Recrecimiento tumoral en pacientes bajo esquema de watch-and-wait en cáncer de recto. Ensayo pictórico / Regrowth during watch-and-wait scheme in rectal cancer. Pictorial essay

Resumen En las últimas décadas, la resonancia magnética (RM) ha cobrado un rol fundamental en el diagnóstico, la estadificación y el seguimiento de los pacientes con cáncer de recto. En la estadificación inicial, que sean o no tumores localmente avanzados es lo que determina el tratamiento neoadyuvante o quirúrgico, respectivamente. Posterior a la neoadyuvancia, los pacientes que logren una respuesta clínica completa pueden ser considerados para la inclusión dentro de un esquema de vigilancia activa, comúnmente conocido como watch and wait (WW). La estrategia WW se basa en tres pilares, que son el examen digital rectal, la endoscopía y la RM, buscando detectar la presencia temprana de recrecimiento tumoral. En relación a la RM, la secuencia potenciada en T2 de alta resolución, junto con la de difusión (DWI) y el mapa de ADC, son las piezas clave para la detección temprana de recrecimiento. La estrategia de WW lleva a evitar cirugías resectivas con una alta morbilidad y deterioro de la calidad de vida. El examen digital rectal y la endoscopía son métodos de vigilancia complementarios a la RM, con su principal limitación en lesiones sin compromiso mucoso. Esta razón posiciona a la RM como un pilar indispensable para su implementación, detectando no solo áreas de recrecimiento parietal, sino también aquellas extramurales no accesibles por los otros métodos de vigilancia. En nuestro conocimiento, este es el primer ensayo iconográfico que se centra en el análisis estricto del recrecimiento tumoral en pacientes bajo esquema de WW por RM. El objetivo es enfatizar el protocolo de estudio en estos pacientes y mostrar las distintas formas de recrecimiento tumoral con el fin de lograr su detección temprana.

Abstract During the last decades, the magnetic resonance imaging (MRI) has become an strategic tool for diagnosis, staging and surveillance in patients with rectal cancer. To differentiate patients with locally advanced rectal tumors from those who do not, determinate neoadjuvant therapy or total mesorectal excision, respectively. After neoadjuvant chemoradiotherapy, those who achieve complete clinical response may be considered for inclusion in an active surveillance scheme known as “watch and wait” (WW). WW strategy consists of three pillars, rectal digital exam, endoscopy and the MRI, and the main purpose is to reach the early detection of tumoral regrowth. Regarding MRI, the high-resolution T2-weighted images in conjunction with DWI, and the ADC map plays a key role in this instance. WW leads to avoid resective surgeries with high morbidity rates. The rectal digital exam and endoscopy are complementaries to MRI, whose main limitation is the detection of lesions with no mucosal involvement. This reason places the MRI as a cornerstone in tumoral regrowth, detecting not only luminal regrowth, but those in which the rectal wall is not involved, and thus, not accessible for the other surveillance methods. To our knowledge, this is the first pictorial essay in which imaging regrowth patterns are described. The purpose of this is to emphasize the MRI protocol study and to describe the different forms of tumoral regrowth in order to reach the early tumoral regrowth detection.

Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH) / 中华胃肠外科杂志

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

Evaluation strategy of complete response after neoadjuvant therapy for rectal cancer / 中华外科杂志

Currently, the standard of clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) for local advanced rectal cancer generally lacks pathological examination, the cCR judged by the current standard is still far from the real pathological complete response. After nCRT, due to the presence of tissue edema and fibrosis, MRI is highly uncertain in determining the staging of local lesions. The precision of colonoscopy biopsy is generally low because residual cancer foci exist primarily in the muscular layer, which limits the determination of cCR by colonoscopy biopsy. Local excision through the anus can resect the whole intestinal wall tissue, which is relatively accurate and close to the real state of remission of the lesion, but there are many problems, such as affecting anal function, high rate of complications, and increased difficulty of following radical surgery. Based on the present diagnosis of cCR, the authors put forward the concept of modified cCR (m-cCR) which combined with the pathological standard of transanal multipoint full-layer puncture biopsy (TMFP). It is possible to improve the accuracy of cCR, and improve the safety of cCR patients who receive wait-and-watch therapy without increasing complications or affecting anal function. The exact conclusion needs to be confirmed by further studies.

