Cervical cancer: a new era.

Cervical cancer is a major global health issue, ranking as the fourth most common cancer in women worldwide. Depending on stage, histology, and patient factors, the standard management of cervical cancer is a combination of treatment approaches, including (fertility- or non-fertility-sparing) surgery, radiotherapy, platinum-based chemotherapy, and novel systemic therapies such as bevacizumab, immune checkpoint inhibitors, and antibody-drug conjugates. While ambitious global initiatives seek to eliminate cervical cancer as a public health problem, the management of cervical cancer continues to evolve with major advances in imaging modalities, surgical approaches, identification of histopathological risk factors, radiotherapy techniques, and biomarker-driven personalized therapies. In particular, the introduction of immune checkpoint inhibitors has dramatically altered the treatment of cervical cancer, leading to significant survival benefits in both locally advanced and metastatic/recurrent settings. As the landscape of cervical cancer therapies continues to evolve, the aim of the present review is to provide a comprehensive discussion of the current state and the latest practice-changing updates in cervical cancer.

Value of sentinel node ultrastaging and pathologic techniques in tumoral detection.

PURPOSE OF REVIEW: Sentinel lymph node assessment is an option for patients with clinically early-stage vulvar cancer, endometrial cancer, cervical cancer, and, more recently, ovarian cancer. However, although ultrastaging is mandatory as part of the node evaluation, universally accepted pathology protocols are lacking. This review focuses on the current evidence for the most relevant aspects of sentinel lymph node evaluation, as well as some controversial topics like frozen section or one-step nucleic acid amplification. RECENT FINDINGS: The diagnostic accuracy of sentinel lymph node detection algorithms for patients with gynecologic neoplasms is high. However, the heterogeneity among the published studies and the absence of clear recommendations from most guidelines make it challenging to recommend one protocol over another. The minimum requirement from ultrastaging protocols (regarding the number of levels to be assessed, among others) to get the highest accuracy with a minor cost is unknown. SUMMARY: Sentinel lymph node evaluation is now part of the surgical management for most early-stage gynecologic neoplasms. However, a universally accepted ultrastaging pathology protocol is lacking in literature and clinical practice. This gap requires significant effort from the gynecologic oncology and pathology community to be closed and then to allow advancements in surgical management for early-stage gynecologic tumors to go forward.

Notable surgical trials in gynecologic oncology: a 10-year overview.

In the last decade, we have witnessed important advances in novel therapeutics in the management of gynecologic cancers. These studies have built on the findings from preexisting data and have provided incremental contributions leading to changes that have not only impacted the accuracy of cancer detection and its metastatic components but also led to improvements in oncologic outcomes and quality of life. Key landmark trials have changed the standard of care in cervix, uterine, and ovarian cancer. A number of these have been controversial and have generated significant debate among gynecologic oncologists. The main objective of this review was to provide an overview on each of these trials as a reference for immediate and consolidated access to the study aims, methodology, results, and conclusion.

Adjuvant external beam radiotherapy combined with brachytherapy for intermediate-risk cervical cancer.

OBJECTIVE: Patients with intermediate-risk cervical cancer receive external beam radiotherapy (EBRT) as adjuvant treatment. It is commonly administered with brachytherapy without proven benefits. Therefore, we evaluated the frequency of brachytherapy use, the doses for EBRT administered alone or with brachytherapy, and the overall survival impact of brachytherapy in patients with intermediate-risk, early-stage cervical cancer. METHODS: This retrospective cohort study was performed using data collected from the National Cancer Database. Patients diagnosed with cervical cancer from 2004 to 2019 who underwent a radical hysterectomy and lymph node staging and had disease limited to the cervix but with tumors larger than 4 cm or ranging from 2 to 4 cm with lymphovascular space invasion (LVSI) were included. Patients with distant metastasis or parametrial involvement were excluded. Patients who underwent EBRT alone were compared with those who also received brachytherapy after 2:1 propensity score matching. RESULTS: In total, 1174 patients met the inclusion criteria, and 26.7% of them received brachytherapy. After 2:1 propensity score matching, we included 620 patients in the EBRT group and 312 in the combination treatment group. Patients who received brachytherapy had higher equivalent doses than those only receiving EBRT. Overall survival did not differ between the two groups (hazard ratio (HR) 0.88 (95% confidence interval (CI), 0.62 to 1.23]; p=0.45). After stratification according to tumor histology, LVSI, and surgical approach, brachytherapy was not associated with improved overall survival. However, in patients who did not receive concomitant chemotherapy, the overall survival rate for those receiving EBRT and brachytherapy was significantly higher than that for those receiving EBRT alone (HR, 0.48 (95% CI, 0.27 to 0.86]; p=0.011). CONCLUSION: About one-fourth of the study patients received brachytherapy and EBRT. The variability in the doses and radiotherapy techniques used highlights treatment heterogeneity. Overall survival did not differ for EBRT with and without brachytherapy. However, overall survival was longer for patients who received brachytherapy but did not receive concomitant chemotherapy.

