent study [27]. Briefly, the primary gross tumor volume (GTVp) contained the primary rectal tumor and enlarged lymph nodes in the rectal mesentery, and clinical target volume (CTV) contained the primary tumor and anterior sacral area, rectal mesenteric area, and internal iliac and obturator lymphatic drainage areas. These target areas were expanded by 5 mm to form planing primary gross tumor volume (PGTVp) and planning target volume (PTV). The total radiation doses were 50–50.6 Gy/22–25 F and 41.8–45 Gy/22–25 F delivered to PGTVp and PTV. For the patients with positive LPLN, gross lymph node tumor volume (GTVn) was outlined, and the planning gross lymph node tumor volume (PGTVn) was the GTVn with a 5-mm margin. The dose delivered to PGTVn was 56–60 Gy/22–25 F, this radiation therapy dose began to apply since 2016, at 2019 this dose strategy was used for all positive LPLN patients who receiving NCRT in our hospital.

Synchronous chemotherapy included oral capecitabine with or without oxaliplatin. The dose of capecitabine was 825 mg/m2 twice daily for 5 days/week; when combined with oxaliplatin therapy, the dose of oxaliplatin was 85 mg/m2 for every 2 weeks.

Post-surgery, all patients were recommended to receive adjuvant chemotherapy. Chemotherapy regimens included CapOX, FOLFOX, or oral capecitabine. The specific adjuvant chemotherapy regimen is based on the recommendations of a multidisciplinary consultation. We recommend 10 cycles or more for biweekly chemotherapy regimens and 6 cycles or more for three-weekly chemotherapy regimens, and 6 months of oral administration for single agent capecitabine.

The results of several recent studies indicated that the addition of chemotherapy prior to surgery improves pathologic complete response (pCR) rate [28, 29], based on these results and the strong desire of some patients to preserve their anus, we have adopted a treatment plan of concurrent chemoradiotherapy combined with induction or consolidation chemotherapy with a regimen of CapOX (oxaliplatin 130 mg/m2, d1; capecitabine 1000 mg/m2 twice daily, d1-14/Q21d).

At approximately 5–12 weeks after NCRT, patients were recommended to receive surgery if imaging and clinical examination findings revealed no contraindications. Radical surgery was performed following the TME principle, surgical procedures included low anterior resection, abdominoperineal resection, and Hartmann procedure. LPLD was recommended for patients whose short LPLNs were still greater than 5 mm after NCRT. Intentional watch & wait strategy can be used for those who have been critically evaluated for complete clinical response and do not wish to undergo surgery. If the patient's staging is assessed as ycT0-2N0 and they have a strong desire to preserve their anus, local excision may be considered.

Surgical specimens were evaluated by specialized pathologists. A structured pathology report was issued, the report including tumor volume, upper and lower margins, circumferential margins, T/N stage, number and location of metastatic lymph nodes, presence of cancer nodes, presence of vascular thrombi and nerve invasion, and tumor regression grade (assessed according to the AJCC criteria) [2]. R0 resection was confirmed when the outer edge of the tumor or positive lymph node was more than 1 mm from the circumferential resection margin and both upper and lower margins were negative [30].

During NCRT, all patients were recommended weekly outpatient visits to assess and manage toxicities, which were graded based on the Common Terminology Criteria of Adverse Events Version 4.0.

Subsequently, patients were recommended to undergo follow-up visits every 3 months for the first 2 years, every 6 months for the subsequent 3 years and then yearly thereafter. Follow-up assessments included medical history taking, chest and abdominopelvic CT, serum carcinoembryonic antigen, and colonoscopy if necessary. As required, digital rectal examination, colonoscopy and MRI were performed for patients who had undergone non-surgical treatments.

The primary outcome was progression-free survival (PFS), which accounted for local regional recurrence (LRR) and distant metastases (DM). PFS was measured from the end of NCRT to the date of any evidence of progression or death from any cause or the last follow-up. The oligometastases were defined the amount of metastatic lesions was one to five [31]. DM were divided into oligometastases and non-oligometastases, and DM were observed from the end of NCRT to the date of any evidence of DM confirmed by radiology or pathology findings. LRR was divided into lateral pelvic recurrence and other local recurrence type, LRR was observed from the end of NCRT to the date of any evidence of recurrence.

The patients’ clinical and follow-up characteristics were recorded. All statistical analyses were performed in Statistical Package for the Social Sciences (IBM Corp. SPSS Statistics for Windows, v.22.0, Armonk, NY, USA). The chi-square test was used to compare the groups. Propensity score matching (PSM) was used to balance group characteristics and was performed in Statistics and Data Science (STATA Corp. STATA for Windows, v.17.0, Texas, USA). Clinically relevant variables included tumor location, tumor length, tumor thickness, T/N stage, MRF status, and EMVI status. The caliper width was equal to 0.1 of the logit standard deviation of the propensity score. Survival curves were generated using the Kaplan–Meier method and were compared by using the log-rank test. P-values of < 0.05 were considered indicative of statistically significant findings.