Aims: Selective lateral pelvic lymph node (LPN) dissection (LPND) following neoadjuvant chemoradiotherapy (nCRT) for rectal cancer is widely recognized. This study aimed to determine the effects of nCRT before LPND on local control and prognosis of rectal cancer patients. Materials and methods: Data were retrieved from a prospective database for rectal cancer patients with clinical LPN metastasis receiving total mesorectal excision and LPND at three institutions between January 2012 and December 2019. Selection bias was minimized using propensity score matching (PSM) and short-term and clinical outcomes were compared. Results: Patients (n = 213) were enrolled and grouped as either nCRT (n = 97) or non-nCRT (n = 116). PSM was used to identify 83 matched pairs. In the matched cohort, nCRT patients had a longer operation duration (310.6 vs. 265.0 min, P = 0.001), lower pathological LPN metastasis rate (32.5% vs. 48.2%, P = 0.040), and fewer harvested lymph nodes (22 vs. 25, P = 0.018) compared to the non-nCRT group. However, after PSM, the two groups had similar estimated overall 3-year survival (79.5% vs. 80.7%, P = 0.922), 3-year disease-free survival (66.1% vs. 65.5, P = 0.820), and 3-year local recurrence-free survival (88.6% vs. 89.7%, P = 0.927). Distant metastasis was the predominant recurrence pattern in the overall (45/58, 77.6%) and matched (33/44, 75.0%) cohorts. Conclusions: LPND without nCRT is effective and sufficient in preventing local recurrence in patients with LPN metastases. Future prospective randomized controlled studies are warranted to confirm these findings. Since systemic metastasis is the predominant recurrence pattern in patients with LPN metastasis post-LPND, improved perioperative systemic chemotherapy is needed to prevent micrometastasis.
Keywords: Neoadjuvant chemoradiotherapy; Lateral pelvic lymph node dissection; Local control; Prognosis; Safety
Zhongshi Xie and Qichen Chen contributed equally to this work.
Total mesorectal excision (TME) is a common radical procedure for removing rectal tumors. However, between 10 and 25% of patients with advanced middle-to-lower rectal cancer experience recurrence in the lateral pelvic lymph node (LPN), which is a major site of recurrence following the TME procedure [[
LPND and nCRT have gradually converged, and selective LPND following nCRT can eradicate residual lymph nodes while avoiding unnecessary treatment in rectal cancer patients who have reached pathologically complete responses following nCRT [[
Data were retrieved for rectal cancer patients (n = 485) with LPN metastasis who received TME and LPND at three institutions from the Chinese Lateral Node Collaborative Group between January 2012 and December 2019 from a prospective database and tumor registry. The Cancer Hospital of the Chinese Academy of Medical Sciences served as the initiator of the study, and the ethics committee of Cancer Hospital, Chinese Academy of Medical Sciences approved this study (NCC 2017-YZ-026, Oct 17, 2017). Patients provided informed consent and all procedures were performed in agreement with the World Medical Association and the Declaration of Helsinki. The study protocol was registered (20/04/2021, NCT04850027) at ClinicalTrials.gov.