LACC Trial: Final Analysis on Overall Survival Comparing Open Versus Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The aim of this study was to compare overall survival between open and minimally invasive radical hysterectomy with participants followed for 4.5 years. The primary objective was to evaluate whether minimally invasive surgery was noninferior in disease-free survival (DFS) to abdominal radical hysterectomy. Secondary outcomes included overall survival. Sample size was based on DFS of 90% at 4.5 years and 7.2% noninferiority margin for minimally invasive surgery. A total of 631 patients were enrolled: 319 assigned to minimally invasive and 312 to open surgery. Of these, 289 (90.6%) patients underwent minimally invasive surgery and 274 (87.8%) patients open surgery. At 4.5 years, DFS was 85.0% in the minimally invasive group and 96% in the open group (difference of -11.1; 95% CI, -15.8 to -6.3; P = .95 for noninferiority). Minimally invasive surgery was associated with lower rate of DFS compared with open surgery (hazard ratio [HR], 3.91 [95% CI, 2.02 to 7.58]; P < .001). Rate of overall survival at 4.5 years was 90.6% versus 96.2% for the minimally invasive and open surgery groups, respectively (HR for death of any cause = 2.71 [95% CI, 1.32 to 5.59]; P = .007). Given higher recurrence rate and worse overall survival with minimally invasive surgery, an open approach should be standard of care.

Association of reviewer experience with discriminating human-written versus ChatGPT-written abstracts.

OBJECTIVE: To determine if reviewer experience impacts the ability to discriminate between human-written and ChatGPT-written abstracts. METHODS: Thirty reviewers (10 seniors, 10 juniors, and 10 residents) were asked to differentiate between 10 ChatGPT-written and 10 human-written (fabricated) abstracts. For the study, 10 gynecologic oncology abstracts were fabricated by the authors. For each human-written abstract we generated a ChatGPT matching abstract by using the same title and the fabricated results of each of the human generated abstracts. A web-based questionnaire was used to gather demographic data and to record the reviewers' evaluation of the 20 abstracts. Comparative statistics and multivariable regression were used to identify factors associated with a higher correct identification rate. RESULTS: The 30 reviewers discriminated 20 abstracts, giving a total of 600 abstract evaluations. The reviewers were able to correctly identify 300/600 (50%) of the abstracts: 139/300 (46.3%) of the ChatGPT-generated abstracts and 161/300 (53.7%) of the human-written abstracts (p=0.07). Human-written abstracts had a higher rate of correct identification (median (IQR) 56.7% (49.2-64.1%) vs 45.0% (43.2-48.3%), p=0.023). Senior reviewers had a higher correct identification rate (60%) than junior reviewers and residents (45% each; p=0.043 and p=0.002, respectively). In a linear regression model including the experience level of the reviewers, familiarity with artificial intelligence (AI) and the country in which the majority of medical training was achieved (English speaking vs non-English speaking), the experience of the reviewer (ß=10.2 (95% CI 1.8 to 18.7)) and familiarity with AI (ß=7.78 (95% CI 0.6 to 15.0)) were independently associated with the correct identification rate (p=0.019 and p=0.035, respectively). In a correlation analysis the number of publications by the reviewer was positively correlated with the correct identification rate (r28)=0.61, p<0.001. CONCLUSION: A total of 46.3% of abstracts written by ChatGPT were detected by reviewers. The correct identification rate increased with reviewer and publication experience.

