Association of Lateral Pelvic Lymph Nodes with Disease Recurrence and Organ Preservation in Patients with Distal Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy.

OBJECTIVE: Assess the significance of enlarged lateral lymph nodes (LLN) for disease recurrence, metastasis, and organ preservation in patients with rectal cancer. BACKGROUND: Optimal treatment of rectal adenocarcinoma involving LLN is subject to debate. METHODS: A post hoc analysis of the OPRA trial, a multicenter study of patients with rectal cancer treated with total neoadjuvant therapy (TNT) followed by total mesorectal excision or watch-and-wait management. We analyzed the association of visible LLN (LLN+), LLN≥7 mm (short axis) on baseline MRI, and LLN≥4 mm on restaging MRI with recurrence, metastasis, and rectum preservation. RESULTS: At baseline, 57 out of 324 (18%) patients had LLN+. In 30 (53%) of 57 patients with LLN+ on baseline MRI, the LLN disappeared after TNT. Disease recurrence in LLN was rare (3.5% of patients with LLN+ and 0.4% of patients with LLN-). All patients with recurrence in LLN also had distant metastasis. The rate of organ preservation was significantly lower in patients with LLN≥4 mm on restaging MRI (P=0.013). We found no significant differences in rates of local recurrence or metastasis between patients with LLN+ vs. LLN- and in patients with LLN≥7 vs.<7 mm on baseline MRI. LLN dissection was performed in 3 patients; 2 of them died of distant metastasis. CONCLUSIONS: LLN involvement is not associated with disease recurrence or metastasis, but persistence of LLN≥4 mm after TNT is negatively associated with rectum preservation in patients with locally advanced rectal cancer treated with TNT. Dissection of lateral nodes likely benefits few patients.

Assessing Endoscopic Response in Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy: Development and Validation of a Highly Accurate Convolutional Neural Network.

BACKGROUND: Rectal tumors display varying degrees of response to total neoadjuvant therapy (TNT). We evaluated the performance of a convolutional neural network (CNN) in interpreting endoscopic images of either a non-complete response to TNT or local regrowth during watch-and-wait surveillance. METHODS: Endoscopic images from stage II/III rectal cancers treated with TNT from 2012 to 2020 at a single institution were retrospectively reviewed. Images were labelled as Tumor or No Tumor based on endoscopy timing (before, during, or after treatment) and the tumor's endoluminal response. A CNN was trained using ResNet-50 architecture. The area under the curve (AUC) was analyzed during training and for two test sets. The main test set included images of tumors treated with TNT. The other contained images of local regrowth. The model's performance was compared to sixteen surgeons and surgical trainees who evaluated 119 images for evidence of tumor. Fleiss' kappa was calculated by respondent experience level. RESULTS: A total of 2717 images from 288 patients were included; 1407 (51.8%) contained tumor. The AUC was 0.99, 0.98, and 0.92 for training, main test, and local regrowth test sets. The model performed on par with surgeons of all experience levels for the main test set. Interobserver agreement was good ( k = 0.71-0.81). All groups outperformed the model in identifying tumor from images of local regrowth. Interobserver agreement was fair to moderate ( k = 0.24-0.52). CONCLUSIONS: A highly accurate CNN matched the performance of colorectal surgeons in identifying a noncomplete response to TNT. However, the model demonstrated suboptimal accuracy when analyzing images of local regrowth.

Validation of a Clinical Calculator Predicting Freedom From Colon Cancer Recurrence After Surgery on the Basis of Molecular and Clinical Variables.

BACKGROUND: The Memorial Sloan Kettering clinical calculator for estimating the likelihood of freedom from colon cancer recurrence on the basis of clinical and molecular variables was developed at a time when testing for microsatellite instability was performed selectively, based on patient age, family history, and histologic features. Microsatellite stability was assumed if no testing was done. OBJECTIVE: This study aimed to validate the calculator in a cohort of patients who had all been tested for microsatellite instability. DESIGN: Retrospective cohort analysis. SETTINGS: Comprehensive cancer center. PATIENTS: This study included consecutive patients who underwent curative resection for stage I, II, or III colon cancer between 2017 and 2019. INTERVENTION: Universal testing of mircrosatellite phenotype in all cases. MAIN OUTCOME MEASURES: The calculator's predictive accuracy was assessed using the concordance index and a calibration plot of predicted versus actual freedom from recurrence at 3 years after surgery. For a secondary sensitivity analysis, the presence of a tumor deposit(s) (disease category N1c) was considered equivalent to one positive lymph node (category N1a). RESULTS: With a median follow-up of 32 months among survivors, the concordance index for the 745 patients in the cohort was 0.748 (95% CI, 0.693-0.801), and a plot of predicted versus observed recurrences approached the 45° diagonal, indicating good discrimination and calibration. In the secondary sensitivity analysis for tumor deposits, the concordance index was 0.755 (95% CI, 0.700-0.806). LIMITATIONS: This study was limited by its retrospective, single-institution design. CONCLUSIONS: These results, based on inclusion of actual rather than imputed microsatellite stability status and presence of tumor deposits, confirm the predictive accuracy and reliability of the calculator. See Video Abstract . VALIDACIN DE UNA CALCULADORA CLNICA QUE PREDICE LA AUSENCIA DE RECURRENCIA POSTQUIRURGICA DEL CNCER DE COLON SOBRE LA BASE DE VARIABLES MOLECULARES Y CLNICAS: ANTECEDENTES:La calculadora clínica del Memorial Sloan Kettering para la estimación de la probabilidad de ausencia de recurrencia del cáncer de colon sobre la base de variables clínicas y moleculares, se desarrolló en un momento en que las pruebas para la inestabilidad de microsatélites se realizaban de forma selectiva, basadas en la edad del paciente, los antecedentes familiares y las características histológicas. Se asumía la estabilidad micro satelital si no se realizaba ninguna prueba.OBJETIVO:El objetivo de este estudio fue validar la calculadora en una cohorte de pacientes a los que se les había realizado la prueba de inestabilidad de microsatélites.DISEÑO:Análisis de cohorte retrospectivo.AJUSTE:Centro integral de cáncer.PACIENTES:Pacientes consecutivos con cáncer de colon que fueron sometidos a resección curativa por cáncer de colon en estadios I, II o III entre los años 2017 y 2019.PRINCIPALES MEDIDAS DE RESULTADO:La precisión predictiva de la calculadora fue evaluada mediante el índice de concordancia y un gráfico de calibración de la ausencia de recurrencia predecida versus la real a los 3 años tras la cirugía. A los efectos de un análisis secundario de sensibilidad, la presencia de depósito(s) tumoral(es) (categoría de enfermedad N1c) se consideró equivalente a un ganglio linfático positivo (categoría N1a).RESULTADOS:Con una mediana de seguimiento de 32 meses entre los supervivientes, el índice de concordancia para los 745 pacientes de la cohorte fue de 0,748 (intervalo de confianza del 95 %, 0,693 a 0,801), y una gráfica de recurrencias previstas versus observadas se acercó a la diagonal de 45°, indicando una buena discriminación y calibración. En el análisis secundario de sensibilidad para depósitos tumorales, el índice de concordancia fue de 0,755 (intervalo de confianza del 95 %, 0,700 a 0,806).LIMITACIONES:Diseño retrospectivo, institución única.CONCLUSIONES:Estos resultados, basados en la inclusión real del estado de estabilidad de microsatélites en lugar de imputado y la presencia de depósitos tumorales, confirman la precisión predictiva y la confiabilidad de la calculadora. (Traducción-Dr Osvaldo Gauto ).

