Clinical outcome of recurrent endometrial cancer: analysis of post-relapse survival by pattern of recurrence and secondary treatment.

INTRODUCTION: Recurrence of endometrial cancer is an important clinical challenge, with median survival rarely exceeding 12 months. The aim of this study was to analyze patterns of endometrial cancer recurrence and associations of these patterns with clinical outcome. METHODS: The study included patients with endometrial cancer who underwent primary surgical treatment with or without adjuvant treatment between July 2004 and June 2017 at the Gynaecologic Oncology Unit of one of three tertiary hospitals of the Catholic University Network in Italy with complete follow-up data available. Information on the date and pattern of recurrence was retrieved for each relapse. Post-relapse survival was recorded as the time from the date of recurrence to the date of death or last follow-up. Survival probabilities were compared using log rank tests, and associations of clinico-pathological characteristics with post-relapse survival were tested using Cox's regression models. RESULTS: A total of 1503 patients were included in the analysis. We identified 210 recurrences (14.0%) and 105 deaths (7.0%) at a median follow-up of 34 months (range 1-162). One hundred and fifty-eight recurrences (78.1%) occurred during the first two years of follow-up. Most recurrences were multifocal (n=121, 57.6%) and involved extrapelvic sites (n=38, 65.7%). Parameters associated with post-relapse survival in the univariate analysis included histotype, grade, time to recurrence, pattern of recurrence, number of relapsing lesions, and secondary radical surgery. Only the pattern of recurrence and secondary radical surgery were independent predictors of post-relapse survival in the multivariate analysis (p=0.025 and p=0.0001, respectively). CONCLUSION: Lymph node recurrence and the feasibility of secondary radical surgery were independent predictors of post-relapse survival in patients with recurrent endometrial cancer.

Completion surgery after concomitant chemoradiation in obese women with locally advanced cervical cancer: Evaluation of toxicity and outcome measures.

BACKGROUND: This study aims at comparing the morbidity and oncologic outcomes in normal weight, overweight, and obese women with locally advanced cervical cancers (LACC) submitted to radical surgery after chemoradiation. METHODS: A review of LACC patients with body mass index (BMI) ≥ 18.5 kg/m(2) who underwent neoadjuvant chemoradiation followed by radical surgery between January 1996 and December 2010 was performed. BMI categories were created according to the World Health Organization (WHO) classification. RESULTS: Two hundred sixty-eight women met the inclusion criteria: 118 (44.0%) were normal weight, 100 (37.3%) overweight and 50 (18.7%) obese. The median follow-up was 42 months. Higher BMI was associated with older age (p = 0.0041), while there were no differences among the three groups in Charlson comorbidity score, tumor characteristics, radiotherapy dosing, type of surgery, and pathological response. There were no differences among the three groups in the intraoperative and postoperative complications as well as rate of patients requiring adjuvant treatments: 21 (7.8%) patients experienced grade 3-4 toxicity, including six normal weight, 12 overweight and three obese patients (p = 0.14). Only the rate of grade 1-2 skin toxicity was higher in obese (14%) with respect to overweight (1%) and normal women (0%) (p = 0.00001). There were no differences in the five-year DFS (74%, 77%, and 84% for normal weight, overweight, and obese women, respectively, p = n.s.), and five-year OS (76%, 78%, and 78% for normal weight, overweight, and obese women, respectively, p = n.s.). CONCLUSIONS: The role of obesity should not be overestimated when evaluating the chance of enrolment of LACC patients into preoperative chemoradiation protocols.

Risk Assessment Model for Complications in Minimally Invasive Hysterectomy: A Pilot Study.

Objective: To estimate the rate of intra-operative and postoperative complications, and to define the risk of 30-day major postoperative complications (Clavien-Dindo > 2) according to the presence of one of 10 different variables of minimally invasive (MI) hysterectomy; and then to create a risk assessment model easily applicable in clinical practice. Methods: A single center single arm retrolective study. Data of consecutive patients who have undergone MI hysterectomy for gynaecologic disorders between May 2018 and April 2021 were analyzed. Perioperative surgical outcomes, occurrence of intra- and postoperative complications, and readmissions within 30 days from surgery were registered. Univariate and multivariable analyses were performed to determine the factors associated with major postoperative complications. Results: Over the study period, 445 patients were included in the study. The majority of patients developed a minor event, while major complications (grade III) were required in 14 patients. None of the patients showed a grade IV or V complication. Univariate analysis was performed on patients who had developed intra- or postoperative complications from those who did not experience complications. Body mass index (BMI) (p-value 0.045) and surgeon's experience (p-value 0.015) were found to be associated with a different surgery time. Regarding major postoperative complications, a statistically significant association was found for the variables: BMI (p-value 0.006), previous abdominal surgery (p-value 0.015), and surgeon's experience (p-value 0.035) in the univariate analysis. Also in the multivariate analysis, the risk of major postoperative complications was higher in these three different variables. BMI, previous surgery, and surgeon's experience were inserted in a reproducible risk assessment model in order to stratify the risk of major postoperative complications. Conclusions: We proposed a risk assessment model including factors not previously considered in the literature: the standardization of the surgical technique, the surgeon's experience, the best MI approach (laparoscopy or robot-assisted), and previous abdominal surgery are crucial tools to consider. Further prospective studies with a larger population sample are needed to validate these preliminary evaluations for patients undergoing MI hysterectomy.