Immunotherapy for microsatellite-instability-high advanced colorectal cancer / 中华胃肠外科杂志

Microsatellite instability-high (MSI-H) colorectal cancer accounts for approximately 10%-15% of all colorectal cancer patients, while in metastatic diseases the MSI-H population accounts for only 5% of patients. Previous studies have shown that early-stage MSI-H colorectal cancer patients have a good prognosis, but those with advanced disease have a poor prognosis and are not sensitive to chemotherapy. The advent of PD-1 antibodies has significantly improved the prognosis and changed treatment landscape in this population, not only achieving good outcomes in late-line therapy, but also significantly outperforming traditional chemotherapy combined with targeted therapy in first-line therapy. How to overcome primary and secondary drug resistance is a key issue in improving the outcome of MSI-H metastatic colorectal cancer, and commonly used approaches include changing chemotherapy regimens, combining with other immunotherapies, combining with anti-angiogenesis, and local treatments (surgery, radiotherapy, or interventional therapy). It is worth noting that immunotherapy has certain lifelong or even lethal toxicity, and the indications for neoadjuvant immunotherapy must be evaluated with caution. Neoadjuvant immunotherapy in MSI-H advantaged population can achieve high rates of pathological complete remission (pCR) and clinical complete remission (cCR). Therefore, for MSI-H patients with a strong intention to preserve anal sphincter and a strict evaluation of cCR after neoadjuvant immunotherapy, the Watch-and-Wait strategy offers an opportunity to preserve sphincter function and improve long-term survival quality in a subset of mid-to-low rectal cancers. Research on adjuvant immunotherapy in the field of colorectal cancer is also in full swing, and the results are worth waiting for.

Long-term outcomes of watch&wait (W&W) after neoadjuvant treatment in patients with rectal cancer / 中华放射肿瘤学杂志

Objective:To compare the outcomes of watch&wait (W&W) strategy in patients with locally advanced rectal cancer who achieved complete clinical response (cCR) after neoadjuvant therapy, with those who obtained pathological complete response (pCR) after total mesorectal excision (TME).Methods:This is a retrospective cohort analysis study. Patients histologically proven with locally advanced rectal adenocarcinoma (stage Ⅱ-Ⅲ) who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing neoadjuvant therapy and follow-up ≥1 year (W&W group), and patients who did not have cCR but pCR after TME (pCR group). The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (NR-DFS), and organ preservation rate. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM).Results:A total of 118 patients were enrolled, 49 of whom had cCR and managed by W&W, 69 had pCR, with a median follow-up period of 49.5 months (12.1-79.9 months). No difference was observed in the 3-year OS (97.1% vs. 96.7%) and 5-year OS (93.8% vs. 90.9%, P=0.696) between the W&W and pCR groups. Patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs. 43.5%, P<0.001), better 3-year DFS (83.6% vs. 97.0%) and 5-year DFS (83.6% vs. 91.2%, P=0.047) compared with those achieving pCR. The 3-year NR-DFS (95.9% vs. 97.0%) and 5-year NR-DFS (92.8% vs. 97.0%, P=0.407) did not significantly differ between the W&W and pCR groups. Local regeneration occurred in six cases, and 87.7% of patients had successful rectum preservation in the W&W group. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs. 26.5%, P<0.001) was noted in the W&W group. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19.0 vs. 9.8 weeks, P<0.001). Conclusions:The oncological outcomes of W&W strategy in patients with locally advanced rectal cancer are safe and effective, significantly improving the quality of life. Longer interval for cCR evaluation may improve rectal organ preservation rate.

