Juliana Rodriguez

Sentinel lymph node assessment in patients with atypical endometrial hyperplasia: a systematic review and meta-analysis

This systematic review and meta-analysis aimed to assess the rate of sentinel lymph node (SLN) metastases in patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia and endometrial cancer in hysterectomy specimens. A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and the protocol was registered in PROSPERO (CRD42023416769). MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from inception until April 2023. The inclusion criteria were patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia undergoing hysterectomy who did or did not undergo SLN assessment. Four studies met the inclusion criteria. All studies were non-randomized studies with a total of 10 217 patients, 1044 in the SLN group and 9173 in the non-nodal assessment group. The unilateral and bilateral detection rate was 89% (I The rate of SLN metastases in patients with pre-operative atypical hyperplasia/endometrial intra-epithelial neoplasia is less than 2%, suggesting that routine SLN evaluation may not be necessary in this population.

Management of invasive cervical carcinoma in three oncology centers in Latin America: A historical cohort study

Abstract Objective To describe clinical and sociodemographic characteristics of patients with invasive cervical cancer treated at three oncology centers in Latin America, as well as their risk factors, and management based on the FIGO stage 2009. Methods This is a descriptive historical cohort study of patients with invasive cervical cancer recruited between January 2010 and June 2016. The study describes demographic characteristics, risk factors, treatments, and oncological outcomes at 1 and 5 years. Results A total of 717 patients were included: 433 (60.39%) from INC Colombia, 174 (24.26%) from INCAN Mexico, and 110 (15.34%) from INEN Peru. Most patients were at FIGO Stage 2009 IIB 213 (29.70%), and the most common histologic subtype was squamous cell carcinoma 550 (76.71%). Concurrent chemo‐radiotherapy was the most frequent approach 334 (46.48%), followed by surgical treatment 261 (36.40%) patients. Regarding oncological outcomes, the 5‐year disease‐free survival (DFS) for all patients was 76.72% (95% CI: 73.34%–80.18%), with worse outcomes observed for Stages III and IV compared to early stages. The 5‐year overall survival (OS) for the general group was 83.76% (95% CI: 81.00%–86.73%), with statistically significant differences showing better outcomes for Stage I, with an OS of 94.52% (95% CI: 91.68–97.44). Conclusion In this descriptive historical cohort, most patients received treatment according to their clinical stage. Survival rates, both overall and disease‐free, were better for early‐stage disease compared to advanced stages.

Accuracy of pre-operative tumor size assessment compared to final pathology and frequency of adjuvant treatment in patients with FIGO 2018 stage IB2 cervical cancer

The primary aim of our study was to compare tumor size assessment by pre-operative evaluation (physical examination and/or imaging) with tumor size on final pathology. As a secondary outcome, we evaluated the rate of adjuvant treatment in patients who underwent radical hysterectomy whose tumor size was ≥3 cm on final pathology. Patient details were collected from three separate databases: the University of Texas MD Anderson Cancer Center Radical Hysterectomy Database, the SUCCOR Study Group Database, and the Multi-institutional Database LATAM (encompassing Latin America and Europe). Patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 cervical cancer on pre-operative evaluation (physical examination or imaging) who underwent radical hysterectomy with a therapeutic intent were included. Any histological subtype, any tumor grade, and pre-operative evaluation with clinical evaluation and/or imaging (ultrasound, MRI, CT, or PET/CT) was considered. A total of 675 patients met eligibility criteria (SUCCOR=350, LATAM=250, MD Anderson=75). The median age was 46 years (range 22-82) and the median body mass index was 25.6 kg/m Our study showed that there is a high concordance between tumor size assessment by physical examination and MRI, as well as estimates of measurement by MRI and final pathology. In addition, we noted that the majority of patients with FIGO 2018 stage IB2 received adjuvant therapy after radical hysterectomy.