Anal Adenocarcinoma Treated in the Era of Total Neoadjuvant Therapy and Nonoperative Management.

BACKGROUND: Anal adenocarcinoma bears a treatment strategy unique to other anal cancers. OBJECTIVE: This study aimed to describe oncologic outcomes of total neoadjuvant therapy followed by watch-and-wait approach for anal adenocarcinoma. DESIGN: Retrospective analysis. SETTINGS: This study was conducted at a comprehensive cancer center. PATIENTS: Patients with anal adenocarcinoma treated between 2004 and 2019 were selected. INTERVENTIONS: Fifty-four patients received neoadjuvant therapy and were divided into 2 groups according to their treatment strategy: total neoadjuvant therapy versus single neoadjuvant modality therapy. MAIN OUTCOME MEASURES: Organ preservation, tumor regrowth, local failure, distant metastasis rates, recurrence-free survival, and overall survival. RESULTS: This study included 70 patients with anal adenocarcinoma. Fifty-four patients (77%) received neoadjuvant therapy, of whom 30 (42%) received total neoadjuvant therapy and 24 (34%) received single neoadjuvant modality. Twenty-three (33%) patients achieved complete clinical response and were managed by watch-and-wait approach. The proportion of patients able to continue to watch-and-wait approach was higher after receiving total neoadjuvant therapy (60%) compared with single neoadjuvant modality therapy (20%; p = 0.004). A tumor regrowth rate of 22% was observed in the total neoadjuvant therapy group. The 5-year overall survival rate was 70% (95% CI, 59%-83%), including 61% (95% CI, 42%-88%) for the total neoadjuvant therapy and 65% (95% CI, 48%-88%) for the single neoadjuvant modality groups. Colostomy was avoided in 50% of patients who received total neoadjuvant therapy and 83% of watch-and-wait patients. Five-year recurrence-free survival rates of 55% (95% CI, 39%-79%) and 30% (95% CI, 15%-58%) were observed in the total neoadjuvant therapy and single neoadjuvant modality groups. LIMITATIONS: Retrospective nature. CONCLUSIONS: This is the first report in the literature describing the safety and feasibility of nonoperative management for anal adenocarcinoma. Anal adenocarcinoma treated with total neoadjuvant therapy and nonoperative management achieve regrowth rates comparable to those observed in rectal cancer, with oncologic outcomes similar to those of traditional treatment strategies. See Video Abstract . ADENOCARCINOMA ANAL TRATADO EN LA ERA DE LA TERAPIA NEOADYUVANTE TOTAL Y EL TRATAMIENTO NO QUIRRGICO: ANTECEDENTES:El adenocarcinoma anal conlleva una estrategia de tratamiento único para otros cánceres anales.OBJETIVO:Describir los resultados oncológicos de la terapia neoadyuvante total seguida de observar y esperar en adenocarcinoma anal.DISEÑO:Análisis retrospectivo.AJUSTE:Este estudio se llevó a cabo en un centro oncológico integral.PACIENTES:Se seleccionaron pacientes con adenocarcinoma anal tratados entre 2004-2019.INTERVENCIONES:Cincuenta y cuatro pacientes recibieron terapia neoadyuvante y se dividieron en dos grupos según su estrategia de tratamiento: terapia neoadyuvante total versus terapia de modalidad neoadyuvante única.PRINCIPALES MEDIDAS DE RESULTADO:Preservación de órganos, recurrencia tumoral, falla local, tasas de metástasis a distancia, libre de recurrencia y supervivencia general.RESULTADOS:El estudio incluyó a 70 pacientes con adenocarcinoma anal. Cincuenta y cuatro pacientes (77%) recibieron terapia neoadyuvante, de los cuales 30 (42%) recibieron terapia neoadyuvante total y 24 (34%) recibieron modalidad neoadyuvante única. Veintitrés (33%) pacientes presentaron una respuesta clínica completa y fueron tratados con vigilancia y espera. La proporción de pacientes capaces de continuar en observar y esperar fue mayor después de recibir terapia neoadyuvante total (60%) en comparación con la terapia de modalidad neoadyuvante única (20%) ( p = 0,004). Se observó una tasa de recurrencia tumoral del 22% en el grupo de terapia neoadyuvante total. La tasa de supervivencia general a 5 años fue del 70% (IC95% 59%-83 %), incluido el 61% (IC95% 42%-88%) para la terapia neoadyuvante total y el 65% (IC95% 48%-88%) para grupos de modalidad neoadyuvante única. Se evitó la colostomía en el 50% de los pacientes que recibieron terapia neoadyuvante total y el 83% de los pacientes en observar y esperar. Se observaron tasas de supervivencia libre de recurrencia a cinco años del 55% (IC95% 39%-79%) y del 30% (IC95% 15%-58%) en los grupos de terapia neoadyuvante total y modalidad neoadyuvante única, respectivamente.LIMITACIONES:Diseño retrospectivo.CONCLUSIONES:Este es el primer informe en la literatura que describe la seguridad y viabilidad del tratamiento no quirúrgico del adenocarcinoma anal. El adenocarcinoma anal tratado con terapia neoadyuvante total y manejo no quirúrgico logra tasas de recurrencia comparables a las observadas en el cáncer de recto, con resultados oncológicos similares a las estrategias de tratamientos tradicionales. (Traducción-Dr. Fidel Ruiz Healy ).

Development and perception of surgery-specific goals of care discussions in the preoperative setting: A learning pilot.

BACKGROUND: Goals of care discussions are infrequently documented in the preoperative period. Furthermore, documentation does not consistently address what matters most to patients, although patient values (PV) are central to person-centered care. METHODS: A multidisciplinary working group was formed. An electronic note comprised of (1) topics of discussion, (2) PV, and (3) advance care planning (ACP), was created and embedded into existing note templates for Gynecologic Surgical Oncology. Surgeons and advanced practice providers (APPs) were educated to conduct and document these conversations in preoperative clinic for patients undergoing cancer surgery for a pilot period. Data were collected regarding usage of the template. Focus groups with surgeons, APPs, and patients were conducted. Qualitative analysis was performed on transcripts. RESULTS: During the pilot, 7 surgeon/APP teams utilized the template on a total of 55 notes. Average number of notes completed per surgeon was 7.8 (SD 8.5). Forty-six notes (84%) included topics of discussion, 15 (27%) included PV, 4 (7%) included ACP. Qualitative analysis of focus group transcripts revealed that clinicians and patients perceived the initiative to be useful and important, although implementation barriers were identified. CONCLUSION: Creating a surgery-specific GOC template is feasible. Iterative revisions are needed to increase utility in clinic workflows.

Tumour deposits are independently associated with recurrence in colon cancer.