The inclusion criteria consisted of (
Graph: Fig. 1Grouping and PSM flowchart. TME, total mesorectal excision; LPND, lateral pelvic lymph node dissection; nCRT, neoadjuvant chemoradiotherapy; PSM, propensity score matching; LPN, lateral pelvic lymph node; MRI, magnetic resonance imaging; BMI, body mass index; ASA, American Society of Anesthesiologists; LN, lateral lymph node
Clinical TNM staging and LPN metastases in this study were evaluated and diagnosed by two radiologists using computed tomography (CT) and MRI, where diagnoses met the following three criteria and could be defined as high-level evidence of LPN metastasis: (
The patients' treatment approaches, including the surgical approach (e.g., laparoscopic vs. open) and the decision to perform nCRT, were decided by the patient in consultation with a multidisciplinary team (MDT) comprised of medical and surgical oncologists and radiologists. Among patients with mesorectal fascial (MRF) involvement, multiple lymph node metastases, or a strong desire to preserve the sphincter in ultra-low rectal carcinomas, nCRT was considered and recommended. Furthermore, the treatment strategy for LPN metastases was updated during the study period. Between 2012 and 2017, upfront surgery without nCRT was performed in patients with LPN metastasis After 2018, patients with LPN (≥ 10 mm diameter) underwent nCRT before LPND. These patients received chemotherapy and radiation (capecitabine and 50.4 Gy in 28 fractions) targeting the LPN basin, and TME + LPND was performed 6–8 weeks following nCRT. All patients received LPND after nCRT, regardless of the degree of tumor regression. Adjuvant chemotherapy was administered 4–8 weeks after surgery, including XELOX, mFOLFOX6, or single-agent capecitabine. Patients in the nCRT group underwent adjuvant chemotherapy regardless of the pathological stage, along with six months of perioperative chemotherapy. In the non-nCRT group, high-risk patients in stages II and III (pT4, poor differentiation, tumor perforation, and lymphatic and perineural invasion) received adjuvant chemotherapy after surgery. In addition, patients with pathological LPN metastasis, N2 stage, CRM ≤ 1 mm, and positive margins in the non-nCRT group were recommended to receive chemoradiation (45.0–54.0 Gy in 25–28 fractions, including LPN basin) in addition to chemotherapy.
In this study, the chief surgeons in each institution performed laparoscopic colorectal surgery at least 500 times, and at least 100 cases of LPND were completed. Dissection was performed unilaterally or bilaterally depending on the LPN metastasis location assessed by MRI before treatment. As previously described [[
During the first three years, patients were examined every three months; after that, they were examined twice a year. Each follow-up entailed a physical examination, assessment of tumor markers, and CT evaluation of the abdomen, chest, and pelvis. A total endoscopy was performed every year. Oncological outcomes were determined by three-year overall survival (OS), recurrence-free survival (RFS), and local RFS (LRFS). Tumor return in the pelvic cavity was considered local recurrence and classified as central (anastomotic, anterior, perineal, or presacral) or lateral, while tumor growth outside the pelvic cavity was considered distant metastasis.
PSM was employed to match patients in the nCRT and non-nCRT groups (caliper = 0.2) to reduce the imbalance. Imbalances were selected based on observations in the original cohort and known potential confounding variables including gender, age, body mass index (BMI), CEA levels, assigned American Society of Anesthesiologists category, surgical approach, types of operation, distance from the anal verge, histology clinical T stage, clinical mesenteric lymph node status, unilateral or bilateral LPND, and adjuvant therapy. These variables were factored into bivariate logistic regression and used to calculate patients' propensity scores.
Continuous variables were compared by Student's t-test or Mann–Whitney U test and presented as mean ± standard deviation or as median (range) if assumptions of normal distribution were violated. Categorical variables were compared using the Chi-square test and presented as values (%). The Kaplan–Meier method calculated three-year cumulative OS, RFS, and LRFS. A univariate analysis was performed and assessed using the log-rank test, and when the results were significant, they were subsequently modeled by Cox regression. A P-value of < 0.05 was considered significant. Statistical analysis was performed using SPSS v.24.0 (IBM Inc., Armonk, NY, USA).
Table 1 lists the demographic and clinical data before and after PSM. Before PSM, a greater proportion of patients in the nCRT group had ASA grade III (8.3% vs. 1.7%, P = 0.027), moderate differentiation (78.4% vs. 65.5%, P = 0.039), laparoscopic surgery (91.8% vs. 81.0%, P = 0.025), and mesorectal fascial involvement (9.3% vs. 0, P = 0.001) than patients in the non-nCRT group. After matching, the variables were not different between groups (P > 0.05). Additionally, 65 (78.3%) patients in the nCRT group received adjuvant chemotherapy, 51 (61.4%) patients in the non-nCRT group received adjuvant chemotherapy, and 10 (12.1%) patients received adjuvant chemoradiation in addition to chemotherapy.