Complications of HIPEC for ovarian cancer surgery: evaluation over two time periods

Cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) is being explored in the upfront, interval, and recurrent setting in patients with ovarian cancer. The objective of this systematic review was to assess the rate of complications associated with HIPEC in epithelial ovarian cancer surgery over two time periods. This study was registered in PROSPERO (CRD42022328928). A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Ovid/Medline, Ovid/Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials were searched from January 2004 to April 2022. We included studies reporting on patients with advanced primary or recurrent epithelial ovarian cancer who underwent cytoreductive surgery and HIPEC. We evaluated two different time periods: 2004-2013 and 2014-2022. A random-effects meta-analysis was used to produce an overall summary. Subgroup analyses were planned according to recruited period for each specific complication type. Heterogeneity was assessed using the I A total of 4928 patients were included from 69 studies for this systematic review; 19 published from 2004-2013, and 50 published from 2014-2022. No significant differences were found between the two time periods in terms of blood transfusions (33% vs 51%; p=0.46; I Our review showed that overall complications have not changed over time for patients undergoing HIPEC in the setting of primary or recurrent ovarian cancer. There was no decrease in the rates of ICU admissions, reoperations, or deaths.

Oncological and obstetrical outcomes after neo-adjuvant chemotherapy followed by fertility-sparing surgery in patients with cervical cancer ≥2 cm

There is significant debate between up-front radical trachelectomy versus neo-adjuvant chemotherapy before fertility-sparing surgery in patients with tumors ≥2 cm. The aim of this study was to report on the oncological and obstetrical outcome of neo-adjuvant chemotherapy followed by fertility-sparing surgery, in patients diagnosed with cervical cancer ≥2 cm. This was a retrospective review of patients diagnosed with cervical cancer measuring ≥2 cm to ≤6 cm, who were scheduled to undergo neo-adjuvant chemotherapy before fertility-sparing surgery, at six institutions from four Latin American countries between February 2009 and February 2019. Data collected included: age, International Federation of Gynecology and Obstetrics (FIGO) 2009 stage, histology, tumor size, pre-treatment imaging work-up, chemotherapy agents and number of cycles, toxicity, clinical and imaging response rate, type of fertility-sparing surgery, pathology results, timing of lymphadenectomy, follow-up time, and obstetrical and oncological outcomes. A total of 25 patients were included, with a median age of 27 years (range 20-37): 17 patients had stage IB1, 7 had stage IB2 cervical cancer, and 1 patient had stage IIA1 (FIGO 2009); 23 patients had squamous cell carcinoma and 2 patients had adenocarcinoma. The median number of chemotherapy cycles was 3 (range 3-6) and no toxicity grade 3-4 was reported. Lymphadenectomy was performed before chemotherapy in 6 (24%) patients. After neo-adjuvant chemotherapy 20 patients were scheduled for radical trachelectomy (11 abdominal and 9 laparoscopic) and 5 patients for conization. After surgery, no residual disease was found in 11 patients (44%). Fertility was preserved in 23 patients (92%) and 10 patients became pregnant (43.5%). After a median follow-up time of 47 months (13-133), 3 patients had recurrent disease (3/23=13%), 2 were alive without disease, and 1 patient had disease at last contact. Neo-adjuvant chemotherapy followed by fertility-sparing surgery is feasible in well selected patients with cervical tumors ≥2 cm. Future studies should focus on the timing of lymphadenectomy and type of cervical surgery.

Incidence of metastasis in circumflex iliac nodes in patients with cervical cancer: a systematic review

The circumflex iliac nodes distal to the external iliac nodes are frequently removed when bilateral pelvic lymphadenectomy is performed in patients with cervical cancer. The objective of this systematic review was to assess the incidence of metastasis in the circumflex iliac nodes in patients with cervical cancer. PubMed/Medline, ClinicalTrials, Embase, Cochrane Central Register of Controlled Trials, Scopus, and Ovid databases were searched from inception to May 2021. We included articles published in English language reporting all types of studies, except for case reports and commentaries. Abstracts and unpublished studies were excluded. The inclusion criteria were diagnosis of cervical cancer, FIGO 2009 stages IA-IIB, squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma, and primary surgery including pelvic lymph node dissection. A total of 3037 articles were identified. Overall, 1165 eligible patients from four studies were included in the analysis. A total of 696 (59.7%) patients had early-stage disease (FIGO 2009 stages IA, IB1, IIA1). The median number of extracted circumflex iliac nodes, which was reported in two studies, was one (range not reported) and three (range 1-13). The positive lymph node rate for the entire population and circumflex iliac node involvement were 26.9% and 3.1%, respectively. Isolated metastases were reported for 904 patients (three studies) and in one patient nodal spread was detected (0.11%). The rate of isolated metastases in circumflex iliac nodes is small and excision of these lymph nodes as part of routine lymphadenectomy should be avoided.