AIM: Tumour deposits are focal aggregates of cancer cells in pericolic fat and mesentery, distinct from vessels, nerves and lymphatics. Their presence upstages lymph node negative patients but is ignored in lymph node positive patients. We investigated the clinicopathological factors associated with tumour deposits and their impact on recurrence in lymph node positive and negative patients. METHOD: Clinicopathological variables were collected from the medical records of patients with Stage I-III colon cancer who underwent resection in 2017-2019. Pathology was reviewed by a gastrointestinal pathologist. Patients with rectal cancer, metastasis, and concurrent malignancy were excluded. RESULTS: Tumour deposits were noted in 69 (9%) of 770 patients. They were associated with the presence of lymph node metastasis, advanced T category, poorly differentiated tumours, microsatellite stable subtype and lymphovascular and perineural invasion (p < 0.05). The presence of tumour deposits (hazard ratio 2.48, 95% CI 1.49-4.10) and of lymph node metastasis (hazard ratio 3.04, 95% CI 1.72-5.37) were independently associated with decreased time to recurrence. There was a weak correlation (0.27) between the number of tumour deposits and the number of positive lymph nodes. CONCLUSION: Tumour deposits are associated with more advanced disease and high-risk pathological features. The presence of tumour deposits and lymph node metastasis were found to be independent risk factors for decreased time to recurrence. A patient with both lymph node metastasis and tumour deposits is more than twice as likely to have recurrence compared with a patient with only lymph node metastasis. Tumour deposits independently predict recurrence and should not be ignored in lymph node positive patients.

Lymph Node Metastases and Associated Recurrence-Free Survival in Microsatellite Stable and Unstable Colon Cancer.

BACKGROUND: In contrast to microsatellite stable (MSS) colon cancer, predictors of lymph node metastases and their association with recurrence are not well-defined in microsatellite instability (MSI) colon cancer. METHODS: A cohort of nonmetastatic colon cancer patients undergoing surgery between 2015 and 2021 were evaluated for predictors of lymph node metastases (LNMs) and their association with recurrence-free survival (RFS). RESULTS: Of 1466 patients included in the analyses, 361 (25 %) had MSI. Compared with MSS, MSI was associated with earlier stage, fewer LNMs in the patients with N1 or N2 disease, and fewer high-risk features. Compared with the T3-T4 MSS patients, the odds ratios for LNM were 0.52 (95% confidence interval [CI], 0.38-0.71) for the T3-T4 MSI patients, 0.27 (95% CI, 0.38-0.71) for the T1-T2 MSS patients, and 0.15 (95 % CI, 0.08-0.26) for the T1-T2 MSI patients. In both groups, LNMs were associated with T category, patient age, and venous, lymphatic, or perineural invasion. In the MSS patients, LNMs were additionally associated with patient sex and histologic grade. Compared with the MSS patients, the MSI patients with N0 and N1 disease had a better 3-year RFS. However, the MSI patients with N2 disease had a lower rate of 3-year RFS than the MSS patients (hazard ratio, 19.75 vs 4.49). CONCLUSIONS: In MSI colon cancer, LNMs are 50 % less prevalent, but the factors associated with LNM are like those in MSS colon cancer. The improved prognosis traditionally associated with early-stage MSI colon cancers dissipates with four or more LNMs. These findings should be taken into consideration by clinicians selecting the most appropriate course of treatment for MSI colon cancer.

MRI Assessment of Extramural Venous Invasion Before and After Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer and Its Association with Disease-Free and Overall Survival.

BACKGROUND: Extramural venous invasion (EMVI) on baseline MRI is associated with poor prognosis in patients with locally advanced rectal cancer. This study investigated the association of persistent EMVI after total neoadjuvant therapy (TNT) (chemoradiotherapy and systemic chemotherapy) with survival. METHODS: Baseline MRI, post-TNT MRI, and surgical pathology data from 175 patients with locally advanced rectal cancer who underwent TNT and total mesorectal excision between 2010 and 2017 were retrospectively analyzed for evidence of EMVI. Two radiologists assessed EMVI status with disagreement adjudicated by a third. Pathologic EMVI status was assessed per departmental standards. Cox regression models evaluated the associations between EMVI and disease-free and overall survival. RESULTS: EMVI regression on both post-TNT MRI and surgical pathology was associated with disease-free survival (hazard ratio, 0.17; 95% confidence interval (CI), 0.04-0.64) and overall survival (hazard ratio, 0.11; 95% CI, 0.02-0.68). In an exploratory analysis of 35 patients with EMVI on baseline MRI, only six had EMVI on pathology compared with 18 on post-TNT MRI; these findings were not associated (p = 0.2). Longer disease-free survival was seen with regression on both modalities compared with remaining positive. Regression on pathology alone, independent of MRI EMVI status, was associated with similar improvements in survival. CONCLUSIONS: Baseline EMVI is associated with poor prognosis even after TNT. EMVI regression on surgical pathology is common even with persistent EMVI on post-TNT MRI. EMVI regression on surgical pathology is associated with improved DFS, while the utility of post-TNT MRI EMVI persistence for decision-making and prognosis remains unclear.

Comparison of Robotic, Laparoscopic, and Open Resections of Nonmetastatic Colon Cancer.

BACKGROUND: Laparoscopic resection for colon cancer has not been associated with improvements in oncological outcomes in comparison to open resection. Robotic resections are associated with increased lymph node yield and radicality of mesenteric resection in patients with right-sided tumors. It is unclear whether lymph node yield is higher in robotic resections in other parts of the colon and whether higher lymph node yield is associated with improved survival. OBJECTIVE: To compare survival rates between robotic, laparoscopic, and open resections in a large cohort of patients with nonmetastatic colon cancer. DESIGN: This is a retrospective observational study. SETTING: A single comprehensive cancer center. PATIENTS: Patients who underwent resection of nonmetastatic primary colon cancer between January 2006 and December 2018. MAIN OUTCOME MEASURES: Univariable and multivariable models were used to identify predictors of disease-free and overall survival. Lymph node yield and perioperative outcomes were compared between operative approaches. RESULTS: There were 2398 patients who met the inclusion criteria: 699 (29%) underwent open, 824 (34%) underwent laparoscopic, and 875 (36%) underwent robotic resection. The median follow-up was 3.8 years (45.4 months). Robotic surgery was associated with higher lymph node yield and radicality of mesenteric resection. On multivariable analysis, the surgical approach was not associated with a difference in disease-free or overall survival. Minimally invasive colectomy was associated with fewer complications and shorter length of stay in comparison to open surgery. In a direct comparison between the 2 minimally invasive approaches, robotic colectomy was associated with fewer complications, shorter length of stay, and lower conversion rate than laparoscopy. LIMITATIONS: This was a single-center retrospective study. CONCLUSIONS: Our data indicate that the 3 surgical approaches are similarly effective in treating primary resectable colon cancer and that differences in outcomes are observed primarily in the early postoperative period. See Video Abstract at http://links.lww.com/DCR/C115 . COMPARACIN DE RESECCIONES ROBTICAS, LAPAROSCPICAS Y ABIERTAS DE CNCER DE COLON NO METASTSICO: ANTECEDENTES:La resección laparoscópica para el cáncer de colon no se ha asociado con mejoras en los resultados oncológicos en comparación con la resección abierta. Las resecciones robóticas se asocian con un mayor rendimiento de los ganglios linfáticos y la radicalidad de la resección mesentérica en pacientes con tumores del lado derecho. No está claro si la cosecha ganglionar es mayor en las resecciones robóticas en otras partes del colon y si un mayor rendimiento de los ganglios linfáticos se asocia con una mejor supervivencia.OBJETIVO:Comparar las tasas de supervivencia entre resecciones robóticas, laparoscópicas y abiertas en una gran cohorte de pacientes con cáncer de colon no metastásico.DISEÑO:Este es un estudio observacional retrospectivo.ESCENARIO:Este estudio se realizó en un único centro oncológico integral.PACIENTES:Pacientes que se sometieron a resección de cáncer de colon primario no metastásico entre enero de 2006 y diciembre de 2018.PRINCIPALES MEDIDAS DE RESULTADO:Se utilizaron modelos univariables y multivariables para identificar predictores de supervivencia libre de enfermedad y global. La cosecha ganglionar y los resultados perioperatorios se compararon entre los abordajes quirúrgicos.RESULTADOS:Hubo 2398 pacientes que cumplieron con los criterios de inclusión: 699 (29%) se sometieron a cirugía abierta, 824 (34%) se sometieron a resección laparoscópica y 875 (36%) se sometieron a resección robótica. La mediana de seguimiento fue de 3,8 años (45,4 meses). La cirugía robótica se asoció con una mayor cosecha ganglionar y la radicalidad de la resección mesentérica. En el análisis multivariable, el abordaje quirúrgico no se asoció con una diferencia en la supervivencia general o libre de enfermedad. La colectomía mínimamente invasiva se asoció con menos complicaciones y una estancia más corta en comparación con la cirugía abierta. En una comparación directa entre los dos enfoques mínimamente invasivos, la colectomía robótica se asoció con menos complicaciones, una estancia más corta y una tasa de conversión más baja que la laparoscopia.LIMITACIONES:Este fue un estudio retrospectivo de un solo centro.CONCLUSIONES:Nuestros datos indican que los tres enfoques quirúrgicos son igualmente efectivos en el tratamiento del cáncer de colon resecable primario y que las diferencias en los resultados se observan principalmente en el período posoperatorio temprano. Consulte Video Resumen en http://links.lww.com/DCR/C115 . (Traducción-Dr. Felipe Bellolio ).