Table 1 Demographic data and clinical characteristics before and after propensity score matching
Variables Original cohort Matched cohort nCRT ( Non-nCRT ( nCRT ( Non-nCRT ( Age (years, mean ± SD) 55.0 ± 11.8 57.6 ± 11.1 0.097 55.6 ± 11.5 57.3 ± 11.2 0.358 Gender 0.650 0.874 Male 59 (60.8) 67 (57.7) 50 (60.2) 49 (59.0) Female 38 (39.2) 49 (42.3) 33 (39.8) 34 (41.0) BMI (kg/m2, mean ± SD) 24.7 ± 3.3 24.1 ± 3.3 0.254 24.6 ± 3.2 24.5 ± 3.3 0.935 ASA category 0.027 1.000 I-II 89 (91.7) 114 (98.3) 81 (97.6) 82 (98.8) III 8 (8.3) 2 (1.7) 2 (2.4) 1 (1.2) Distance from anal verge, median (range) cm 4 (1–8) 4 (1–8) 0.113 4 (1–8) 4 (1–8) 0.486 CEA level (ng/ml) 0.654 0.751 ≥5 41 (42.3) 51 (44.0) 32 (38.6) 34 (41.0) <5 46 (57.7) 65 (56.0) 51(61.4) 49 (59.0) LPN short-diameter before nCRT (cm, mean ± SD) 1.3 ± 0.6 1.1 ± 0.5 0.103 1.2 ± 0.5 1.2 ± 0.6 0.930 Surgical approach 0.025 0.787 Open 8 (8.2) 22 (19.0) 7 (8.4) 8 (9.6) Laparoscopic 89 (91.8) 94 (81.0) 76 (91.6) 75 (90.4) Histology 0.039 0.222 Moderate 76 (78.4) 76 (65.5) 64 (77.1) 57 (68.7) Poor/Mucinous/signet 21 (21.6) 40 (34.5) 19 (22.9) 26 (31.3) Clinical T stage 0.107 0.755 T1 -T2 5 (5.2) 8 (6.9) 5 (6.0) 6 (7.2) T3-T4 92 (94.8) 108 (93.1) 78 (94.0) 77 (92.8) Clinical Mesenteric LN status 0.191 0.360 Positive 85 (87.6) 94 (81.0) 66 (79.5) 61 (73.5) Negative 12 (12.4) 22 (19.0) 17 (20.5) 22 (26.5) (y) Clinical T stage - - T1-T2 26 (26.8) - 25 (30.1) - T3-T4 71 (73.2) - 58 (69.9) - (y) Clinical Mesenteric LN status - - Positive 54 (55.7) - 50 (60.2) - Negative 43 (44.3) - - 33 (39.8) - LPN short-diameter after nCRT (cm, mean ± SD) 0.7 ± 0.4 - 0.7 ± 0.3 - - Type of operation 0.792 0.759 LAR 44 (45.3) 60 (51.7) 38 (45.8) 40 (48.2) APR 44 (45.3) 48 (41.4) 37 (44.6) 38 (45.8) Hartmann procedure 6 (6.2) 5 (4.3) 5 (6.0) 4 (4.8) TPE 3 (3.1) 3 (2.6) 3 (3.6) 1 (1.2) LPND 0.473 0.310 Bilateral 32 (33.0) 33 (28.4) 28 (33.7) 22 (26.5) Unilateral 65 (67.0) 83 (71.6) 55 (66.3) 61 (73.5) Adjuvant therapy 79 (81.4) 85 (73.3) 0.158 65 (78.3) 61 (73.5) 0.468 Chemotherapy 79 (81.4) 73 (63.0) 65 (78.3) 51 (61.4) Chemoradiation + chemotherapy 0 (0) 12 (10.3) 0 (0) 10 (12.1) Mesorectal fascial involvement 0.001 0.245 Yes 9 (9.3) 0 (0) 2 (2.4) 0 (0) No 88 (90.7) 116 (100.0) 81 (97.6) 83 (100.0)
Note: nCRT, neoadjuvant chemoradiotherapy; BMI, body mass index; ASA, American Society of Anesthesiologists; LN, lymph node; LAR, low anterior resection; APR, abdominal perineal resection; TPE, total pelvic exenteration; LPND, lateral pelvic lymph node dissection; SD, standard deviation
Surgical outcomes and complications are presented in Table 2. There was a longer operative time for the nCRT group than the non-CRT group after PSM (310.6 vs. 265.0 min, P = 0.001), but estimated blood loss during surgery did not differ (50 vs. 50 ml, P = 0.281). The groups did not have differences in terms of grade 1–5 (21.7% vs. 14.5%, P = 0.226) and grade 3–5 (9.6% vs. 8.4%, P = 0.787) postoperative complications. After matching, the two groups of patients had similar postoperative hospital stays (11.6 vs. 10.9 d, P = 0.626), and no perioperative deaths were reported.