Neoadjuvant chemotherapy in pregnant patients with cervical cancer: a Latin-American multicenter study

To describe oncologic and obstetric outcomes in patients diagnosed with cervical cancer during pregnancy who had a successful delivery after neoadjuvant chemotherapy. A multicenter retrospective review was conducted in 12 institutions from six Latin American countries, between January 2007 and December 2018. Data collected included clinical characteristics, neoadjuvant chemotherapy agents, treatment, obstetric and oncologic outcomes. Thirty-three patients were included. Median age was 34 years (range 31-36). Twenty (60.6%) women were diagnosed at early stage (IB), and 13 (39.4%) with locally advanced stage (IIA-IIIB) according to FIGO 2009 classification. Carboplatin and paclitaxel was the most frequent combination used (60.6%). Partial and complete response rates were 27.3% and 9.1%, respectively. Median gestational age at delivery was 35 weeks (range 34-36). All patients had live births delivered by cesarean section. Obstetric pathology: pre-term labor, placenta percreta or intra-uterine growth restriction, was documented in seven patients (21.2%). Two (6.1%) neonates had low birth weight. Definitive treatment was primary chemo-radiation in 19 (57.6%) patients, radical hysterectomy in 11 (33.3%), abandoned radical hysterectomy with para-aortic lymphadenectomy and ovarian transposition in 1 patient (3.0%), and no further treatment in 2 (6.1%) patients. After a median follow-up of 16.3 months (range 2.0-36.9), 8 (26.7%) patients had recurrent disease. Of these, four (13.3%) died due to disease. Neoadjuvant chemotherapy may be offered to patients wishing to preserve an ongoing pregnancy in order to achieve fetal maturity. Long-term consequences of chemotherapy in the child are yet to be determined.

Neoadjuvant chemotherapy prior to fertility-sparing surgery in cervical tumors larger than 2 cm: a systematic review on fertility and oncologic outcomes

Management of cervical cancer tumors >2 cm has been a subject of controversy, with management often considered as either up-front radical trachelectomy or neoadjuvant chemotherapy before fertility-sparing surgery. A systematic literature review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) checklist. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO). We searched Medline through PubMed, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, and OVID between January 1985 and December 2020. Eligibility criteria for selecting studies were English language, randomized controlled trials, and observational studies including information on fertility and oncologic outcomes. All titles were managed in EndNote X7. Risk of bias was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklist for observational studies. Twenty-three studies with 205 patients who received neoadjuvant chemotherapy were included. The majority of patients (92.2%, n=189) had stage IB FIGO 2009 cervical cancer. The preferred regimen used was cisplatin in combination with paclitaxel or ifosfamide (80%, n=164). One hundred and eighty patients (87.8%) underwent fertility-sparing surgery; radical vaginal trachelectomy, abdominal trachelectomy, conization, and simple trachelectomy were performed in 62 (34.4%), 49 (27.2%), 34 (18.9%), and 26 (14.4%) women, respectively. In nine patients (5%) the type of procedure was not specified. The follow-up time reported in all studies ranged between 6 and 69 months. In 112 women who sought a pregnancy after surgery, 84.8% (n=95) achieved a gestation.The global recurrence and death rates were 12.8% and 2.8%, respectively. Neoadjuvant chemotherapy followed by fertility-sparing surgery is a promising strategy that might allow fertility preservation in highly selected patients with cervical cancer with tumors >2 cm while providing acceptable oncologic outcomes. Results of prospective studies are required to validate its oncological safety. PROSPERO CRD42020203789.

Oncological outcomes of laparoscopic radical hysterectomy versus radical abdominal hysterectomy in patients with early-stage cervical cancer: a multicenter analysis