Advances in Neoadjuvant Therapy for Locally Advanced Rectal Cancer / 肿瘤防治研究

The treatment of locally advanced rectal cancer (LARC) is extremely challenging, and it is difficult to achieve satisfactory results with surgical resection alone. In recent years, the diagnosis and treatment of LARC tends to be multi-disciplinary (MDT) mode. The emerging neoadjuvant treatment strategy is a milestone. At present, the preferred treatment for LARC is neoadjuvant chemoradiotherapy combined with total mesorectal excision. This article summarizes the main treatments of LARC neoadjuvant therapy, hoping to provide reference for clinical diagnosis and treatment.

Prognostic factors from squamous cell carcinoma of the hard palate, gingiva and upper alveolar ridge

Abstract: The purpose of this study was to evaluate the clinicodemographic characteristics and treatment protocol as prognostic factors in patients with oral squamous cell carcinoma (OSCC) of the hard palate, upper gingiva, and alveolar ridge (HPUGAR). This retrospective cohort study collected data of patients treated in two head and neck surgery departments in southern Brazil between 1999 and 2021. Information on clinicodemographic data, habits, site, size, clinical aspect, clinical staging, cervical metastasis, treatment, and survival was collected. Associations between independent variables and outcomes were assessed using Pearson's chi-square test and binary regression. Kaplan-Meier test was employed to compare the survival between the neck approaches. Forty-one patients were included; most were male (61%), with a mean age of 68.8 (± 13.9) years. The consumption of tobacco (p = 0.003) and alcohol (p = 0.02) was significantly higher in male than in female patients. The main clinical features observed in the study sample were lesions larger than 2 cm (48.7%), no cervical (90.2%), or distant metastasis (90.2%). Surgery alone was the main treatment approach (48.8%). The watch-and-wait strategy was adopted in 34 cases (83.0%), while elective neck dissection was applied in five (12.2%). Only two patients with cN0 disease (4.9%) presented with cervical metastasis at follow-up. Eight patients (12.2%) died of the disease. Clinicodemographic variables, habits, surgical margins, and histological subtype were not significantly associated with cervical metastasis or survival. Cervical metastasis (p = 0.004) was associated with poor survival. No difference was detected in survival between different neck approaches (p = 0.28). Cervical metastasis and local recurrence are negative prognostic factors for HPUGAR OSCC.

Feasibility of wait and watch strategy for patients with high-risk factors after endoscopic submucosal dissection for early colorectal cancer / 国际外科学杂志

Objective:To explore the feasibility of wait and watch treatment for patients with high-risk pathology factors after endoscopic submucosal dissection (ESD) for early colorectal cancer.Methods:From December 2012 to June 2020, 104 patients, including 62 males and 42 females, aged from 31 to 89 years old, with the average of (59.5±10.8) years with early colorectal cancer after ESD operation were selected from the Department of General Surgery, Beijing Friendship Hospital, Capital Medical University. According to the follow-up treatment, the patients were divided into two groups: the additional surgical resection group and the wait and watch group. The measurement data of normal distribution were shown by mean standard deviation, the comparison between groups adopted t test, and the comparison of counting data between groups adopted χ2 test. The types of pathological high-risk factors after ESD were compared between the two groups, and the overall survival (OS) and progression free survival (PFS) of the two groups were compared by Log-Rank test. Results:The median follow-up time was(40.6±15.3) months. The OS and PFS of the additional surgical resection group and the wait and watch group were 100.0% vs 98.4% and 90.7% vs 90.2%, respectively, and there was no statistically significant difference between the two groups (OS: χ2=0.875, P=0.35; PFS: χ2=0.017, P=0.80). Conclusion:The wait and watch strategy is expected to be one of the follow-up choices for some patients with high risk factors after ESD operation for early colorectal cancer.