Table 2 Surgical outcomes and pathological results before and after propensity score matching
Variables Original cohort Matched cohort nCRT ( Non-nCRT ( nCRT ( Non-nCRT ( Operative time (min, mean ± SD) 306.1 ± 90.9 281.3 ± 102.2 0.048 310.6 ± 95.8 265.0 ± 79.5 0.001 Estimated blood loss, median (range) ml 50 (10 − 1,700) 50 (10 − 2,500) 0.329 50 (10 − 1,700) 50 (10 − 1,100) 0.281 Postoperative complications (Grade 1–5) 20 (20.6) 18 (15.5) 0.333 18 (21.7) 12 (14.5) 0.226 Postoperative complications (Grade 3–5) 9 (9.3) 10 (8.6) 0.867 8 (9.6) 7 (8.4) 0.787 Mortality 0 (0) 1 (0.9) 1.000 0 (0) 0 (0) 1.000 Postoperative hospital stay (days, mean ± SD) 11.2 ± 9.5 12.9 ± 10.0 0.208 11.6 ± 10.2 10.9 ± 7.4 0.626 (y) Pathological T stage < 0.001 < 0.001 T0 -T2 31 (31.9) 14 (12.1) 28 (33.7) 7 (8.4) T3-T4 66 (68.1) 102 (87.9) 55 (66.3) 76 (91.6) (y) Pathological mesenteric LN status 0.001 0.003 Positive 45 (46.4) 81 (69.8) 38 (45.8) 57 (68.7) Negative 52 (53.6) 35 (30.2) 45 (54.2) 26 (31.3) PCR rate 10 (10.3) - - 9 (10.8) - - Down T staging rate 64 (65.9) - - 58 (69.9) - - Down N staging rate 70 (72.2) - - 63 (75.9) - - Pathological LPN metastasis 30 (30.9) 57 (49.1) 0.007 27 (32.5) 40 (48.2) 0.040 Total LNs harvested, median (range) 22 (6–62) 26 (7–77) 0.042 22 (6–62) 25 (8–77) 0.018 LPNs harvested, median (range) 8 (1–16) 8 (1–17) 0.652 8 (1–16) 7 (1–15) 0.244 Circumferential Resection Margin 0.593 1.000 Positive 2 (2.1) 1 (0.9 1 (1.2) 0 (0) Negative 95 (97.9) 115 (99.1) 82 (98.8) 83 (100.0)
Note: nCRT, neoadjuvant chemoradiotherapy; SD, standard deviation
Pathological results pre- and post-PSM are presented in Table 2. In the matched cohort, the rates of pathological complete response (PCR), down T staging, and down N staging after nCRT, were 10.8%, 69.9%, and 75.9%, respectively. There was a lower rate of pathological LPN metastasis in the nCRT group compared with the non-nCRT group (32.5% vs. 48.2%, P = 0.040). nCRT significantly reduces the amount of harvested lymph nodes (22 vs. 25, P = 0.018). No difference in the positive circumferential resection margin (1.2% vs. 0, P = 1.000) was observed between groups.