Recent evidence has shown adverse oncological outcomes when minimally invasive surgery is used in early-stage cervical cancer. The objective of this study was to compare disease-free survival in patients that had undergone radical hysterectomy and pelvic lymphadenectomy, either by laparoscopy or laparotomy. We performed a multicenter, retrospective cohort study of patients with cervical cancer stage IA1 with lymph-vascular invasion, IA2, and IB1 (FIGO 2009 classification), between January 1, 2006 to December 31, 2017, at seven cancer centers from six countries. We included squamous, adenocarcinoma, and adenosquamous histologies. We used an inverse probability of treatment weighting based on propensity score to construct a weighted cohort of women, including predictor variables selected a priori with the possibility of confounding the relationship between the surgical approach and survival. We estimated the HR for all-cause mortality after radical hysterectomy with weighted Cox proportional hazard models. A total of 1379 patients were included in the final analysis, with 681 (49.4%) operated by laparoscopy and 698 (50.6%) by laparotomy. There were no differences regarding the surgical approach in the rates of positive vaginal margins, deep stromal invasion, and lymphovascular space invasion. Median follow-up was 52.1 months (range, 0.8-201.2) in the laparoscopic group and 52.6 months (range, 0.4-166.6) in the laparotomy group. Women who underwent laparoscopic radical hysterectomy had a lower rate of disease-free survival compared with the laparotomy group (4-year rate, 88.7% vs 93.0%; HR for recurrence or death from cervical cancer 1.64; 95% CI 1.09-2.46; P=0.02). In sensitivity analyzes, after adjustment for adjuvant treatment, radical hysterectomy by laparoscopy compared with laparotomy was associated with increased hazards of recurrence or death from cervical cancer (HR 1.7; 95% CI 1.13 to 2.57; P=0.01) and death for any cause (HR 2.14; 95% CI 1.05-4.37; P=0.03). In this retrospective multicenter study, laparoscopy was associated with worse disease-free survival, compared to laparotomy.

Adjuvant treatment after radical surgery for cervical cancer with intermediate risk factors: is it time for an update?

Cervical cancer is the fourth most common cancer in women worldwide. The preferred treatment for early stage cervical cancer is radical hysterectomy with pelvic lymph node assessment, and adjuvant therapy is suggested according to histopathological risk factors. A landmark study was published in 1999 that established 'intermediate risk' criteria for relapse, showing a benefit in recurrence free rate in patients that received pelvic radiotherapy. Furthermore, in the presence of parametrial, nodal, or vaginal margin involvement, another key study found that the addition of concurrent cisplatin based chemotherapy to radiation therapy improved progression free and overall survival for 'high risk' early cervical cancer. With the advancement in treatment modalities in surgery and radiotherapy, and the improved identification of prognostic histopathological factors, several authors have reconsidered the role of adjuvant therapy after radical hysterectomy in the presence of intermediate risk criteria. Here we review the literature on the evolution of adjuvant therapy for intermediate risk factors.

Fertility-sparing surgery after neo-adjuvant chemotherapy in women with cervical cancer larger than 4 cm: a systematic review

The objective of this systematic review was to assess the oncologic and fertility outcomes of patients with cervix-confined cancer >4 cm who underwent neo-adjuvant chemotherapy followed by fertility-sparing surgery. This study was registered in PROSPERO (registration number CRD42021254816). PubMed/MEDLINE, ClinicalTrials, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, and OVID databases were searched from inception to July 2021. The included patients were those with cancer confined to the cervix and tumor diameter >4 cm (International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB3) with squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma who underwent intra-venous neo-adjuvant chemotherapy followed by successful fertility-sparing surgery. The initial search identified 2990 articles. A total of 40 patients from 11 studies had attempted fertility preservation surgery (conization, simple or radical trachelectomy) and in 26 patients (65%) it was successful. All patients received platinum-based chemotherapy. A complete pathological response occurred in 56% of patients and two patients (7.7%) had a recurrence. The 4.5-year disease-free survival was 92.3% and the 4.5-year overall survival rate was 100%. Of six patients who tried to conceive, four (67%) achieved at least one pregnancy and three of the five pregnancies (60%) were pre-term deliveries (all after radical trachelectomy). All patients with recurrence received cisplatin and ifosfamide instead of cisplatin and paclitaxel, underwent non-radical surgery, and had residual disease in the final specimen. Evidence for fertility-sparing surgery after neo-adjuvant chemotherapy in patients with cervical cancer and tumors >4 cm is limited, and this approach should be considered as an experimental intervention. As the use of non-radical surgery could be a risk factor, if neo-adjuvant chemotherapy is used, patients should undergo fertility-sparing radical surgery.

