Patients and study design
A retrospective study was performed based on the constructed database at Peking Union Medical College Hospital (PUMCH), Department of General Surgery. TEM has been adopted for treating early rectal cancer for one decade in PUMCH. Surgeons in our unit have accumulated abundant clinical experience, and patients’ intact pathological and clinical information were available in the specific database created in our clinical center.
The present study involved patients who underwent TEM in our clinical center and were diagnosed with intermediate risk early rectal cancer via pathological examination, in accordance with relevant guidelines, between January 2010 and December 2017. Intermediate risk early rectal cancer was defined as a patient with one of the following properties: (1) pT1: Diameter range from 3 to 5 cm or < 3 cm but accompanied with at least one risk factor, including lymphatic and/or venous invasion and/or neural invasion and/or poor differentiation; or (2) pT2: Diameter less than 3 cm with the absence of any risk factors. For large benign lesions with small invasive component, tumor size was considered to be the maximum diameter of malignant tissue during pathological examination. Before the TEM procedure, all patients underwent pelvic MRI to exclude nodal metastases and preoperative colonoscopy to obtain biopsy results to satisfy the indications for surgery. Patients who met the following criteria were excluded from the study: (1) unable to give consent due to dementia; (2) barrier in comprehension of the questionnaire provided; (3) failed to return questionnaires by the cutoff date; and (4) diagnosed with malignant rectal neoplasms other than adenocarcinomas. All patients in our clinical center diagnosed with intermediate risk pT1 or pT2 rectal cancer were recommended to receive the following treatment, including adjuvant CRT or radical surgery. Patients bearing intermediate risk rectal cancer who underwent adjuvant therapy after TEM were in a follow-up that included more intense postoperative examinations.
Patients meeting the selection criteria were grouped into the TME group (including LAR and APR) or adjuvant treatment group. Oncological outcome was acquired from telephone interviews and outpatient follow-up records. Functional outcome was primarily obtained from distributed paper questionnaires, online fillings and telephone follow-up. The European Organization for Research and Treatment of Cancer Quality of Life colorectal cancer specific module (EORTC-QLQ-CR29) was used to obtain an overall impression of a patient’s HRQoL. Low anterior resection syndrome (LARS) score and Wexner score were used as scales to assess patients’ defecatory or anorectal function. The Female Sexual Function Index (FSFI) and five items version of the International Index of Erectile Function (IIEF-5) were used to evaluate female and male postoperative sexual function, respectively. To avoid bias from potential confounding variables, we used the Propensity Score match (PSM) method (match tolerance = 0.05). Enrolled patients had an average 42.63 months of follow-up (range 12 – 73 months).
Specimens resected during TEM were reviewed by experienced pathologists and diagnosed as intermediate risk pT1 or pT2 rectal cancer. Patients underwent radical surgeries 4 - 8 weeks after primary TEM. The choice of surgical technique between LAR and APR were primarily determined by the distance from the anal verge. All patients were informed of the possibility and inconvenience created by a permanent stoma. The anastomosis method involved stapling and hand sewing. Surgeons assessed the suitable time for diverse stoma if it was suitable. Patients received a contrast enema and abdominal CT scan before the reversal to certify the continuity and liquidity of the distal digestive tract and exclude probable distant metastasis. Patients who had lymph node metastasis on pathological examination after TME were recommended for subsequent adjuvant therapy.
Postoperative CRT included concurrent chemoradiotherapy (CCRT) and radiotherapy alone. Patients who received CCRT had a long course of radiotherapy with the chemotherapeutics. Chemotherapy regimen primarily included single-agent capecitabine, oxaliplatin plus intravenous 5-Fu/LV (FOLFOX) or oxaliplatin combined with capecitabine (XELOX). The choice of regimen was determined based on the oncologist’s judgment.
Patients’ oncological prognoses were assessed using overall survival (OS) and disease-free survival (DFS). The interval of OS was the time between the primary surgery and the date of death. The DFS interval was calculated as the interval between the primary surgery and recurrence date. Recurrence was primarily confirmed via biopsy during follow-up colonoscopy, and death information was certified via telephone interviews.
The following questionnaires were distributed after radical surgery or the eventual course of adjuvant treatment. For patients who received LAR with diverting ileostomy, the questionnaires were distributed after the reversal of stoma. For patients who underwent APR or LAR without diverting ileostomy, the questionnaires were sent after primary radical surgeries. Since patients in the adjuvant therapy group did not have stoma, the items related to stoma care was not listed in the distributed modules.
EORTC QLQ-CR29 is a specific module of conventional EORTC QLQ-C30 for colorectal cancer patients, and it consists roughly of 4 main scales and 18 diverse single items . All items are divided into functioning scales and symptom scales. Answers were graded as the extent of severity from 1 (not at all) to 4 (very much) and from 1 (very poor) to 7 (excellent) for items about HRQoL. The initially calculated scores were transformed into scales of 0 – 100 according to a previously reported standard procedure .
LARS score and Wexner score
These two scales were used primarily to evaluate defecation problems. The LARS score has 5 questions on bowel movement-related disability, such as control of ﬂatus, feces and liquid stool. The total LARS score ranges from 0 to 42. Patient scores of 0 to 20, 21 to 29 and 30 to 42 were categorized as no LARS, minor LARS and major LARS, respectively . The Wexner score includes 5 questions on the frequency of solid and liquid stool, gas incontinence and the frequency of using a pad due to fecal incontinence. The overall Wexner score ranged from 0 to 20, and a higher score indicates greater severity of fecal incontinence .
FSFI and IIEF-5
HRQoL problems related to sexual dysfunction were evaluated using the FSFI for female patients and the IIEF-5 for male patients. FSFI is a self-report scale that includes 6 domains (desire, arousal, lubrication, orgasm, satisfaction and pain). The separate scores for each domain are calculated as a total score . IIEF-5 consists of 5 questions about male erectile function. The severity of erectile dysfunction (ED) was categorized as severe (5 to 7), moderate (8 to 11), mild to moderate (12 to 16), mild (17 to 21) and no dysfunction .
Continuous variables are presented as the means (range) or proportions as necessary. Differences in continuous variables, such as median LARS score, were examined using the Mann-Whitney U test. Categorical variables in this study were assessed using Pearson’s chi-squared test or Fisher’s exact test (if applicable). Criteria for significant differences was a p value < 0.050. A p value < 0.001 was defined as an extremely distinct difference. The Kaplan-Meier method was used to compare OS and DFS. The log-rank test was used to distinguish differences in oncological outcome. Statistical analyses were performed using SPSS version 24.0 for Windows (SPSS Inc., Chicago, IL, USA).