De-escalation of surgical radicality for non-fertility preserving management in patients with early-stage cervical cancer: a systematic review.

OBJECTIVE: We sought to evaluate the oncologic outcomes of simple hysterectomy in patients with low-risk early-stage cervical cancer (tumors ≤2 cm with limited stromal invasion). METHODS: This study was registered in PROSPERO (registration number CRD42023433840) following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) checklist. MEDLINE (through Ovid), EmMBASEbase, and Cochrane Central Register of Controlled Trials were searched from inception until June 2023. Randomized controlled trials and observational studies with two arms of comparison (simple hysterectomy with lymph node assessment vs radical hysterectomy with lymph node assessment) in patients with low-risk early-stage cervical cancer were considered. RESULTS: The search identified 1270 articles; eighteen studies were considered potentially eligible after removing duplicates, and four met the selection criteria. Three studies were randomized controlled trials, and the other was a retrospective cohort study. In total, 981 patients were included. There were 485 (49.4%) and 496 (50.6%) patients in the simple hysterectomy and radical hysterectomy groups, respectively. Simple hysterectomy with lymph node assessment was not associated with a higher risk of death at 5 years (RR 0.98, 95% CI: 0.31 to 3.10; I2=0%, two randomized controlled trials, 141 patients, for an absolute risk reduction of zero percentage points [95% CI -9.0 to 9.0]), pelvic recurrence at 3 years (97.5% and 97.8% for simple hysterectomy and radical hysterectomy, respectively, p=0.79), and overall recurrence at 3 years (95 %% and 100% for simple hysterectomy and radical hysterectomy, respectively, p=0.30). CONCLUSION: Simple hysterectomy with lymph node evaluation for low-risk early-stage cervical cancer is not associated with a detrimental effect on oncologic outcomes and has a better morbidity profile.

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.

OBJECTIVE: To 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. METHODS: A 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. RESULTS: A 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 < 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. CONCLUSION: For 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.

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer.

OBJECTIVE: The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. METHODS: A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. RESULTS: Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. CONCLUSION: Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.

Fertility-sparing surgery vs standard surgery for early-stage cervical cancer: difference in 5-year life expectancy by tumor size.

BACKGROUND: Cervical cancer incidence among premenopausal women is rising, and fertility-sparing surgery serves as an important option for this young population. There is a lack of evidence on what tumor size cutoff should be used to define candidacy for fertility-sparing surgery. OBJECTIVE: We sought to describe how the association between fertility-sparing surgery (compared with standard surgery) and life expectancy varies by tumor size among patients with cervical cancers measuring ≤4 cm in largest diameter. Our secondary objective was to quantify the probability of undergoing adjuvant radiotherapy among patients who underwent fertility-sparing surgery as a function of tumor size. STUDY DESIGN: We identified patients in the National Cancer Database aged ≤45 years, diagnosed with stage I cervical cancer with tumors ≤4 cm between 2006 and 2018, who received no preoperative radiation or chemotherapy, and who underwent either fertility-sparing surgery (cone or trachelectomy, either simple or radical) or standard surgery (simple or radical hysterectomy) as their primary treatment. Propensity-score matching was performed to compare patients who underwent fertility-sparing surgery with those who underwent standard surgery. A flexible parametric model was employed to quantify the difference in life expectancy within 5 years of diagnosis (restricted mean survival time) based on tumor size among patients who underwent fertility-sparing and those who underwent standard surgery. In addition, among those who underwent fertility-sparing surgery, a logistic regression model was used to explore the relationship between tumor size and the probability of receiving adjuvant radiation. RESULTS: A total of 11,946 patients met the inclusion criteria of whom 904 (7.6%) underwent fertility-sparing surgery. After propensity-score matching, 897 patients who underwent fertility-sparing surgery were matched 1:1 with those who underwent standard surgery. Although the 5-year life expectancy was similar among patients who had fertility sparing surgery and those who had standard surgery regardless of tumor sizes, the estimates of life-expectancy differences associated with fertility-sparing surgery were more precise among patients with smaller tumors (1-cm tumor: restricted mean survival time difference, -0.10 months; 95% confidence interval, -0.67 to 0.47) than among those with larger tumors (4-cm tumor: restricted mean survival time difference, -0.11 months; 95% confidence interval, -3.79 to 3.57). The probability of receiving adjuvant radiation increased with tumor size, ranging from 5.6% (95% confidence interval, 3.9-7.9) for a 1-cm tumor to 37% (95% confidence interval, 24.3-51.8) for a 4-cm tumor. CONCLUSION: Within 5 years of diagnosis, young patients with stage I cancers measuring ≤4 cm had similar survival outcomes after either fertility-sparing surgery or standard surgery. However, because few patients with tumors >2 cm underwent fertility-sparing surgery, a clinically important survival difference could not be excluded in this population.