Current situation and think of watch and wait strategy after neoadjuvant treatment of rectal cancer / 国际外科学杂志

Some patients with rectal cancer can achieve clinical complete response (cCR) after neoadjuvant chemoradiotherapy. The watch and wait strategy for cCR patients can achieve similar curative effects as radical surgery, avoid surgical complications, and significantly improve the quality of life of patients, which is attracting increasing attention. Although the existing research results support that the watch and wait strategy is safe and feasible, there is still a lack of high-level evidence-based medicine evidence. There are still many issues in the implementation of the watch and wait strategy that need to be further clarified, including long-term oncology efficacy, cCR diagnosis and evaluation criteria, appropriate patient selection, follow-up strategies during the observation period, and treatment methods for local tumor regeneration. This article will explain the above problems based on the results of the existing literature and the clinical experience of our center.

Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors / 中华胃肠外科杂志

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.

Interpretation of the 2020 American society of colon and rectal surgeons clinical practice guidelines for the management of rectal cancer / 中华胃肠外科杂志

Located in the pelvic cavity and contiguous to the anal sphincter complex and urogenital organs, the rectum has more intricate anatomical features compared with the colon. Consequently, the treatment of rectal cancer involves more consideration, including pelvic radiation, lateral lymph node dissection, transanal access, postoperative function, sphincter preservation, and nonoperative management. Based on the last set of American society of colon and rectal surgeons (ASCRS) practice parameters for the management of rectal cancer published in 2013, the 2020 guidelines present evidence-based updates for both long-existing and emerging controversies on surgical management of rectal cancer. These updates include the indication for local resection, lymph node dissection for radical proctectomy, minimally invasive surgery, the "watch and wait" strategy for patients with clinical complete response, and prevention of anastomotic leak. Meanwhile, the guidelines recommend a risk-stratified approach for perioperative therapies for non-metastatic disease, and an individualized multimodality treatment based on treatment intent for synchronous metastatic disease.

Looking back 2019: focusing on the development and research of colorectal surgery in China / 中华胃肠外科杂志

Although the surgical treatment of colorectal disease progresses slowly, with the advancement of minimally invasive surgical techniques, perioperative comprehensive treatment strategies and clinical research in recent years, Chinese colorectal surgery has developed rapidly. Transanal total mesorectal excision, lateral pelvic lymph node dissection,"watch and wait"strategy for clinical complete response of neoadjuvant radiotherapy for rectal cancer, and robotic colorectal surgery are still hot topics in colorectal surgery in recent years. The construction of clinical registry database and clinical research for colorectal cancer surgery are discussed, with a view to combing the development of colorectal surgery for colleagues in the surgical field, and to seek the development of colorectal surgery in China.

Diagnosis and Treatment of Rosai-Dorfman Disease of the Spine / 中华骨科杂志

Objective:to review the clinical features, diagnosis and treatment of spinal Rosai-Dorfman disease(RDD).Methods:we conducted a systemic review and collected the cases reported from 2010. The key words were Rosai-Dorfman disease, spine/central nervous system. We screened both English and Chinese database. There were 43 reports finally included in the study, containing 52 cases. We distracted the information of interest and, subsequently, analyzed the harvested data using specific statistical software packages. The study focused on the summary and description of the clinical features, diagnosis and treatment and prognosis of spinal RDD.Results:The included articles reported 52 cases. The average age was 32.1±17.1 years (ranging from 6 to 76 years old). The ratio of male to female was 1.9/1. The median follow-up period was 19.9 months. The initial symptoms of 41 patients (78.8%) were spinal lesion-related. The cases with painless lymph nodes enlargement, other organ lesions and abnormal lab tests were 11.5%, 36.5% and 23.1%, respectively. The frequent infringed segments were cervical (43.1%) and thoracic (39.2%) spine. 53.2% lesions were dura-based, while 17.0% and 10.6% for bone and cord, respectively. Surgery was the mainstream of the treatment armamentarium, composing 83.7% cases, among which 46.3% underwent total resection. Cases only treated with radiotherapy, chemotherapy and steroids were 10.2%. Very Few cases remitted spontaneously (2.0%). The risk of recurrence and occurrence at other vertebral levels was 22.0%.Conclusion:It is rare for spinal involvement of RDD. This entity has no pathognomonic clinical and imaging features. RDD has a tendency of multi-organ involvement and recurrence. Surgery remains the mainstay of the treatment, but the efficacy of other adjuvant therapies is not sure. A wait and watch strategy is employed for asymptomatic patients.