Incomplete cytoreductive surgery for appendiceal and colorectal peritoneal carcinomatosis: Characteristics and outcomes of an overlooked group.

BACKGROUND OND OBJECTIVES: Complete cytoreductive surgery (CRS) may prolong survival for selected patients with peritoneal carcinomatosis from colorectal cancer (CRC). However, there is a paucity of data on outcomes following incomplete procedures. METHODS: Patients with incomplete CRS for well-differentiated (WD) and moderate/poorly-differentiated (M/PD) appendiceal cancer, right and left CRC were identified at a single tertiary center (2008-2021). RESULTS: Of 109 patients, 10% were WD and 51% M/PD appendiceal cancers, and 16% right and 23% left CRC. There were no differences in gender, BMI (mean = 27), ASA score, previous abdominal surgery (72%), and extent of CRS. The PC Index differed between appendiceal and colorectal cancers (mean = 27 vs. 17, p < 0.01). Overall, the perioperative outcomes were similar among the groups, with 15% experiencing complications. Postoperatively, 61% received chemotherapy, and 51% required ≥1 subsequent procedure. The 1 and 3-year survival for the WD, M/PD, right and left CRC subgroups were 100%, 67%, 44%, 51%, and 88%, 17%, 12%, and 23%, respectively (p = 0.02). CONCLUSIONS: Incomplete CRS was associated with significant morbidity and number of subsequent palliative procedures. Prognosis correlated with histologic subtype; WD appendiceal cancer patients having superior outcomes, while those with right sided CRC the worst survival. These data may help guiding expectations in the setting of incomplete procedures.

EWSR1::YY1 fusion positive peritoneal epithelioid mesothelioma harbors mesothelioma epigenetic signature: Report of 3 cases in support of an emerging entity.

Mesothelioma is a rare, aggressive malignant neoplasm of mesothelial origin. A small subset of peritoneal mesothelioma is driven by recurrent gene fusions, mostly EWSR1/FUS::ATF1 fusions, with predilection for young adults. To date, only two cases of mesothelioma harboring EWSR1::YY1 fusions have been described. We present three additional cases of EWSR1::YY1-fused peritoneal mesotheliomas, two localized and one diffuse, all occurring in the peritoneum of middle-aged adults (2 females and 1 male), and discovered incidentally by imaging or during surgery performed for unrelated reasons. None presented with symptoms or had a known history of asbestos exposure. All three cases were cellular epithelioid neoplasms with heterogeneous architectural patterns comprising mostly solid nests and sheets with variably papillary and trabecular areas against collagenous stroma. Cytologically, the cells were monomorphic, polygonal, epithelioid cells with dense eosinophilic cytoplasm and centrally located nuclei. Overt mitotic activity or tumor necrosis was absent. All cases showed strong diffuse immunoreactivity for pancytokeratin, CK7, and nuclear WT1, patchy to negative calretinin, retained BAP1 expression, and were negative for Ber-EP4 and MOC31. RNA-sequencing confirmed in-frame gene fusion transcripts involving EWSR1 exon 7/8 and YY1 exon 2/3. By unsupervised clustering analysis, the methylation profiles of EWSR1::YY1-fused mesotheliomas clustered similarly with EWSR1/FUS::ATF1-fused mesotheliomas and conventional mesotheliomas, suggesting a mesothelioma epigenetic signature. All three patients underwent surgical resection or cytoreductive surgery of the masses. On follow-up imaging, no recurrence or progression of disease was identified. Our findings suggest that EWSR1::YY1-fusion defines a small subset of peritoneal epithelioid mesothelioma in middle-aged adults without history of asbestos exposure.

Survival After Induction Chemotherapy and Chemoradiation Versus Chemoradiation and Adjuvant Chemotherapy for Locally Advanced Rectal Cancer.

BACKGROUND: Total neoadjuvant therapy (TNT) improves tumor response in locally advanced rectal cancer (LARC) patients compared to neoadjuvant chemoradiotherapy alone. The effect of TNT on patient survival has not been fully investigated. MATERIALS AND METHODS: This was a retrospective case series of patients with LARC at a comprehensive cancer center. Three hundred and eleven patients received chemoradiotherapy (chemoRT) as the sole neoadjuvant treatment and planned adjuvant chemotherapy, and 313 received TNT (induction fluorouracil and oxaliplatin-based chemotherapy followed by chemoradiotherapy in the neoadjuvant setting). These patients then underwent total mesorectal excision or were entered in a watch-and-wait protocol. The proportion of patients with complete response (CR) after neoadjuvant therapy (defined as pathological CR or clinical CR sustained for 2 years) was compared by the χ2 test. Disease-free survival (DFS), local recurrence-free survival, distant metastasis-free survival, and overall survival were assessed by Kaplan-Meier analysis and log-rank test. Cox regression models were used to further evaluate DFS. RESULTS: The rate of CR was 20% for chemoRT and 27% for TNT (P=.05). DFS, local recurrence-free survival, metastasis-free survival, and overall survival were no different. Disease-free survival was not associated with the type of neoadjuvant treatment (hazard ratio [HR] 1.3; 95% confidence interval [CI] 0.93-1.80; P = .12). CONCLUSIONS: Although TNT does not prolong survival than neoadjuvant chemoradiotherapy plus intended postoperative chemotherapy, the higher response rate associated with TNT may create opportunities to preserve the rectum in more patients with LARC.