Papel de la linfadenectomía paraaórtica inframesentérica durante la histerectomía radical en pacientes con cáncer cervical estadio IB1 en el Instituto Nacional de Cancerología Bogotá, Colombia / Role of inframesenteric para-aortic lymphadenectomy during radical hysterectomy in patients with IB1 cervical cancer in Instituto Nacional de Cancerología Bogota, Colombia

INTRODUCCIÓN: El cáncer cervical es una patología común en países en vías de desarrollo. La histerectomía radical es el estándar de manejo en estadios tempranos sin deseo de fertilidad. La linfadenectomía paraaórtica como parte del tratamiento quirúrgico es controversial. El objetivo de este estudio es determinar la frecuencia de compromiso ganglionar paraaórtico en una serie retrospectiva de pacientes con carcinoma cervical estadio IB1 (clasificación FIGO 2009) llevadas a histerectomía radical mas linfadenectomía pélvica y paraaórtica en el Instituto Nacional de Cancerología durante el periodo de enero 1 de 2009 a marzo 31 de 2017. MÉTODOS: Estudio descriptivo, retrospectivo. Se describieron variables clínicas, operatorias e histopatológicas. Se determinó la frecuencia de compromiso ganglionar a nivel paraaórtico o pélvico, y concurrente. Se realizó análisis univariado en el software estadístico R Project versión 3.6.0. RESULTADOS: Se incluyeron 88 casos. El promedio de edad fue 44,24 ± 9,99 años. La mediana del número de ganglios pélvicos y paraaórticos resecados fue de 23 (6-68) y 4 (1-25), respectivamente. En el 12,5% de las pacientes se observó compromiso tumoral ganglionar pélvico. No se detectó compromiso metastásico de ganglios paraórticos en ningún caso. Dos pacientes presentaron recaída ganglionar paraaórtica durante el seguimiento, recibiendo tratamiento con quimioterapia y quimiorradioterapia de campo extendido, respectivamente. CONCLUSIÓN: En este estudio no se detectó compromiso paraaórtico en pacientes con cáncer cervical IB1 sometidas a histerectomía radical. Este resultado se debe considerar al ofrecer linfadenectomía paraaórtica en pacientes con ganglios pélvicos aparentemente normales en el acto operatorio y/o en los estudios de imágenes prequirúrgicas.

INTRODUCTION: Cervical cancer is a common pathology in developing countries. Radical hysterectomy is the standard of management in early stages without desire for fertility. Paraaortic lymphadenectomy as part of surgical treatment is controversial. The objective of this study is to determine the frequency of paraaortic lymph node involvement in a retrospective series of patients with stage IB1 cervical carcinoma (FIGO 2009 classification) underwent to radical hysterectomy plus pelvic and paraaortic lymphadenectomy at the Instituto Nacional de Cancerologia during the period of January 1 2009 to March 31 2017. METHODS: Descriptive, retrospective study. Clinical, operative, and histopathological variables were described. The frequency of paraaortic, pelvic, concurrent lymph node involvement and adjuvant treatment was determined. A univariate analysis of the variables was performed in the R project statistical software version 3.6.0. RESULTS: 88 cases were included. The mean age was 44,24 ± 9,99 years. The median number of resected pelvic and para-aortic nodes was 23 (6-68) and 4 (1-25), respectively. In 12,5 % of the patients, involvement of the pelvic lymph nodes was present. No patient had paraaortic lymph node involvement. Two patients presented para-aortic lymph node relapse during follow-up, receiving treatment with chemotherapy and extended field chemoradiotherapy, respectively. CONCLUSION: In this study, the frequency of paraaortic involvement in patients with cervical cancer IB1 was 0%. This result should be considered when offering paraaortic lymphadenectomy in patients with apparently normal pelvic nodes in presurgical imaging studies and during the procedure.