The mean follow-up periods for the nCRT versus non-nCRT groups were 38.8 and 37.0 months, respectively, in the overall cohort, and 38.1 and 36.2 months, correspondingly, in the matched cohort. Before PSM, the two groups did not differ in the estimated three-year OS (78.7% vs. 76.2%, P = 0.662), three-year RFS (65.8% vs. 60.5, P = 0.718), and three-year LRFS (89.5% vs. 84.6%, P = 0.418) (Fig. 2). Similarly, there were no differences in the estimated three-year OS (79.5% vs. 80.7%, P = 0.922), three-year RFS (66.1% vs. 65.5, P = 0.820), and three-year LRFS (88.6% vs. 89.7%, P = 0.927) between the two groups after PSM (Fig. 3).
Graph: Fig. 2OS curve, RFS curve, and LRFS curve for patients in the nCRT and non-nCRT groups before PSM. OS, overall survival; RFS, recurrence-free survival; LRFS, local recurrence-free survival; nCRT, neoadjuvant chemoradiotherapy; PSM, propensity score matching
Graph: Fig. 3OS curve, RFS curve, and LRFS curve for patients in the nCRT and non-nCRT groups after PSM. OS, overall survival; RFS, recurrence-free survival; LRFS, local recurrence-free survival; nCRT, neoadjuvant chemoradiotherapy; PSM, propensity score matching
In addition, Table 3 shows recurrence patterns up to three years after surgery in both groups before and after PSM. Before PSM, the proportion of local recurrences (9.3% vs.12.1%, P = 0.513) and distant recurrences (19.6% vs. 22.4%, P = 0.615) was comparable between the nCRT and non-nCRT groups. After PSM, both groups had a similar proportion of local recurrences (9.6% vs.8.4%, P = 0.787) and distant recurrences (20.5% vs. 19.3%, P = 0.846). It is worth noting that whether in the overall cohort (45/58, 77.6%) or the matched cohort (33/44, 75.0%), the predominant recurrence was distant metastasis.
Table 3 Recurrence pattern up to three years after surgery before and after propensity score matching
Variables Original cohort Matched cohort nCRT ( Non-nCRT ( nCRT ( Non-nCRT ( Overall recurrence 26 (26.8) 32 (27.6) 0.898 23 (27.7) 21 (25.3) 0.725 Local recurrence 9 (9.3) 14 (12.1) 0.513 8 (9.6) 7 (8.4) 0.787 Central pelvic 6 (6.2) 10 (8.6) 5 (6.0) 6 (7.2) Lateral pelvic 4 (4.1) 6 (5.2) 3 (3.6) 3 (3.6) Distant metastasis 19 (19.6) 26 (22.4) 0.615 17 (20.5) 16 (19.3) 0.846 Lung 12 (12.4) 15 (12.9) 10 (12.0) 11 (13.3) Liver 10 (10.3) 11 (9.5) 9 (10.8) 8 (9.6) Bone 6 (6.2) 8 (6.9) 5 (6.0) 5 (6.0) Peritoneum 1 (1.0) 3 (2.6) 1 (1.2) 2 (2.4) Lymph node 1 (1.0) 2 (1.7) 1 (1.2) 2 (2.4)
Note: nCRT, neoadjuvant chemoradiotherapy
Prognostic factors influencing RFS and LRFS in the overall cohort identified by univariate and multivariate analyses are shown in Table 4. For the univariate analyses, histology, operative type, lymphatic invasion, pathological mesorectal LN metastasis, pathological LPN metastasis, and grade 3–4 postoperative complication influenced RFS and LRFS (P < 0.05). The pathological T stage also influenced LRFS (P < 0.05). For the multivariate analyses, pathological LPN metastasis (HR: 3.11; 95% CI: 1.68–5.77, P < 0.001) and pathological mesorectal LN metastasis (HR: 4.16; 95% CI: 1.76–9.87, P = 0.001) were revealed as independent prognostic factors for RFS and LRFS, respectively.