Precise preoperative staging of low rectal cancer assessed by imaging / 中国实用外科杂志

The goal of treatment strategy for patients who has low rectal cancer is preserving sphincter and function and keeping decrease of local recurrence and increase overall survival. In the result of narrow space between tumor and surrounding structure,the positive resection margin increases the local recurrence in patient with low rectal cancer. Magnetic resonance imaging(MRI)preoperatively predict circumferential resection margin according to the relationship between tumor and the low rectal cancer surgical resection plane. MRI,which has been validated by previous studies,low rectal plane assessment,reducing pCRM involvement and avoiding overtreatment through selective preoperative therapy and rationalized use of permanent colostomy. However,surgical treatment of low rectal cancer is controversial,and one of the reasons is the lack of definition and standardization of surgery in low rectal cancer. Classification of low rectal cancers and standardization of surgery according to distance between lowest edge of tumor and depth of tumor invasion permit sphincter and function preserving surgery in of patients with low rectal cancer. In patients with rectal cancer who achieve clinical complete response after neoadjuvant chemoradiotherapy,“watch and wait” is a novel management strategy with potential to avoid major surgery. However,how to select proper candidates and how to assess the complete clinical response need further research.

Several issues worthy of attention in clinical research of low rectal cancer / 中国实用外科杂志

Total mesorectal excision(TME) regulates the extent of resection of low rectal cancer surgery and is the gold standard for low rectal cancer. Colorectal surgeons need to comprehensively consider the comprehensive treatment strategy for rectal cancer to reduce the risk of local recurrence,how to protect patients' anal,sexual and urinary function,and improve their quality of life,and consider how to reduce surgical trauma. At present,the research hotspots in the fieldof rectal cancer diagnosis and treatment turn to how to betterprotect the function and further reduce the risk of localrecurrence. Among them,the "watch and wait" strategy of "clinical complete response" after neoadjuvant chemoradiotherapy,the lateral lymph node dissection and the procedure of transanal total mesorectal excision,is a hot issue in clinical research.

Application value of colonoscopic assessment in "watch and wait" strategy for mid-lower rectal cancer after neoadjuvant chemoradiotherapy / 中华胃肠外科杂志