Definitive pelvic radiotherapy for patients with newly diagnosed stage IVB cervical cancer: a systematic review

The objective of this systematic review was to assess the oncologic outcomes of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IVB cervical cancer receiving definitive pelvic radiotherapy compared with systemic chemotherapy (with or without palliative pelvic radiotherapy). This study was registered in PROSPERO (registration number CRD42022333433). A systematic literature review was conducted following the MOOSE checklist. MEDLINE (through Ovid), Embase, and Cochrane Central Register of Controlled Trials were searched from inception until August 2022. The inclusion criteria were patients with metastatic FIGO 2018 stage IVB cervical cancer, a histologic subtype of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma that received definitive pelvic radiotherapy (≥45 Gy) as part of management compared with systemic chemotherapy with or without palliative (30 Gy) pelvic radiotherapy. Randomized controlled trials and observational studies with two arms of comparison were considered. The search identified 4653 articles; 26 studies were considered potentially eligible after removing duplicates, and 8 met the selection criteria. In total, 2424 patients were included. There were 1357 and 1067 patients in the definitive radiotherapy and chemotherapy groups, respectively. All included studies were retrospective cohort studies, and two were database population studies. The median overall survival reported in seven studies for the definitive radiotherapy arm versus systemic chemotherapy groups were 63.7 months versus 18.4 months (p<0.01), 14 months versus 16 months (p value not reported), 17.6 months versus 10.6 months (p<0.01), 32 months versus 24 months (p<0.01), 17.3 months versus 10 months (p<0.01), and 41.6 months versus 17.6 months (p<0.01), and not reached versus 19 months (p=0.13) respectively, favoring the groups that received definitive pelvic radiotherapy. The high clinical heterogeneity precluded the performance of meta-analysis, and all studies were at serious risk of bias. Definitive pelvic radiotherapy as part of treatment in patients with stage IVB cervical cancer may improve oncologic outcomes compared with systemic chemotherapy (with or without palliative radiotherapy); however, this is based on low-quality data. Prospective evaluation would be ideal before the adoption of this intervention in standard clinical practice.

Can international standards in ovarian cancer treatment be attained by low- and middle-income countries?

Consenso de expertos basado en la evidencia: perfilamiento y manejo del carcinoma epitelial de ovario de alto grado avanzado