Adoption of Organ Preservation and Surgeon Variability for Patients with Rectal Cancer Does Not Correlate with Worse Survival.

BACKGROUND AND OBJECTIVES: Watch-and-wait is variably adopted by surgeons and the impact of this on outcomes is unknown. We compared the disease-free survival and organ preservation rates of locally advanced rectal cancer patients treated by expert colorectal surgeons at a comprehensive cancer center. METHODS: This study included retrospective data on patients diagnosed with stage II/III rectal adenocarcinoma from January 2013 to June 2017 who initiated neoadjuvant therapy (either with chemoradiation, chemotherapy, or a combination of both) and were treated by an expert colorectal surgeon. RESULTS: Overall, 444 locally advanced rectal cancer patients managed by five surgeons were included. Tumor distance from the anal verge, type of neoadjuvant therapy, and organ preservation rates varied by treating surgeon. There was no difference in disease-free survival after stratifying by the treating surgeon (p = 0.2). On multivariable analysis, neither the type of neoadjuvant therapy nor the treating surgeon was associated with disease-free survival. CONCLUSIONS: While neoadjuvant therapy type and organ preservation rates varied among surgeons, there were no meaningful differences in disease-free survival. These data suggest that among expert colorectal surgeons, differing thresholds for selecting patients for watch-and-wait do not affect survival.

MRI at Restaging After Neoadjuvant Therapy for Rectal Cancer Overestimates Circumferential Resection Margin Proximity as Determined by Comparison With Whole-Mount Pathology.

BACKGROUND: Current guidelines recommend restaging with MRI after neoadjuvant therapy for rectal cancer, but the accuracy of restaging MRI in estimating circumferential margin involvement requires additional clarification. OBJECTIVE: The objective of this study was to measure the accuracy of circumferential resection margin assessment by MRI after neoadjuvant therapy and identify characteristics associated with accuracy. DESIGN: MRI data were retrospectively analyzed for concordance with the findings of whole-mount pathology analysis of the corresponding surgical specimens. Univariate and multivariate logistic regression analyses were performed to identify characteristics associated with accuracy. SETTING: This study was conducted at a comprehensive cancer center. PATIENTS: Included in the study were consecutive patients who underwent total mesorectal excision for rectal cancer between January 2018 and March 2020 after receiving neoadjuvant therapy and undergoing restaging with MRI. MAIN OUTCOME MEASURES: The primary outcome of this study included accuracy, sensitivity, specificity, and positive and negative predictive values for categorizing the circumferential resection margin as threatened; mean and paired mean differences were in proximity of the margin. RESULTS: Of the 94 patients included in the analysis, 39 (41%) had a threatened circumferential resection margin according to MRI at restaging, but only 17 (18%) had a threatened margin based on pathology. The accuracy of MRI in identifying a threatened margin was 63.8%, with margin proximity overestimated by 0.4 cm on average. In multivariate logistic regression, anterior location of the margin and tumor proximity to the anal verge were independently associated with reduced MRI accuracy. LIMITATIONS: A limitation was the retrospective design at a single institution. CONCLUSIONS: The knowledge that MRI-based restaging after neoadjuvant therapy overestimates circumferential margin proximity may render some surgical radicality unnecessary and thereby help avoid the associated morbidity. With the recognition that MRI-based assessment of margin proximity may not be reliable for anterior margin and for distal tumors, radiologists may want to use greater caution in interpreting images of tumors with these characteristics and to acknowledge the uncertainty in their reports. See Video Abstract at http://links.lww.com/DCR/B814. LA IRM EN LA REESTADIFICACIN LUEGO DE TERAPIA NEOADYUVANTE EN EL CNCER DE RECTO SOBRESTIMA LA PROXIMIDAD DEL MARGEN DE RESECCIN CIRCUNFERENCIAL SEGN LO DETERMINADO COMPARATIVAMENTE CON LA PIEZA DE ANATOMOPATOLOGA: ANTECEDENTES:Las pautas actuales recomiendan la re-estadificación por medio de la resonancia magnética luego de terapia neoadyuvante en los casos de cáncer de recto, pero la precisión de la reevaluación con la IRM para estimar el grado de implicación del margen circunferencial requiere aclaraciones adicionales.OBJETIVO:Medir el grado de exactitud en la evaluación del margen de resección circunferencial mediante resonancia magnética después de la terapia neoadyuvante e identificar las características asociadas con la precisión.DISEÑO:Se analizaron retrospectivamente los datos de resonancia magnética para determinar la concordancia entre los hallazgos del análisis de la pieza de anatamopatología y las muestras quirúrgicas correspondientes. Se realizó el análisis de regresión logística univariada y multivariada para identificar las características asociadas con la exactitud.AJUSTE:Centro oncológico integral.PACIENTES:Todos aquellos que se sometieron consecutivamente a una excisión total del mesorrecto por cáncer rectal entre Enero 2018 y Febrero 2020 luego de recibir terapia neoadyuvante y someterse a una re-estadificación por imágenes de resonancia magnética (IRM).PRINCIPALES MEDIDAS DE RESULTADO:La exactitud, la sensibilidad y especificidad; los valores predictivos positivos y negativos para categorizar el margen de resección circunferencial como amenazado; la diferencia media y las medias pareadas de proximidad a los margenes.RESULTADOS:De los 94 pacientes incluidos en el análisis, 39 (41%) tenían un margen de resección circunferencial amenazado según la resonancia magnética en la re-estadificación, pero solo 17 (18%) tenían un margen amenazado basado en la patología. La precisión de la resonancia magnética para identificar un margen amenazado fue del 63,8%, con la proximidad del margen sobreestimada en 0,4 cm en promedio. En la regresión logística multivariada, la ubicación anterior de los bordes de resección y la proximidad del tumor al margen anal se asociaron de forma independiente con la reducción en la precisión de la resonancia magnética.LIMITACIONES:Diseño retrospectivo en una institución única.CONCLUSIONES:El saber que la re-estadificación basada en la IRM, luego de terapia neoadyuvante sobreestima la proximidad de la lesión a los márgenes circunferenciales, hace innecesaria cierta radicalidad quirúrgica complementaria, lo que ayuda a evitar morbilidad asociada. Reconociendo que la evaluación de proximidad de los márgenes de resección basada en la resonancia magnética, no puede ser confiable en casos de márgenes anteriores y en casos de tumores distales. Los radiólogos recomiendan tener más precaución en la interpretación de imágenes de tumores con estas características y reconocen cierto desasosiego en sus informes. Consulte Video Resumen en http://links.lww.com/DCR/B814.

Assessment of Patient-Reported Outcomes in Patients With Anal Squamous-Cell Cancer Undergoing Combined Modality Therapy.