Objective@#To investigate the value of colonoscopic assessment in "watch and wait" strategy for mid-lower rectal cancer after neoadjuvant chemoradiotherapy (nCRT).@*Methods@#A single-center retrospective case series study was performed. Database of mid-lower rectal cancer patients at Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute from March 2011 to June 2017 was retrieved. Inclusion criteria: (1) nCRT was completed (50.6 Gy/22 f, plus oral capecitabine); (2) radical surgery was performed within 12 weeks after nCRT treatment; (3) clinical response to nCRT was determined as clinical complete response (cCR) or near-cCR. Patients who did not undergo colonoscopy and MRI in our center during initial assessment and follow-up, or whose colonoscopy data were unable to re-evaluated, were excluded. Initial evaluation of nCRT response was carried out between 6 and 16 weeks after nCRT. The results of endoscopy (eCR, near-eCR and non-eCR) and MRI (mCR, near-mCR and non-mCR) were compared to local lesion relapse during follow-up. The consistency of the results of colonoscopy and MRI was evaluated by Kappa test (Kappa value of 0.21 to 0.40 indicates general consistency, 0.41 to 0.60 moderate consistency, and 0.61 to 0.80 high consistency). The non-regrowth disease-free survival (NR-DFS) curves of the eCR group and the near-eCR group were plotted by Kaplan-Meier method and compared by log-rank test. Clinical significance of colonoscopy examination in the following "watch and wait" strategy during follow-up period was analyzed.@*Results@#A total of 32 patients were enrolled in the study, including 21 (65.6%) males and 11 (34.4%) females with a median age of 57 years old. The differentiated type of rectal cancer included 1 (3.1%) case of well-differentiated, 26 (81.2%) of moderately differentiated and 5 (15.6%) of poorly differentiated. Clinical stage of the patients included 9 (28.1%) cases of T2-3N0 and 23 (71.9%) of T2-3N+. Median follow-up period was 48 (18 to 80) months. The local regrowth rate was 34.4% (11/32) and median interval of local regrowth was 10.0 (4 to 37) months. Initial colonoscopy evaluation was carried out at a median time of 9 (5 to 19) weeks after nCRT was completed. According to endoscopic findings, patients were divided into 3 groups, including 15 cases in eCR group, 15 cases in near-eCR group and 2 cases in non-eCR group. According to the appearance of MRI, patients were divided into 3 groups, including 8 cases in mCR group, 21 cases in near-mCR group and 3 cases in non-mCR group. The regrowth rate of eCR group was lower than that of mCR group (1/15 vs. 1/8) without significant difference (P=1.000). The regrowth rate of near-eCR group was higher than that of near-mCR group [9/15 vs. 42.9% (9/21)] without significant difference as well (P=0.500). The consistency between colonoscopy and MRI in response evaluation of cCR or near-cCR after nCRT was unsatisfactory (Kappa=0.341, P=0.011). After initial evaluation, 31 patients underwent watch and wait strategy, and 1 underwent local resection. The 1- and 3-year NR-DFS in the eCR group was both 100%, which was higher than that in the near-eCR group (53.3% and 38.9%, respectively), and the difference was statistically significant (P=0.001). During watch and wait period, 11 cases developed local regrowth by colonoscopy examination and the biopsy result included 4 case of high-grade intraepithelial neoplasia (HIN), 6 cases of adenocarcinoma and 1 case of chronic mucosal inflammation. Meanwhile lateral developmental tumor of ascending colon in 1 case and of sigmoid in a case was found by colonoscopy and confirmed as HIN by postoperative pathology. Besides, 4 cases developed colonic multiple adenoma and all underwent endoscopic resection.@*Conclusion@#Colonoscopy examination plays an important role in both initial assessment and regrowth monitoring during watch and wait strategy after nCRT treatment.

"Watch and wait" strategy after neoadjuvant therapy for rectal cancer: status survey of perceptions, attitudes and treatment selection in Chinese surgeons / 中华胃肠外科杂志