Introducción y objetivo: el abordaje de pacientes con cáncer epitelial de ovario (CEO) de alto grado avanzado o metastásico ha ido evolucionando a través del tiempo con el advenimiento de nuevas terapias y estrategias multimodales. El objetivo de este consenso de expertos es generar recomendaciones nacionales para el perfilamiento y manejo del CEO de alto grado avanzado o metastásico, definido como estadios III y IV de la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) al momento del diagnóstico, a partir de la revisión de la literatura que incluyó guías de práctica clínica (GPC) internacionales basadas en la evidencia. Materiales y métodos: once panelistas (oncólogos y ginecólogos oncólogos) respondieron ocho preguntas sobre el perfilamiento y manejo del carcinoma epitelial de ovario avanzado o metastásico. Los panelistas fueron escogidos por su perfil académico e influencia en instituciones de salud nacionales. Para el desarrollo del consenso se utilizaron los lineamientos de la “Conferencia de consenso de procedimientos operativos estandarizados de ESMO”. Se definió que el nivel de acuerdo para aceptar una recomendación debía ser ≥ 80%. El documento fue revisado por pares. Resultados: Se hacen 8 recomendaciones generales, presentadas en cinco dominios; algunas de ellas se subdividen en recomendaciones específicas. Tratamiento inicial Recomendación 1 1.1. Como terapia inicial de elección para pacientes con CEO de alto grado o metastásico se sugiere la cirugía de citorreducción primaria (Cpr) completa que, idealmente, debe realizarse en centros con experiencia, seguida de terapia adyuvante. 1.2. Se sugiere quimioterapia neoadyuvante seguida de cirugía de citorreducción de intervalo (Cint) en quienes sea improbable alcanzar una citorreducción completa en la Cpr, bien sea por enfermedad metastásica no resecable o que presenten criterios de irresecabilidad (imagenológicos, laparoscópicos o por laparotomía) que hayan sido definidos por un ginecólogo oncólogo. También en pacientes con un pobre estado funcional y comorbilidades de acuerdo con el criterio del equipo multidisciplinario (oncología clínica, ginecología oncológica, radiología, etc.). Recomendación 2. En pacientes con CEO de alto grado, en estadio III localmente avanzado o metastásico, que recibieron quimioterapia neoadyuvante y alcanzaron respuesta completa o parcial (citorreducción con residuo tumoral &lt; 2,5 mm), se podría evaluar el uso de la quimioterapia intraperitoneal hipertérmica (Hyperthermic IntraPeritoneal Chemotherapy - HIPEC) como alternativa a la quimioterapia IV adyuvante estándar basada en platinos durante la Cint, previa discusión en junta multidisciplinaria, en un centro de experiencia en este tipo de pacientes. Uso de pruebas genéticas Recomendación 3. Al momento del diagnóstico, se sugiere ofrecer testeo molecular genético a toda paciente con CEO de alto grado avanzado o metastásico, independientemente de la historia familiar. Recomendación 4. Se sugiere ofrecer asesoramiento genético, por parte de personal calificado, a toda paciente con CEO de alto grado avanzado o metastásico a quien se le ordene un testeo genético. Recomendación 5. Se sugiere que a toda paciente con CEO de alto grado avanzado o metastásico se le realice panel germinal que incluya los genes de susceptibilidad al cáncer de mama 1/2 (BRCA 1/2) y los otros genes de susceptibilidad de acuerdo con los protocolos institucionales y la disponibilidad de paneles de testeo genético; si es negativo entonces se debería realizar testeo somático que incluya el estatus de deficiencia de la recombinación homóloga (homologous recombination deficiency - HRD), independientemente de la historia familiar. Terapia adyuvante Recomendación 6 6.1. Se sugiere que a toda paciente con CEO estadios III/IV avanzado o metastásico, con estatus de desempeño (performance score care - PSC) de 0-2 se le administre como tratamiento estándar quimioterapia intravenosa (IV) adyuvante dentro de las seis semanas posteriores a la Cpr. Se sugiere administrar paclitaxel/carboplatino. 6.2. Se sugiere utilizar quimioterapia estándar basada en platino más bevacizumab como adyuvancia en pacientes con enfermedad de alto riesgo (CEO estadios IV o III con citorreducción tumoral subóptima), continuando con bevacizumab como mantenimiento. No se recomienda el uso de bevacizumab como terapia de mantenimiento si no se incluyó en la primera línea de tratamiento. Se sugiere seguir los esquemas de los estudios Gynecologic Oncology Group Study (GOG-0218) e International Collaborative Ovarian Neoplasm (ICON7). 