BACKGROUND: There is limited knowledge on long-term bowel, sexual, and urinary function after combined modality therapy for anal squamous-cell cancer. OBJECTIVE: This study aimed to evaluate long-term changes in patients treated with combined modality. DESIGN: This was a retrospective study of prospectively collected patient-reported outcome surveys. SETTING: This study was conducted at a single institution. PATIENTS: There were 143 patients with stage I to III anal cancer who were treated with chemoradiation and had completed the survey. MAIN OUTCOME MEASURES: This study included patient-reported outcomes reflecting bowel, sexual, and urinary function. RESULTS: Thirty-nine percent of patients had major low anterior resection syndrome at baseline. Major low anterior resection syndrome remained stable (38%; 95% CI, 31%-46%) with no change over time (OR 0.95; 95% CI, 0.74-1.21; p = 0.7). Higher rates of major low anterior resection syndrome were observed for patients who had major low anterior resection syndrome at baseline (OR 20.7; 95% CI 4.70-91.3; p < 0.001) and for females (OR 2.14; 95% CI, 1.01-4.56; p = 0.047). On 5-point scales, we saw a nonsignificant increased level of sexual arousal during sexual activity after therapy for women (ß for 1 year = 0.15; 95% CI, -0.01 to 0.32; p = 0.072) and nonsignificant decreased confidence in getting and keeping an erection after therapy for men (ß for 1 year = -0.33; 95% CI, -0.66 to 0.00; p = 0.053). LIMITATIONS: This was a single-institution study and only patients who answered the questionnaire were included in the study. CONCLUSIONS: A significant proportion of patients have major low anterior resection syndrome at baseline and after successful treatment for anal cancer. Having major low anterior resection syndrome at baseline was the biggest predictor of having major low anterior resection syndrome after treatment. Bowel, sexual, and urinary function did not improve over time up to 2 years after end of treatment. Physicians should counsel their patients before treatment that baseline poor bowel function is a risk factor for posttreatment bowel dysfunction. See Video Abstract at http://links.lww.com/DCR/C29 . EVALUACIN DE LOS RESULTADOS INFORMADOS POR LOS PACIENTES CON CNCER ANAL DE CLULAS ESCAMOSAS QUE SE SOMETEN A UNA TERAPIA DE MODALIDAD COMBINADA: ANTECEDENTES:Existe un conocimiento limitado sobre la función intestinal, sexual y urinaria a largo plazo después de la terapia de modalidad combinada para el cáncer anal de células escamosas.OBJETIVO:Evaluar los cambios a largo plazo en la función intestinal, sexual y urinaria en pacientes tratados con modalidad combinada.DISEÑO:Este fue un estudio retrospectivo de encuestas de resultados informadas por pacientes recolectadas prospectivamente.ESCENARIO:Institución única.PACIENTES:Fueron 143 pacientes con cáncer anal en estadio I-III que fueron tratados con quimiorradiación y completaron la encuesta.PRINCIPALES MEDIDAS DE RESULTADO:Resultados reportados por el paciente que reflejan la función intestinal, sexual, y urinaria.RESULTADOS:Treinta y nueve por ciento de los pacientes tenían puntajes importantes de síndrome de resección anterior bajo al inicio del estudio. Las puntuaciones del síndrome de resección anterior baja mayor permanecieron estables (38 %; IC del 95%: 31 %, 46 %) sin cambios con el tiempo (OR 0,95, IC del 95%: 0,74, 1,21, p = 0,7). Se observaron tasas más altas de puntuaciones del síndrome de resección anterior baja mayor para los pacientes que tenían puntuaciones del síndrome de resección anterior baja mayor desde el inicio (OR 20,7; IC del 95%: 4,70; 91,3, p < 0,001) y para las mujeres (OR 2,14; IC del 95%: 1,01, 4,56; p = 0,047). En escalas de 5 puntos, observamos un aumento no significativo del nivel de excitación sexual durante la actividad sexual después de la terapia para las mujeres (ß durante 1 año = 0,15; IC del 95%: -0,01, 0,32; p = 0,072) y una disminución no significativa de la confianza en lograr y mantener una erección después de la terapia para hombres (ß para 1 año = -0,33; IC del 95%: -0,66, 0,00; p = 0,053).LIMITACIONES:Este es un estudio de una sola institución. Solo se incluyeron en el estudio los pacientes que contestaron el cuestionario.CONCLUSIONES:Una proporción significativa de pacientes tienen puntajes de síndrome de resección anterior muy bajos al inicio del estudio y después de un tratamiento exitoso para el cáncer anal. Tener puntajes de síndrome de resección anterior bajos importantes al inicio del estudio fue el predictor más importante de tener puntajes de síndrome de resección anterior bajos importantes después del tratamiento. La función intestinal, sexual y urinaria no mejoró con el tiempo hasta 2 años después de finalizar el tratamiento. Los médicos deben aconsejar a sus pacientes antes del tratamiento que la mala función intestinal inicial es un factor de riesgo para la disfunción intestinal posterior al tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/C29 . (Traducción-Dr. Yolanda Colorado ).

Predictors of operative difficulty in robotic low anterior resection for rectal cancer.

AIM: This study evaluates the relationship of tumour and anatomical features with operative difficulty in robotic low anterior resection performed by four experienced surgeons in a high-volume colorectal cancer practice. METHODS: Data from 382 patients who underwent robotic low anterior resection by four expert surgeons between January 2016 and June 2019 were included in the analysis. Operating time was used as a measure of operative difficulty. Univariate and multivariate mixed models were used to identify associations between baseline characteristics and operating time, with surgeon as a random effect, thereby controlling for variability in surgeon speed and proficiency. In an exploratory analysis, operative difficulty was defined as conversion to laparotomy, a positive margin or an incomplete mesorectum. RESULTS: Median operating time was 4.28 h (range 1.95-11.33 h) but varied by surgeon from 3.45 h (1.95-6.10 h) to 5.93 h (3.33-11.33 h) (P < 0.001). Predictors of longer operating time in multivariate analysis were male sex, higher body mass index, neoadjuvant radiotherapy, low tumour height, greater sacral height and larger mesorectal area at the S5 vertebral level. Conversion occurred in two cases (0.5%), and incomplete mesorectum and positive margins were found in nine (2.4%) and 19 (5.0%) patients, respectively. Neoadjuvant radiotherapy and larger pelvic outlet were the only characteristics associated with the exploratory measure of difficulty. CONCLUSION: Predicting operative difficulty based on easy to identify, preoperative radiological and clinical variables is feasible in robotic anterior resection.

Primary Tumor Location and Outcomes After Cytoreductive Surgery and Intraperitoneal Chemotherapy for Peritoneal Metastases of Colorectal Origin.

BACKGROUND: The aim of this study is to evaluate outcomes in patients with peritoneal metastasis of colorectal cancer (pmCRC) who underwent cytoreductive surgery and intraperitoneal chemotherapy (CRS/IPC) in relation to the location of the primary tumor. Regional therapy, including cytoreductive surgery and intraperitoneal chemotherapy, has been associated with improved survival in patients with pmCRC. Location of the primary tumor has been shown to be prognostic in patients with metastasis. PATIENTS AND METHODS: A retrospective review was performed for all patients who underwent complete cytoreduction and intraperitoneal chemotherapy from 2010 to 2017, examining patient and tumor characteristics, overall and recurrence-free survival, recurrence patterns, and tumor mutational profiles. RESULTS: Ninety-three patients were included in the study: 49 (53%) with a right-sided and 44 (47%) with a left-sided primary tumor. Patients with a right-sided tumor had significantly shorter recurrence-free survival (median, 6.3 months; 95% CI, 4.7-8.1 months vs 12.3 months; 95% CI, 3.6-21.7 months; P = 0.02) and overall survival (median, 36.6 months; 95% CI, 26.4-46.9 months vs 83.3 months; 95% CI 44.2-122.4 months; P = 0.03). BRAF and KRAS mutations were more frequent in right-sided tumors, and APC and TP53 mutations were more frequent in left-sided tumors, which were more chromosomally instable. BRAF mutations were associated with early recurrence. CONCLUSIONS: Tumor sidedness is a predictor of oncological outcomes after CRS/IPC. Tumor sidedness and molecular characteristics should be considered when counseling patients regarding expected outcomes and when selecting or stratifying pmCRC patients for clinical trials of regional therapy.