Objective@#To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT).@*Methods@#A cross-sectional survey was used in this study. Selection of subjects: (1) Domestic public grade III A (provincial and prefecture-level) oncology hospitals or general hospitals possessing the radiotherapy department and the diagnosis and treatment qualifications for colorectal cancer. (2) Surgeons of deputy chief physician or above. Using the "Questionnaire Star" online survey platform to create a questionnaire about cognition, attitude and treatment choice of the "watch and wait" strategy after cCR following nCRT for rectal cancer. The questionnaire contained 32 questions, such as the basic information of doctor, the current status of rectal cancer surgery, the management of pathological complete remission (ypCR) after nCRT for rectal cancer, the selection of examination items for diagnosis of cCR, the selection of suitable people undergoing "watch and wait" approach, the nCRT mode for promotion of cCR, the choice of evaluation time point, the willingness to perform "watch and wait" approach and the treatment choice, and the risk and monitoring of "watch and wait" approach. A total of 116 questionnaires were sent to the respondents via WeChat between January 31 and February 19, 2019. Statistical analysis was performed using Fisher′s exact test for categorical variables.@*Results@#Forty-eight hospitals including 116 surgeons meeting criteria were enrolled, of whom 77 surgeons filled the questionnaire with a response rate of 66.4%. "Watch and wait" strategy was carried out in 76.6% (59/77) of surgeons. Seventy surgeons (90.9%) were aware of the ypCR rate of rectal cancer after preoperative nCRT and 49 surgeons (63.6%) knew the 3-year disease-free survival of patients with ypCR in their own hospitals. Fifty-five surgeons (71.4%) believed that patients with ypCR undergoing radical surgery met the treatment criteria and were not over-treated. Three most necessary examinations in diagnosing cCR were colonoscopy (96.1%, 74/77), digital rectal examination (DRE) (90.9%,70/77) and DWI-MRI (83.1%, 64/77). Responders preferred to consider a "watch and wait" strategy for patients with baseline characteristics as mrN0 (77.9%, 60/77), mrT2 (68.8%, 53/77) and well-differentiated adenocarcinoma (68.8%, 53/77). Sixty-six surgeons (85.7%) believed that long-term chemoradiotherapy (LCRT) with combination or without combination of induction and/or consolidation of the CapeOX regimen (capecitabine + oxaliplatin) should be the first choice as a neoadjuvant therapy to achieve cCR. Forty-one surgeons (53.2%) believed that a reasonable interval of judging cCR after nCRT should be ≥ 8 weeks. Forty-four surgeons (57.1%) routinely, or in most cases, informed patient the possibility of cCR and proposed to "watch and wait" strategy in the initial diagnosis of patients with non-metastatic rectal cancer. Thirteen surgeons (16.9%) would take the "watch and wait" strategy as the first choice after the patient having cCR. Fifty-two surgeons (67.5%) would be affected by the surgical method, that was to say, "watch and wait" approach would only be recommended to those patients who would achieve cCR and could not preserve the anus or underwent difficult anus-preservation surgery. Sixteen surgeons (20.8%) demonstrated that "watch and wait" strategy would not be recommended to patients with cCR regardless of whether the surgical procedure involved anal sphincter. Eleven surgeons (14.3%) believed that the main risk of "watch and wait" approach came from distant metastasis rather than local recurrence or regrowth. Twenty-nine of surgeons (37.7%) did not understand the difference between "local recurrence" and "local regrowth" during the period of "watch and wait". Twenty-six surgeons (33.8%) thought that the monitoring interval for the first 3 years of "watch and wait" strategy was 3 months, and the follow-up monitoring interval could be 6 months to 5 years. Surgeons from cancer specialist hospitals had higher approval rate, notification rate, and referral rate of "watch and wait" strategy than those from general hospitals. Thirty-one surgeons (42.5%) considered that the difficulty and concern of carrying out "watch and wait" approach in the future was the disease progress leading to medical disputes. Twenty-six surgeons (35.6%) demonstrated that their concern was lack of uniform evaluation standard for cCR.@*Conclusions@#Chinese surgeons seem to have inadequate knowledge of non-operative management for rectal cancer patients achieving cCR after nCRT and show relatively conservative attitudes toward the strategy. Chinese consensus needs to be formed to guide the non-operative management in selected patients. Chinese Watch & Wait Database (CWWD) is also needed to establish and provide more evidence for the use of alternative procedure after a cCR following nCRT.