6.3. Se sugiere la quimioterapia combinada IV/intraperitoneal (IP) solo para pacientes seleccionadas, con una citorreducción óptima (lesiones residuales &lt; 1 cm), en especial aquellas sin enfermedad residual (R0) y que sean evaluadas en junta multidisciplinaria. La quimioterapia combinada IV/IP no se considera como tratamiento estándar. 6.4. 6.4.1. Se sugiere utilizar inhibidores de poli(ADP-ribosa) polimerasa (PARP) tales como olaparib o niraparib como mantenimiento después de recibir una primera línea de quimioterapia en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino y obtuvieron respuesta completa/respuesta parcial (RC/RP). 6.4.2. Se sugiere utilizar olaparib solo o en combinación con bevacizumab o niraparib en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. 6.4.3. Se sugiere utilizar niraparib en pacientes con CEO estadio III/IV BRCA1/2 negativo o desconocido que recibieron quimioterapia basada en platino y obtuvieron RC/RP. 6.4.4. Se sugiere utilizar bevacizumab u olaparib más bevacizumab en pacientes con CEO estadios III/IV BRCA1/2 negativo o desconocido (HRD positivo) que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. Tratamiento de la recaída de la enfermedad Recomendación 7. Se sugiere la realización de la cirugía de citorreducción secundaria (Csec), seguida de quimioterapia, a pacientes seleccionadas con CEO de alto grado avanzado o metastásico en primera recaída, platino-sensibles (intervalo libre de platinos ≥ 6 meses), puntuación Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) positiva o Integrate model (I-Model) positivo (&lt; 4,7), y con una potencial resección a R0, en centros con acceso a soporte quirúrgico y posoperatorio óptimo. Nota: el intervalo libre de tratamiento con platinos y la puntuación AGO solo se han desarrollado como predictores positivos de resección completa y no para excluir a las pacientes de la cirugía. Recomendación 8 8.1. Para pacientes con CEO de alto grado avanzado o metastásico en recaída platino-sensibles se sugiere: Quimioterapia combinada basada en platino: carboplatino/doxorrubicina liposomal o carboplatino/paclitaxel o carboplatino/ nab-paclitaxel o carboplatino/docetaxel o carboplatino/gemcitabina, por seis ciclos. Si no se tolera la terapia combinada, dar carboplatino o cisplatino solo. Quimioterapia combinada: carboplatino/gemcitabina o carboplatino/paclitaxel o carboplatino/doxorubicina liposomal, más bevacizumab, seguida de bevacizumab como mantenimiento (hasta progresión o toxicidad). 8.2. Para pacientes con CEO de alto grado avanzado o metastásico en recaída, platino-resistentes, se sugiere: Tratamiento secuencial con quimioterapia, preferiblemente con un agente único que no sea un platino (paclitaxel semanal o doxorrubicina liposomal pegilada o docetaxel o etopósido oral o gemcitabina o trabectidina o topotecan). El paclitaxel semanal o la doxorrubicina liposomal pegilada o el topotecan pueden ser administrados con o sin bevacizumab. Existen otros agentes que se consideran potencialmente act ivos (capecitabina, ciclofosfamida, ifosfamida, irinotecán, oxaliplatino, pemetrexed, vinorelbina, ciclofosfamida), que se podrían recomendar para líneas posteriores. Las pacientes con receptores hormonales positivos que no toleran o no tienen respuesta a los regímenes citotóxicos pueden recibir terapia hormonal con tamoxifeno u otros agentes, incluidos los inhibidores de la aromatasa (anastrozol y letrozol) o acetato de leuprolide o acetato de megestrol. Pacientes con PSC ≥ 3 deberían ser consideradas solo para el mejor cuidado de soporte. 8.3. Terapia de mantenimiento con inhibidores PARP. Para pacientes con CEO de alto grado avanzado o metastásico en recaída estadios III/IV BRCA1/2 (positivo, negativo o desconocido), que hayan recibido dos o más líneas de quimioterapia basada en platino y hayan alcanzado RC/RP, se sugiere utilizar olaparib, niraparib o rucaparib. El niraparib podría ser útil en pacientes BRCA 1/2 +/-/desconocido, al igual que el rucaparib, sin embargo, este último no tiene aún aprobación del ente regulador en Colombia. Conclusiones: se espera que las recomendaciones emitidas en este consenso contribuyan a mejorar la atención clínica, el impacto oncológico y la calidad de vida de estas mujeres.