Table 4 Univariate and multivariate analyses for DFS and LRFS in the overall cohort
Variables RFS LRFS Univariate analysis Multivariate analysis Univariate analysis Multivariate analysis HR (95%CI) HR (95%CI) HR (95%CI) HR (95%CI) Gender: male/female 1.11 (0.65–1.91) 0.704 0.93 (0.47–1.85) 0.843 Age at operation 0.99 (0.96–1.01) 0.258 0.98 (0.95–1.01) 0.270 ASA score: I-II/III 2.53 (0.35–18.28) 0.359 1.45 (0.20-10.64) 0.713 Pre-nCRT CEA level (≥ 5/<5 ng/ml) 1.12 (0.65–1.91) 0.682 1.19 (0.60–2.36) 0.622 Neoadjuvant chemoradiotherapy (yes/no) 0.86 (0.51–1.48) 0.718 1.30 (0.73–2.33) 0.370 0.81 (0.41–1.62) 0.662 1.24 (0.61–2.54) 0.552 Histology (Poor, Mucinous or signet/moderate) 2.72 (1.29–5.77) 0.009 1.24 (0.57–2.72) 0.587 3.57 (1.26–10.09) 0.017 1.17 (0.42–3.25) 0.761 Operative type: laparoscopic/open 0.37 (0.21–0.66) 0.001 0.56 (0.29–1.09) 0.088 0.36 (0.18–0.73) 0.004 0.65 (0.29–1.46) 0.292 Lymphatic invasion (yes/no) 5.12 (2.64–9.20) < 0.001 1.33 (0.57–3.10) 0.508 4.91 (1.61–14.93) 0.005 2.38 (0.88–6.44) 0.089 Perineural invasion (yes/no) 1.24 (0.65–2.36) 0.516 2.44 (0.95–7.42) 0.088 Pathological T stage (T3-T4/T1-T2) 1.84 (0.90–3.77) 0.094 2.89 (1.02–8.24) 0.047 1.77 (0.59–5.32) 0.311 Pathological mesorectal LN status (positive/negative) 3.00 (1.51–5.96) 0.002 1.70 (0.79–3.65) 0.174 5.93 (2.67–13.18) < 0.001 4.16 (1.76–9.87) 0.001 Pathological LPN metastasis (yes/no) 4.00 (2.28–7.02) < 0.001 3.11 (1.68–5.77) < 0.001 4.56 (1.60-12.98) 0.004 2.00 (0.65–6.17) 0.228 Postoperative complication (yes/no) 1.39 (0.43–4.47) 0.578 2.70 (0.82–8.91) 0.103 Grade 3–4 Postoperative complication (no/yes) 1.84 (1.01–3.38) 0.049 1.71 (0.92–3.20) 0.093 2.25 (1.07–4.73) 0.033 2.12 (0.87–4.61) 0.058 Adjuvant therapy (yes/no) 1.36 (0.52–4.89) 0.542 2.31 (0.45–9.32) 0.635
Note: RFS, recurrence-free survival; LRFS, local recurrence-free survival; HR, hazard ratio; 95%CI, 95% confidence interval; ASA, American Society of Anesthesiologists, nCRT, neoadjuvant chemoradiotherapy; CEA,; LN, lymph node; LPN, lateral pelvic lymph node
As stated previously, for the management of LPN metastasis, there is no consensus between Japanese and Western countries, and nCRT and LPND are mutually exclusive treatments. In recent years, the treatment strategy of selective LPND after nCRT has been recognized and supported, and the indications of selective LPND after nCRT have been gradually established [[
There is controversy over LPND because it is technically difficult to perform and the pelvic sidewall is anatomically complex. nCRT may not only cause tissue edema and fibrosis, which makes LPND even more difficult to perform but also potentially inhibits the immune system and increases the risk of infection at the incision site and in the lung and pelvis [[
The amount of lymph nodes dissected is important to consider when evaluating the quality of surgery and determining prognosis [[
nCRT resulted in satisfactory therapeutic effects, with a PCR rate of 10.8%, a down T staging rate of 69.9%, and a down N staging rate of 75.8% in the matched cohort, consistent with those reported previously [[
Our study demonstrated no significant improvements in three-year OS (79.5% vs. 80.7%, P = 0.922), three-year RFS (66.1% vs. 65.5, P = 0.820), and three-year LRFS (88.6% vs. 89.7%, P = 0.927) between the nCRT and non-nCRT groups. We investigated the postoperative recurrence patterns and the primary cause of treatment failure as distant metastasis [overall cohort: 77.6% (45/58); matched cohort: 75% (33/44)], suggesting that patients with LPN metastasis were in the advanced stages and tended to develop systemic metastasis. In recent years, the concept of a multidisciplinary comprehensive treatment strategy has positively improved the prognosis for patients with LPNM. Since nCRT is less effective in reducing the risk of systemic metastasis for rectal cancer patients, adjuvant chemotherapy is needed to eliminate potential micro-metastases [[
