Oncologic Outcomes of Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma Initially Managed with Chemoradiation.

Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan-Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11-47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5-66.5%), 54.5% (95% CI 44.4-66.8%), and 26.8% (95% CI 18.6-38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16-46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99-42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05-6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.

Is Nonoperative Management of Rectal Cancer Feasible?

During the past decade, the treatment of locally advanced rectal cancer (LARC) has become more complex. Total neoadjuvant treatment (TNT) has increased the rates of both clinical and pathologic complete response, resulting in improved long-term oncological outcomes. The feasibility to implement nonoperative management (NOM) depends on solving current challenges such as how to correctly identify the best candidates for a NOM without compromising oncologic safety. NOM should be part of the treatment discussion of LARC, considering increasing rates of clinical complete response, potential quality of life gains, avoidance of surgical morbidity, and patient preferences.

Non-Operative Management of Patients with Rectal Cancer: Lessons Learnt from the OPRA Trial.

Over the past decade, the management of locally advanced rectal cancer (LARC) has progressively become more complex. The introduction of total neoadjuvant treatment (TNT) has increased the rates of both clinical and pathological complete response, resulting in excellent long-term oncological outcomes. As a result, non-operative management (NOM) of LARC patients with a clinical complete response (cCR) after neoadjuvant therapy has gained acceptance as a potential treatment option in selected cases. NOM is based on replacement of surgical resection with safe and active surveillance. However, the identification of appropriate candidates for a NOM strategy without compromising oncologic safety is currently challenging due to the lack of an objective standardization. NOM should be part of the treatment plan discussion with LARC patients, considering the increasing rates of cCR, patient preference, quality of life, expectations, and the potential avoidance of surgical morbidity. The recently published OPRA trial showed that organ preservation is achievable in half of rectal cancer patients treated with TNT, and that chemoradiotherapy followed by consolidation chemotherapy may an appropriate strategy to maximize cCR rates. Ongoing trials are investigating optimal algorithms of TNT delivery to further expand the pool of patients who may benefit from NOM of LARC.

Nonoperative Management for Rectal Cancer.

The treatment algorithm for locally advanced rectal cancer (LARC) has increased in complexity over the past 10 years. Nonoperative management (NOM) for rectal cancer in patients with clinical complete response (cCR) after neoadjuvant therapy has been gaining acceptance as a potential treatment option for selected LARC patients. The current challenge is to accurately select the patients with an apparent cCR, thereby correctly identifying those would-be appropriate candidates for a NOM strategy. NOM should be part of the treatment discussion of LARC, considering increasing rates of cCR, patient preference, potential quality of life gains, and the potential avoidance of surgical morbidity.

Neoadjuvant Therapy for Rectal Cancer.

The treatment of locally advanced rectal cancer is challenging and requires a multidisciplinary approach. Neoadjuvant treatment has improved local control by the combination of radiotherapy, surgery, and chemotherapy. However, neoadjuvant treatment has not yet been shown to improve overall survival and is associated with toxicities and late sequelae that impair the quality of life of patients. Currently, different types of neoadjuvant strategies have raised the question about which one is the optimal strategy for rectal cancer treatment. In this article, we explore the different neoadjuvant treatment regimens currently available, their associated benefits and toxicities, and novel approaches in this area.

Options for Low Rectal Cancer: Robotic Total Mesorectal Excision.

Low rectal cancers (LRCs) may offer a difficult technical challenge even to experienced colorectal surgeons. Although laparoscopic surgery offers a superior exposure of the pelvis when compared with open approach, its role in rectal cancer surgery has been controversial. Robotic platforms are well suited for difficult pelvic surgery due to its three-dimensional visualization, degree of articulation of instruments, precise movements, and better ergonomics. The robot may be suitable especially in the anatomically narrow pelvis such as in male and obese patients. Meticulous dissection in critical steps, such as splenic flexure takedown, nerve-sparing mesorectal excision, and distal margin clearance, are potential technical advantages. In addition, robotic rectal resections are associated with lower conversion rates to open surgery, less blood loss, and shorter learning curve with similar short-term quality of life outcomes, similar rates of postoperative complications, and equivalent short-term surrogate outcomes compared with conventional laparoscopy. Robotic surgery approach, if used correctly, can enhance the skills and the capabilities of the well-trained surgeon during minimally invasive procedures for LRC.