Evaluating the Validity of the Clavien-Dindo Classification in Colectomy Studies: A 90-Day Cost of Care Analysis.

BACKGROUND: The Clavien-Dindo classification is widely used to report postoperative morbidity but may underestimate the severity of colectomy complications. OBJECTIVE: The purpose of this study was to assess how well the Clavien-Dindo classification represents the severity of all grades of complications after colectomy using cost of care modeling. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a comprehensive cancer center. PATIENTS: Consecutive patients (N = 1807) undergoing elective colon or rectal resections without a stoma performed at Memorial Sloan Kettering Cancer Center between 2009 and 2014 who were followed up for ≥90 days, were not transferred to other hospitals, and did not receive intraperitoneal chemotherapy were included in the study. MAIN OUTCOME MEASURES: Complication severity was measured by the highest-grade complication per patient and attributable outpatient and inpatient costs. Associations were evaluated between patient complication grade and cost during 3 time periods: the 90 days after surgery, index admission, and postdischarge (<90 d). RESULTS: Of the 1807 patients (median age = 62 y), 779 (43%) had a complication; 80% of these patients had only grade 1 or 2 complications. Increasing patient complication grade correlated with 90-day cost, driven by inpatient cost differences (p < 0.001). For grade 1 and 2 patients, most costs were incurred after discharge and were the same between these grade categories. Among patients with a single complication (52%), there was no difference in index hospitalization, postdischarge, or total 90-day costs between grade 1 and 2 categories. LIMITATIONS: The study was limited by its retrospective design and generalizability. CONCLUSIONS: The Clavien-Dindo classification correlates well with 90-day costs, driven largely by inpatient resource use. Clavien-Dindo does not discriminate well among patients with low-grade complications in terms of their substantial postdischarge costs. These patients represent 80% of patients with a complication after colectomy. Examining the long-term burden associated with complications can help refine the Clavien-Dindo classification for use in colectomy studies. See Video Abstract at http://links.lww.com/DCR/B521. EVALUACIN DE LA VALIDEZ DE LA CLASIFICACIN DE CLAVIENDINDO EN ESTUDIOS DE COLECTOMA ANLISIS DEL COSTO DE LA ATENCIN EN DAS: ANTECEDENTES:La clasificación de Clavien-Dindo es utilizada ampliamante para conocer la morbilidad posoperatoria, pero puede subestimar la gravedad de las complicaciones de la colectomía.OBJETIVO:Evaluar que tan bien representa la clasificación de Clavien-Dindo la gravedad de todos los grados de complicaciones después de la colectomía utilizando un modelo de costo de la atención.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Centro oncológico integral.PACIENTES:Pacientes consecutivos (n = 1807) sometidos a resecciones electivas de colon o recto sin estoma realizadas en el Memorial Sloan Kettering Cancer Center entre 2009 y 2014 que fueron seguidos durante ≥ 90 días, no fueron transferidos a otros hospitales y no recibieron quimioterapia intraperitoneal.PRINCIPALES MEDIDAS DE VALORACION:Gravedad de la complicación medida por la complicación de mayor grado por paciente y los costos atribuibles para pacientes ambulatorios y hospitalizados. Se evaluó la asociación entre el grado de complicación del paciente y el costo durante 3 períodos de tiempo: posterior a la cirugía (hasta 90 días), a su ingreso y posterior al egreso (hasta 90 días).RESULTADOS:De los 1807 pacientes (mediana de edad de 62 años), 779 (43%) tuvieron una complicación; El 80% de estos pacientes tuvieron solo complicaciones de grado 1 o 2. El aumento del grado de complicación del paciente se correlacionó con el costo a 90 días, impulsado por las diferencias en el costo de los pacientes hospitalizados (p <0,001). Para los pacientes de grado 1 y 2, la mayoría de los costos se incurrieron después del alta y fueron los mismos entre ambas categorías. Entre los pacientes con una sola complicación (52%), no hubo diferencia en el índice de hospitalización, posterior al alta o en el costo total de 90 días entre las categorías de grado 1 y 2.LIMITACIONES:Diseño retrospectivo, generalizabilidad.CONCLUSIONES:La clasificación de Clavien-Dindo se correlaciona bien con los costos a 90 días, impulsados en gran parte por la utilización de recursos de pacientes hospitalizados. Clavien-Dindo no discrimina entre los pacientes con complicaciones de bajo grado en términos de sus costos sustanciales posterior al alta. Estos pacientes representan el 80% de los pacientes aquellos con una complicación tras la colectomía. Examinar la carga a largo plazo asociada a las complicaciones puede ayudar a mejorar la clasificación de Clavien-Dindo para su uso en estudios de colectomía. Consulte Video Resumen en http://links.lww.com/DCR/B521.

Anorectal Mucosal Melanoma in the Era of Immune Checkpoint Inhibition: Should We Change Our Surgical Management Paradigm?