Consenso colombiano para el diagnóstico molecular del cáncer de endometrio

Objetivos: el programa Cancer Genome Atlas Research (TCGA) desarrolló la clasificación molecular para cáncer endometrial con utilidad pronóstica y terapéutica, la cual ha sido reemplazada por consensos y guías internacionales por la clasificación ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) debido a su alto costo. El objetivo de este artículo es presentar recomendaciones a nivel nacional derivadas de un consenso de expertos que permitan unificar e implementar la clasificación molecular para mujeres con cáncer endometrial, mediante un uso racional de recursos y tecnología. Materiales y métodos: consenso de 36 expertos en oncología clínica, ginecología oncológica, patología y genética con práctica clínica en el territorio nacional. El grupo líder realizó una revisión de la literatura y estructuración de preguntas calificadas de 1 a 9 puntos. Se utilizó la técnica de grupo nominal modificada. Se efectuaron reuniones presenciales con presentaciones magistrales, diálogo deliberativo y votación de cuestionario Google Forms (Google LLC, Mountain View, CA, USA) con análisis y discusión de respuestas. Las respuestas no consensuadas se llevaron a una segunda ronda de votación. Finalmente, se elaboró y revisó el manuscrito final. Resultados: se formularon siete recomendaciones integrando las respuestas de las panelistas basadas en evidencia, pero ajustadas al contexto y a la realidad colombiana. Recomendación 1. Se recomienda realizar la clasificación molecular en todos los carcinomas endometriales utilizando los marcadores de inmunohistoquímica como resultados subrogados del perfil molecular inicialmente propuesto en la clasificación del TCGA. Recomendación 2. Se recomienda la estrategia secuencial de testeo iniciando por los marcadores de inmunohistoquímica (p53, MLH1, MSH 2, MSH6, PMS2) simultáneamente en todas las pacientes, y definir la solicitud del POLE (polimerasa épsilon del DNA) (si se encuentra disponible) de forma diferida de acuerdo con la clasificación de riesgo basado en la pieza quirúrgica. Recomendación 3. Se recomienda que sea el ginecólogo oncólogo quien solicite el POLE (si se encuentra disponible) de acuerdo con el reporte de patología definitivo. Esta prueba se debe solicitar a todos los cánceres endometriales de estadio I-II, excepto los de bajo riesgo (estadio IA endometrioide de bajo grado sin invasión linfovascular p53 normal) y estadio III-IV sin enfermedad residual, sin afectar la solicitud de los marcadores moleculares subrogados por inmunohistoquímica de acuerdo con la histología. El consenso propone que la solicitud del POLE se realice posterior a la inmunohistoquímica y de acuerdo con la clasificación del riesgo según las categorías establecidas por la guía ESGO/ESTRO/ESP del 2020. Recomendación 4. Se recomienda realizar simultáneamente con los otros marcadores de inmunohistoquímica la prueba para receptores hormonales en todas las pacientes con cáncer endometrial y el HER2 en pacientes con p53abn. Recomendación 5. Se recomienda que los marcadores de inmunohistoquímica (p53, MLH1, MSH2, MSH6 y PMS2) se realicen en la biopsia/legrado endometrial inicial cuando la muestra es adecuada y está disponible. En caso de inmunohistoquímica inicial no concluyente, o discrepancias histológicas entre la patología inicial y definitiva, se recomienda repetir el perfil molecular en la patología quirúrgica. Los marcadores de inmunohistoquímica deben reportarse en el informe de patología de acuerdo con las recomendaciones del CAP (College of American Pathologists), independientemente del tipo de muestra. Recomendación 6. Se recomienda realizar estudio de metilación de promotor de MLH1 en pacientes con pérdida de expresión de MLH1 en la inmunohistoquímica, acompañado o no de pérdida de expresión de PMS2. Todas las pacientes con déficit de MMR (mismatch repair), deben ser enviadas a genética para descartar síndrome de Lynch. Recomendación 7. Se recomienda tener en cuenta la clasificación molecular, además de los criterios histopatológicos clásicos para la toma de decisiones de adyuvancia, tal como los incorpora la clasificación de los grupos pronósticos de la guía ESGO/ ESTRO/ESP del 2020. Conclusiones: es necesario implementar la clasificación molecular de cáncer de endometrio en la práctica clínica acorde al contexto colombiano, dado su valor pronóstico y posiblemente predictivo. Esto permitirá la caracterización de la población colombiana para ofrecer tratamientos guiados de manera individualizada. Se trata de un documento académico y no regulatorio.

Pelvic lymph node involvement and risk of recurrence in HPV‐associated endocervical adenocarcinoma stage IA2‐IB1 according to Silva's system in two Colombian cancer centers

AbstractObjectiveTo compare the pelvic lymph node involvement and risk of recurrence in patients with human papillomavirus (HPV)‐associated endocervical adenocarcinoma stage IA2‐IB1 undergoing hysterectomy and/or trachelectomy plus lymphadenectomy, according to Silva's classification system.MethodsA retrospective cohort study was performed in two Colombian cancer centers. The cases were classified according to the Silva classification system. Clinical, surgical, and histopathological variables were evaluated. Recurrence risk was analyzed by patterns A, B, or C. A logistic regression model was performed for tumor recurrence. The Kaplan–Meier method was used to estimate overall survival and disease‐free survival (DFS). A weighted kappa was performed to determine the degree of concordance between pathologists.ResultsA total of 100 patients were identified, 33% pattern A, 29% pattern B, and 38% pattern C. The median follow‐up time was 42.5 months. No evidence of lymph node involvement was found in patients classified as A and B, while in the C pattern was observed in 15.8% (n = 6) of cases (P &lt; 0.01). There were 7% of cases with recurrent disease, of which 71.5% corresponded to type C pattern. Patients with Silva pattern B and C had 1.22‐ and 4.46‐fold increased risk of relapse, respectively, compared with pattern A. The 5‐year DFS values by group were 100%, 96.1%, and 80.3% for patterns A, B, and C, respectively.ConclusionFor patients with early‐stage HPV‐associated endocervical adenocarcinoma, the type C pattern presented more lymph node involvement and risk of recurrence compared to the A and B patterns. The concordance in diagnosis of different Silva's patterns by independents pathologists were good.