Traquelectomía radical laparoscópica en pacientes con cáncer de cuello uterino en estado IB1 en el Instituto de Cancerología - Las Américas, Medellín, Colombia

Objetivo: Revisar nuestra experiencia en traquelectomía radical laparoscópica en cáncer de cérvix en estado temprano. Métodos: Estudio observacional descriptivo retrospectivo de las pacientes que se sometieron a traquelectomía radical laparoscópica en el Instituto de Cancerología - Las Américas, Medellín, Colombia, entre Mayo de 2009 y Enero 2015. Resultados: Se completó satisfactoriamente el procedimiento en 13 pacientes en estadío IB1, 12 (92%) tuvieron tumores menores a 2 cm y una recibió quimioterapia neoadyuvante por un tumor de 3 cm. El tipo histológico más frecuente fue el escamoso en 7 pacientes (54%). En 5 pacientes (38%) no se evidenció enfermedad residual luego del procedimiento. El tiempo quirúrgico promedio fue de 240 min (130-340 min); la mediana de pérdida sanguínea fueron 100 ml (50-200 ml). Dos pacientes tuvieron cistotomía incidental durante la cirugía, reparadas por vía laparoscópica, una de ellas desarrollo una fístula vésico-vaginal que cerró espontáneamente. Ninguna paciente requirió transfusión sanguínea ni conversión a laparotomía. La estancia hospitalaria promedio fue de 1 día (1-3). Dos pacientes requirieron histerectomía laparoscópica. No se han reportado recurrencias ni embarazos con un seguimiento promedio 27,9 meses (8,3-64,4). Conclusión: La traquelectomía radical laparoscópica es factible y se puede realizar de manera segura en un país en desarrollo, en pacientes bien seleccionados, con cáncer de cérvix temprano que desean preservar su fertilidad. Los tiempos de seguimiento aún son cortos para conclusiones definitivas sobre el resultado obstétrico. La seguridad oncológica parece similar a la de la traquelectomía abdominal y/o vaginal.

Objective: To review our experience with laparoscopic radical trachelectomy in patients with early-stage cervical cancer. Methods: We performed a observational descriptive retrospective review of all patients who underwent a laparoscopic radical trachelectomy at the Instituto de Cancerología - Las Americas, Medellin, Colombia, between May 2009 and January 2015. Results: 13 patients completed surgery, 12 patients (92%) were diagnosed as IB1 with tumor size less than 2 cm, and one patient received neoadjuvant chemotherapy due to a 3 cm cervical tumor; histology was squamous cell carcinoma in 7 patients (54%). Five patients (38%) showed no residual disease. The mean surgical time was 240 min (130-340 min); the estimated blood loss was 100 ml (50-200 ml). Two patients had a cystotomy during surgery; one of them developed a vesicovaginal fistula that healed spontaneously. No transfusions were given. No conversions were made. Mean hospital stay 1 day (1-3 day). 2 patients required laparoscopic hysterectomy. To date, no recurrence or pregnancies has been recorded with the median follow up 27.9 months (8.3-64.4 month). Conclusion: Laparoscopic radical trachelectomy is feasible and can be performed safely in a developing country in well-selected patients with early cervical cancer who wish to preserve their fertility. Follow up times are still too short to drive definitive conclusions on obstetric results. The oncological safety appears similar to that of the abdominal trachelectomy and/or vaginal.