Our study has several limitations that need consideration. First, we did not analyze urinary and sexual dysfunction, the major postoperative complications related to LPND. Therefore, the safety of LPND after nCRT cannot be completely measured and reflected. Second, this study was retrospective, participants were not randomized, and we could not preclude the possibility of selection bias. A small proportion of patients in the non-nCRT group received adjuvant chemoradiation in addition to chemotherapy, which could interfere with the analysis of the results between the two groups. Furthermore, as clinical LPN metastasis might be over-staged based on preoperative MRIs, the demographic characteristics and clinical staging were different between the CRT and non-CRT groups. However, the same diagnostic criteria for LPN metastasis were used for both groups, while performing PSM to reduce selection bias; data before and after PSM were retained, reflecting the outcomes of nCRT for LPN metastasis in China. Third, because this study spanned 8 years, only 45.5% (97/213) of patients with clinical LPNM underwent nCRT, and this figure may not be consistent with that for the conventional treatment strategies. A prospective, randomized study will help to further confirm the oncological effect of performing nCRT before LPND in patients with LPN metastasis.
In summary, LPND without nCRT is effective and sufficient in preventing local recurrence for patients with LPN metastases, and randomized controlled trials are further warranted. Since systemic metastasis is the predominant recurrence in patients with LPN metastasis following LPND, improved perioperative systemic chemotherapy is needed to prevent micro-metastasis.
The study protocol was registered (20/04/2021, NCT04850027) at ClinicalTrials.gov. Thanks to all members of the Chinese Lateral Node Collaborative Group for their support of this study data and review of this article. The data involved in the article can be shared and contacted by Zhouht1977@163.com.
WX and QL are guarantors of integrity of the entire study. ZSX and QCC were responsible for study concepts and design. ZSX, QCC, BF and YJJ were responsible for literature research. BF, XW, WX, and QL were responsible for experimental studies/data analysis. ZSX and QCC were responsible for manuscript preparation. SCZ edited the manuscript.
This study was supported by the National Key Research and Development Program/Prevent and Control Research for Important Non-Communicable Diseases (No. 2019YFC1315705) and the Medicine and Health Technology Innovation Project of the Chinese Academy of Medical Sciences (No. 2017-12 M-1e006).
The datasets generated and/or analysed during the current study are not publicly available due to the data is confidential patient data but are available from the corresponding author on reasonable request.
The Cancer Hospital of the Chinese Academy of Medical Sciences served as the initiator of the study, and the ethics committee of Cancer Hospital, Chinese Academy of Medical Sciences approved this study (NCC 2017-YZ-026, Oct 17, 2017). Patients provided informed consent and all procedures were performed in agreement with the World Medical Association and the Declaration of Helsinki.
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The authors declare that they have no competing interests.
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By Zhongshi Xie; Qichen Chen; Bo Feng; Yujuan Jiang; Xin Wang; Wei Xing and Qian Liu
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