BACKGROUND: The advent of immune checkpoint inhibition therapy has dramatically improved survival in patients with skin melanoma. Survival outcomes after resection of anorectal melanoma treated with immune checkpoint inhibition have not been reported. OBJECTIVE: This study aimed to compare survival outcomes following surgical resection of anorectal melanoma between patients who received immune checkpoint inhibition and patients who did not. DESIGN: This study is a retrospective analysis of data from a prospectively maintained database. SETTING: This study was conducted at a comprehensive cancer center. PATIENTS: Patients who underwent surgery for anorectal melanoma between 2006 and 2017 were included. They were stratified according to the use of immune checkpoint inhibition. MAIN OUTCOME MEASURES: The primary outcomes measured were overall and disease-specific survival. RESULTS: Of the 47 patients included in the analysis, 29 (62%) received immune checkpoint inhibition therapy. Twenty-two (76%) of the 29 patients received immune checkpoint inhibition after detection of metastasis or disease progression rather than in the neoadjuvant or adjuvant setting. Overall survival did not differ significantly between patients who received immune checkpoint inhibition therapy and patients who did not (median, 52 and 20 months; 5-year rate, 41% vs 35%; p = 0.25). Disease-specific survival also did not differ significantly. Our analysis did not identify any clinical or pathological features associated with response to immune checkpoint inhibition therapy or with survival. LIMITATIONS: This study was limited by its relatively small sample and retrospective design and by the heterogeneous treatment regimen in the immune checkpoint inhibition group. CONCLUSIONS: Immune checkpoint inhibition therapy by itself does not appear to improve survival in patients who undergo resection or excision of anorectal melanoma. Combinations of immune checkpoint inhibition with other therapeutic modalities warrant further investigation. See Video Abstract at http://links.lww.com/DCR/B499. MELANOMA DE LA MUCOSA ANORRECTAL EN LA ERA DE LOS INHIBIDORES DEL PUNTO DE CONTROL INMUNOLÓGICO: ¿DEBEMOS DE CAMBIAR NUESTRO PARADIGMA DEL MANEJO QUIRÚRGICO: El advenimiento de la terapia de los inhibidores del punto de control inmunológico, han mejorado dramáticamente la supervivencia en pacientes con melanoma de piel. No se han informado los resultados de supervivencia después de la resección del melanoma anorrectal, tratado con inhibidores del punto de control inmunológico.Comparar los resultados de supervivencia después de la resección quirúrgica de melanoma anorrectal entre pacientes que recibieron y no recibieron inhibidores del punto de control inmunológico.Análisis retrospectivo de una base de datos mantenida prospectivamente.Centro oncológico integral.Pacientes que se sometieron a cirugía por melanoma anorrectal entre 2006 y 2017. Los pacientes fueron estratificados según el uso de inhibidores del punto de control inmunológico.Supervivencia global y específica de la enfermedad.De los 47 pacientes incluidos en el análisis, 29 (62%) recibieron terapia de inhibidores del punto de control inmunológico. Veintidós (76%) de los 29 pacientes recibieron inhibidores del punto de control inmunológico después de la detección de metástasis o progresión de la enfermedad, en vez de administración adyuvante o neoadyuvante. La supervivencia global no varió significativamente entre los pacientes que recibieron o no recibieron terapia de inhibidores del punto de control inmunológico (mediana, 52 y 20 meses, respectivamente; tasa a 5 años, 41% frente a 35%, respectivamente; p = 0,25). La supervivencia específica de la enfermedad tampoco varió significativamente. Nuestro análisis no identificó ninguna característica clínica o patológica, asociada con la respuesta a la terapia de inhibidores del punto de control inmunológico o con la supervivencia.Muestra relativamente pequeña y diseño retrospectivo. Régimen de tratamiento heterogéneo en el grupo de inhibidores del punto de control inmunológico.La terapia por sí sola, de inhibidores del punto de control inmunológico, no parece mejorar la supervivencia en pacientes que se someten a resección o escisión de melanoma anorrectal. Las combinaciones de inhibidores del punto de control inmunológico con otras modalidades terapéuticas, merecen una mayor investigación. Consulte Video Resumen en http://links.lww.com/DCR/B499. (Traducción-Dr. Fidel Ruiz Healy).

Primary Tumor-Related Complications and Salvage Outcomes in Patients with Metastatic Rectal Cancer and an Untreated Primary Tumor.

BACKGROUND: For rectal cancer with unresectable metastases, current practice favors omitting interventions directed at the primary tumor in asymptomatic patients. OBJECTIVE: This study aimed to determine the proportion of patients with primary tumor-related complications, characterize salvage outcomes, and measure survival in patients with metastatic rectal cancer who did not undergo upfront intervention for their primary tumor. DESIGN: This is a retrospective analysis. SETTING: This study was conducted at a comprehensive cancer center. PATIENTS: Patients who presented between January 1, 2008, and December 31, 2015, with synchronous stage IV rectal cancer, an unresected primary tumor, and no prior primary tumor-directed intervention were selected. MAIN OUTCOME MEASURES: The main outcome measured was the rate of primary tumor-related complications in the cohort that did not receive any primary tumor-directed intervention. The Kaplan-Meier method and Cox regression analysis were used to determine whether complications are associated with survival. RESULTS: The cohort comprised 358 patients with a median age of 56 years (22-92). Median follow-up was 26 months (range, 1-93 months). Among the 168 patients (46.9%) who eventually underwent elective resection of the primary tumor, the surgery was performed with curative intent in 66 patients (18.4%) and preemptive intent in 102 patients (28.5%). Of the 190 patients who did not undergo an upfront or elective intervention for the primary tumor, 68 (35.8%) experienced complications. Nonsurgical intervention for complications was attempted in 34 patients with an overall success rate of 61.8% (21/34). Surgical intervention was performed in 47 patients (including 13 patients for whom nonsurgical intervention failed): diversion in 26 patients and resection in 21 patients. Of those 47 patients, 42 (89.4%) ended up with a colostomy or ileostomy. LIMITATIONS: This study was conducted at a single center. CONCLUSION: A significant proportion of patients with metastatic rectal cancer and untreated primary tumor experience primary tumor-related complications. These patients should be followed closely, and preemptive intervention (resection, diversion, or radiation) should be considered if the primary tumor progresses despite systemic therapy. See Video Abstract at http://links.lww.com/DCR/B400. COMPLICACIONES RELACIONADAS CON EL TUMOR PRIMARIO Y RESULTADOS DE RESCATE EN PACIENTES CON CÁNCER DE RECTO METASTÁSICO Y UN TUMOR PRIMARIO NO TRATADO: Para el cáncer de recto con metástasis no resecables, la práctica actual favorece la omisión de las intervenciones dirigidas al tumor primario en pacientes asintomáticos.Determinar la proporción de pacientes con complicaciones relacionadas con el tumor primario, caracterizar los resultados de rescate y medir la supervivencia en pacientes con cáncer rectal metastásico que no se sometieron a una intervención inicial para su tumor primario.Análisis retrospectivo.Centro oncológico integral.Pacientes que se presentaron entre el 1 de enero de 2008 y el 31 de diciembre de 2015 con cáncer de recto en estadio IV sincrónico, un tumor primario no resecado y sin intervención previa dirigida al tumor primario.Tasa de complicaciones relacionadas con el tumor primario en la cohorte que no recibió ninguna intervención dirigida al tumor primario. Se utilizó el método de Kaplan-Meier y el análisis de regresión de Cox para determinar si las complicaciones están asociadas con la supervivencia.La cohorte estuvo compuesta por 358 pacientes con una mediana de edad de 56 años (22-92). La mediana de seguimiento fue de 26 meses (rango, 1 a 93 meses). Entre los 168 pacientes (46,9%) que finalmente se sometieron a resección electiva del tumor primario, la cirugía se realizó con intención curativa en 66 pacientes (18,4%) y con intención preventiva en 102 pacientes (28,5%). De los 190 pacientes que no se sometieron a una intervención inicial o electiva para el tumor primario, 68 (35,8%) experimentaron complicaciones. Se intentó una intervención no quirúrgica para las complicaciones en 34 pacientes con una tasa de éxito global del 61,8% (21 de 34). La intervención quirúrgica se realizó en 47 pacientes (incluidos 13 pacientes en los que falló la intervención no quirúrgica): derivación en 26 pacientes y resección en 21 pacientes. De esos 47 pacientes, 42 (89,4%) terminaron con una colostomía o ileostomía.Único centro.Una proporción significativa de pacientes con cáncer de recto metastásico y primario no tratado experimentan complicaciones relacionadas con el tumor primario. Se debe hacer un seguimiento estrecho de estos pacientes y considerar la posibilidad de una intervención preventiva (resección, derivación o radiación) si el tumor primario progresa a pesar de la terapia sistémica. Consulte Video Resumen en http://links.lww.com/DCR/B400.