Advances of optimized neoadjuvant therapy in the treatment of locally advanced rectal cancer / 中华胃肠外科杂志

Neoadjuvant chemoradiotherapy is the current standard of care for locally advanced rectal cancer. However, this modality is facing more and more challenges. The research progress on this issue around the world can be summarized into three aspects. The first is to increase the intensity of treatment to obtain better tumor regression, such as adding a second drug during the neoadjuvant chemoradiotherapy, prolonging the interval and receiving sufficient chemotherapy before surgery. Current research data are not sufficient to support strategies for adding drugs or receiving sufficient chemotherapy before surgery, but it may be worth looking forward to adding irinotecan during neoadjuvant chemoradiotherapy, and an appropriate extension of the interval before surgery may also be a good option. Secondly, we can reduce the intensity of treatment to improve the quality of life of patients with a non-inferior clinical outcome, such as non-surgical approach, local excision rather than total mesorectal excision and removal of preoperative radiotherapy. The data of the International Watch & Wait Database (IWWD) suggest that patients with a Watch & Wait strategy have similar long-term survival outcomes as those who have undergone surgery and have pathologic complete response, meanwhile the data are still inadequate to support using local excision instead of total mesorectal excision, or removal of preoperative radiotherapy strategies. Finally, to achieve a precise individual treatment, some potential biomarkers are investigated via genomics, metabolomics and radiomics. But so far, there is no recognized biomarker for clinical treatment in the field of neoadjuvant therapy for rectal cancer. This article summarizes the clinical research progress of locally advanced rectal cancer in recent years from the above three aspects.

Current status and perspectives on "watch and wait" strategy for rectal cancer patients after clinical complete response following neoadjuvant chemoradiation / 中华胃肠外科杂志

Neoadjuvant chemoradiation has been accepted as a standard of care for local advanced middle to low rectal cancer. Patients with clinical complete response (cCR) or near cCR following neoadjuvant chemoradiation may benefit from watch and wait strategy or organ-preserving surgery with good short- and long-term outcome and quality of life (QOL). Yet the criteria of cCR varies and cCR is not consistent with pCR. Therefore, the obstacle to the strategy lies on whether its failure can be salvaged and the complexity of follow-up. Available studies demonstrated that local recurrence or regrowth can be salvaged by surgery without compromising the survival. So, the key is appropriate follow-up schedule and timely salvage. The strategy has not drawn much attention until recently, and relevant studies go slowly because of low data availability, patient awareness, and peer acceptance. We still believe that more and more patients might benefit from this strategy, along with the increasing attention of QOL from the patients. That may be obtained through screening of the right patients and optimizing treatment modality, evaluation methods, and protocol of follow-up.

Transition of treatment strategy for locally advanced rectal cancer towards "watch and wait" / 中华胃肠外科杂志

Therapeutic goal for locally advance rectal cancer (LARC) patients includes long-term survival and function preservation of pelvic organs. During the recent two decades, treatment strategy for LARC is gradually shifing to minimally invasive surgery, even avoiding a major surgery. "Watch and wait (W&W)" strategy is effective in dramatically decreasing surgical trauma and significantly improving preservation of defecation, urination and sexual function. Total neoadjuvant therapy (TNT) shifts all or part of adjuvant chemotherapy to the neoadjuvant phase and has showed obvious advantage in tumor shrinkage and complete clinical response (cCR) achievement. This article will summarize the transition of treatment strategy of LARC towards W&W from standard treatment. After more than ten years of development, both NCCN and ESMO guidelines recommend stratified neoadjuvant treatment considerations based on distinct risk classifications and especially suggest TNT for LARC patients with advanced diseases, which affirms the value of TNT in tumor shrinkage. Although accumulating data show that pelvic control and organ preservation using W&W strategy after cCR is equal or non-inferior to standard surgery, impact on long-term survival still needs prospective randomized controlled study; no consensus has been achieved for the detail of the W&W strategy. Thus W&W strategy is suggested to applied in hospitals specialized in the treatment of rectal cancer within the framework of multiple disciplinary treatment. In view of special medical conditions of our country, we still need to accumulate more experience and data of W&W strategy for rectal cancer patients with appeals for sphincter preservation and actively participate in international researches.