Gabriel Rendon

ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer

The objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer. From April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2-IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size 100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23-67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients-that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0-68.3). Three patients developed recurrent disease within 2 years of surgery-that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%). Our prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.

Incidence of adverse events in minimally invasive vs open radical hysterectomy in early cervical cancer: results of a randomized controlled trial

Standard treatment of early cervical cancer involves a radical hysterectomy and retroperitoneal lymph node dissection. The existing evidence on the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer is either nonrandomized or retrospective. The purpose of this study was to compare the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer. The Laparoscopic Approach to Carcinoma of the Cervix trial was a multinational, randomized noninferiority trial that was conducted between 2008 and 2017, in which surgeons from 33 tertiary gynecologic cancer centers in 24 countries randomly assigned 631 women with International Federation of Gynecology and Obstetrics 2009 stage IA1 with lymph-vascular invasion to IB1 cervical cancer to undergo minimally invasive (n = 319) or open radical hysterectomy (n = 312). The Laparoscopic Approach to Carcinoma of the Cervix trial was suspended for enrolment in September 2017 because of an increased risk of recurrence and death in the minimally invasive surgery group. Here we report on a secondary outcome measure: the incidence of intra- and postoperative adverse events within 6 months after surgery. Of 631 randomly assigned patients, 536 (85%; mean age, 46.0 years) met inclusion criteria for this analysis; 279 (52%) underwent minimally invasive radical hysterectomy, and 257 (48%) underwent open radical hysterectomy. Of those, 300 (56%), 91 (16.9%), and 69 (12.8%) experienced at least 1 grade ≥2 or ≥3 or a serious adverse event, respectively. The incidence of intraoperative grade ≥2 adverse events was 12% (34/279 patients) in the minimally invasive group vs 10% (26/257) in the open group (difference, 2.1%; 95% confidence interval, -3.3 to 7.4%; P=.45). The overall incidence of postoperative grade ≥2 adverse events was 54% (152/279 patients) in the minimally invasive group vs 48% (124/257) in the open group (difference, 6.2%; 95% confidence interval, -2.2 to 14.7%; P=.14). For early cervical cancer, the use of minimally invasive compared with open radical hysterectomy resulted in a similar overall incidence of intraoperative or postoperative adverse events.

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.

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.

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.

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.

MILACC study: could undetected lymph node micrometastases have impacted recurrence rate in the LACC trial?

The etiology of inferior oncologic outcomes associated with minimally invasive surgery for early-stage cervical cancer remains unknown. Manipulation of lymph nodes with previously unrecognized low-volume disease might explain this finding. We re-analyzed lymph nodes by pathologic ultrastaging in node-negative patients who recurred in the LACC (Laparoscopic Approach to Cervical Cancer) trial. Included patients were drawn from the LACC trial database, had negative lymph nodes on routine pathologic evaluation, and recurred to the abdomen and/or pelvis. Patients without recurrence or without available lymph node tissue were excluded. Paraffin tissue blocks and slides from all lymph nodes removed by lymphadenectomy were re-analyzed per standard ultrastaging protocol aimed at the detection of micrometastases (>0.2 mm and ≤2 mm) and isolated tumor cells (clusters up to 0.2 mm or <200 cells). The study included 20 patients with median age of 42 (range 30-68) years. Most patients were randomized to minimally invasive surgery (90%), had squamous cell carcinoma (65%), FIGO 2009 stage 1B1 (95%), grade 2 (60%) disease, had no adjuvant treatment (75%), and had a single site of recurrence (55%), most commonly at the vaginal cuff (45%). Only one patient had pelvic sidewall recurrence in the absence of other disease sites. The median number of lymph nodes analyzed per patient was 18.5 (range 4-32) for a total of 412 lymph nodes. A total of 621 series and 1242 slides were reviewed centrally by the ultrastaging protocol. No metastatic disease of any size was found in any lymph node. There were no lymph node low-volume metastases among patients with initially negative lymph nodes who recurred in the LACC trial. Therefore, it is unlikely that manipulation of lymph nodes containing clinically undetected metastases is the underlying cause of the higher local recurrence risk in the minimally invasive arm of the LACC trial.

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.