Malakoplakia mimicking a locally advanced colorectal neoplasm.

Malakoplakia is a rare disease. Clinical presentation is non-specific, making its diagnosis an incidental finding on histopathological analysis. The aim of this case report is to describe a patient diagnosed with colon, renal and soft tissue malacoplakia mimicking a locally advanced colorectal cancer. A 75-year-old man was admitted due to intense abdominal pain. No relevant findings at the physical examination. Computed tomography showed parietal thickening of the descending colon with left kidney, iliopsoas muscle and retroperitoneum involvement. An elevated blood serum creatinine, elevated glycated hemoglobin and urinary infection were detected. Surgery was decided for suspicious symptomatic colonic neoplasm. Left segmental colectomy with left partial nephrectomy and retroperitoneal soft tissue resection was performed. Pathology report was compatible with malakoplakia. Malakoplakia is a rare disease and may affect multiple organs. Because there are no clinical-specific findings, diagnosis is usually made with histopathological study of the surgical specimen.

Comparative analysis of the Memorial Sloan Kettering Bowel Function Instrument and the Low Anterior Resection Syndrome Questionnaire for assessment of bowel dysfunction in rectal cancer patients after low anterior resection.

AIM: Neoadjuvant therapy and total mesorectal excision (TME) for rectal cancer are associated with bowel dysfunction symptoms known as low anterior resection syndrome (LARS). Our study compared the only two validated instruments-the LARS Questionnaire (LARS-Q) and the Memorial Sloan Kettering Bowel Function Instrument (MSK-BFI)-in rectal cancer patients undergoing sphincter-preserving TME. METHODS: One hundred and ninety patients undergoing sphincter-preserving TME for Stage I-III rectal cancer completed the MSK-BFI and LARS-Q simultaneously at a median time of 12 (range 1-43) months after restoration of bowel continuity. Associations between the MSK-BFI total/subscale scores and the LARS-Q score were investigated using Spearman rank correlation (r s ). Discriminant validity for the two questionnaires was assessed, and the questionnaires were compared with the European Quality of Life Instrument. RESULTS: Major LARS was identified in 62% of patients. The median MSK-BFI scores for no LARS, minor LARS and major LARS were 76.5, 70 and 57, respectively. We found a strong association between MSK-BFI and LARS-Q (r s -0.79). The urgency/soilage subscale (r s -0.7) and the frequency subscale (rs -0.68) of MSK-BFI strongly correlated with LARS-Q. Low correlation was observed between the MSK-BFI diet subscale and LARS-Q (r s -0.39). On multivariate analysis, both questionnaires showed worse bowel function in patients with distal tumours. A low to moderate correlation with the European Quality of Life Instrument was observed for both questionnaires. CONCLUSIONS: The MSK-BFI and LARS-Q showed good correlation and similar discriminant validity. As the LARS-Q is easier to complete, it may be considered the preferred tool to screen for bowel dysfunction.

Patient-Reported Bowel Function in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy After Neoadjuvant Therapy: A Case-Control Study.

BACKGROUND: A watch-and-wait strategy is a nonoperative alternative to sphincter-preserving surgery for patients with locally advanced rectal cancer who achieve a clinical complete response after neoadjuvant therapy. There are limited data about bowel function for patients undergoing this organ-preservation approach. OBJECTIVE: The purpose of this study was to compare bowel function in patients with rectal cancer managed with a watch-and-wait approach with bowel function in patients who underwent sphincter-preserving surgery (total mesorectal excision). DESIGN: This was a retrospective case-control study using patient-reported outcomes. SETTINGS: The study was conducted at a comprehensive cancer center. PATIENTS: Twenty-one patients underwent a watch-and-wait approach and were matched 1:1 with 21 patients from a pool of 190 patients who underwent sphincter-preserving surgery, based on age, sex, and tumor distance from the anal verge. MAIN OUTCOME MEASURES: Bowel function was measured using the Memorial Sloan Kettering Cancer Center Bowel Function Instrument. RESULTS: Patients in the watch-and-wait arm had better bowel function on the overall scale (median total score, 76 vs 55; p < 0.001) and on all of the subscales, with the greatest difference on the urgency/soilage subscale (median score, 20 vs 12; p < 0.001). LIMITATIONS: The study was limited by its retrospective design, small sample size, and temporal variability between surgery and time of questionnaire completion. CONCLUSIONS: A watch-and-wait strategy correlated with overall better bowel function when compared with sphincter-preserving surgery using a comprehensive validated bowel dysfunction tool. See Video Abstract at http://links.lww.com/DCR/B218. FUNCIÓN EVACUATORIA INFORMADA POR PACIENTES EN CÁNCER RECTAL MANEJADO CON UNA ESTRATEGIA DE OBSERVAR Y ESPERAR DESPUÉS DE LA TERAPIA NEOADYUVANTE: UN ESTUDIO DE CASOS Y CONTROLES: Observar y esperar es una alternativa no operativa a la cirugía de preservación del esfínter para pacientes con cáncer rectal localmente avanzado que logran una respuesta clínica completa después de la terapia neoadyuvante. Hay datos limitados sobre la función evacuatoria en pacientes sometidos a este abordaje para preservación de órganos.Evaluar la función evacuatoria en pacientes con cáncer rectal manejados con observar y esperar comparado a pacientes sometidos a cirugía de preservación de esfínteres (escisión mesorrectal total).Estudio retrospectivo de casos y controles utilizando resultados reportados por pacientes.Centro especializado oncológico.21 pacientes se sometieron a observar y esperar y se compararon con 21 pacientes de un grupo de 190 pacientes que se sometieron a cirugía de preservación de esfínteres controlando por edad, sexo y la distancia del tumor al borde anal.Función evacuatoria utilizando un instrumento de valoración del Centro de Cáncer Memorial Sloan Kettering.Los pacientes de observar y esperar demostraron mejor función evacuatoria en la escala general (puntuación total media, 76 versus 55; p <0,001) y en todas las subescalas, con la mayor diferencia en la subescala de urgencia / ensuciamiento fecal (puntuación media, 20 versus 12; p <0,001).Diseño retrospectivo, numero de muestra pequeño y variabilidad temporal entre la cirugía y el tiempo de finalización del cuestionario.Observar y esperar se correlacionó con mejor función evacuatoria en general en comparación con la cirugía de preservación del esfínter utilizando una herramienta integral validada para la disfunción evacuatoria. Consulte Video Resumen en http://links.lww.com/DCR/B218. (Traducción-Dr. Adrián Ortega).

Risk of Metachronous Colorectal Neoplasm after a Segmental Colectomy in Lynch Syndrome Patients According to Mismatch Repair Gene Status.

BACKGROUND: Because of increased risk of metachronous colorectal cancer (CRC), all patients with Lynch syndrome (LS) are offered a total colectomy. However, because metachronous CRC rate by mismatch repair (MMR) gene is uncertain, and total colectomy negatively impacts quality of life, it remains unclear whether segmental resection is indicated for lower penetrance MMR genes. We evaluated metachronous CRC incidence according to MMR gene in LS patients who underwent a segmental colectomy. STUDY DESIGN: Single-center, retrospective cohort study in patients with an earlier colectomy for CRC and an MMR germline mutation in MLH1, MSH2, MSH6, or PMS2 followed prospectively in a hereditary CRC family registry. All patients underwent surveillance colonoscopy. Metachronous CRC was defined as one detected more than 1 year after index resection. Primary end point was cumulative incidence of metachronous CRC overall and by MMR gene. RESULTS: One hundred and ten patients were included: 35 with MLH1 likely pathogenic/pathogenic (LP/P) variants (32%), 42 MSH2 (38%), 20 MSH6 (18%), and 13 PMS2 (12%). Median follow-up 4.26 years (range 0.53 to 19.92 years). Overall, metachronous CRC developed in 22 patients (20%). At 10-year follow-up, incidence was 12% (95% CI 6% to 23%), with no metachronous CRC detected in patients with a PMS2 or MSH6 LP/P variant. CONCLUSIONS: After index segmental resection, metachronous CRC is less likely to develop in LS patients with MSH6 or PMS2 LP/P variant than in MLH1 or MSH2 carriers. Our data support segmental resection and long-term colonoscopic surveillance rather than total colectomy in carefully selected, well-informed LS patients with MSH6 or PMS2 LP/P variant.