Squamous cell carcinoma antigen in patients with locally advanced cervical carcinoma undergoing preoperative radiochemotherapy: association with pathological response to treatment and clinical outcome.

OBJECTIVE: We investigated the role of squamous cell carcinoma (SCC) at presentation (pre-SCC) and after treatment (post-SCC) as predictor of pathological response and outcome in locally advanced cervical cancer (LACC) patients undergoing preoperative chemoradiation. METHODS: One hundred and twenty-three consecutive LACC patients underwent preoperative chemoradiation including cisplatin and 5-fluorouracil plus external radiotherapy to the whole pelvic region. Clinical responders underwent radical surgery. SCC levels were expressed in nanograms/milliliter. RESULTS: Ninety-five of 123 (77.2%) and 15/113 (13.3%) cases were classified as having high pre-SCC and high post-SCC levels. Complete pathological response was documented in 51 cases (41.5%), while persistence of microscopic foci was shown in 40 cases (32.5%). In the univariate analysis, FIGO (International Federation of Gynecology and Obstetrics) stage, clinical response to treatment and post-SCC levels were associated with pathological response to chemoradiation. In the multivariate analysis, only clinical response to treatment and post-SCC levels retained an independent role as predictors of pathological response to treatment. Cases with high post-SCC status had a shorter disease-free survival than cases with low post-SCC levels (p = 0.028). In the multivariate analysis, lack of a pathological complete response/persistence of microscopic foci to treatment retained an independent negative prognostic role for disease-free survival. CONCLUSIONS: Post-SCC identifies LACC patients with a poor chance of pathological response to chemoradiation and an unfavorable outcome.

Prognostic role of Ca125 response criteria and RECIST criteria: analysis of results from the MITO-3 phase III trial of gemcitabine versus pegylated liposomal doxorubicin in recurrent ovarian cancer.

OBJECTIVES: The aim of the study was to investigate i) the association between the Ca125 based and the RECIST assessed response in recurrent ovarian cancer patients enrolled in a Phase III randomized trial (MITO-3) comparing salvage treatment with pegylated liposomal doxorubicin (PLD) versus gemcitabine (GEM); ii) the correlation between the early modifications of Ca125 levels during treatment and the RECIST assessed response; iii) the prognostic value of response based on Ca125 and the RECIST criteria. METHODS: Assessment of response was performed by the RECIST and the GCIG criteria. The prognostic impact of the response by the RECIST criteria and the GCIG criteria was analyzed by the landmark method. RESULTS: Overall, of 30 cases defined as responders on the basis of the GCIG criteria, 20 resulted as responders according to the RECIST criteria (NPV=66.7%); conversely, 93.7% of the cases considered not responders based on the GCIG criteria were defined as unresponsive at RECIST evaluation. Early modifications of Ca125 levels were not completely predictive of the ultimate RECIST defined response. Overall survival (OS) was longer in RECIST defined responders versus non responders, although the statistical significance was not reached (p value=0.092); conversely, median OS was significantly longer in GCIG defined responders than in non responding patients (p value=0.0059). In multivariate analysis, the GCIG assessed response maintained its independent association with OS. CONCLUSIONS: GCIG criteria for tumor response could replace the conventional assessment of response in the decision making process relative to the discontinuation or prolongation of the salvage treatment in ovarian cancer.

Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma.

OBJECTIVE: The purpose of this study was to validate the performance of a laparoscopy-based model to predict optimal cytoreduction in advanced ovarian cancer patients. STUDY DESIGN: In a consecutive prospective series of 113 advanced ovarian cancer patients, the presence of omental cake, peritoneal and diaphragmatic extensive carcinosis, mesenteric retraction, bowel and stomach infiltration, spleen and/or liver superficial metastasis were investigated by laparoscopy. By summing the scores relative to all parameters, a laparoscopic assessment for each patient (total predictive index value = PIV) has been calculated. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy have been calculated for each PIV. RESULTS: The overall accuracy rate of the laparoscopic procedure ranged between 77.3 and 100%. At a PIV >/= 8 the probability of optimally resecting the disease at laparotomy is equal to 0, and the rate of unnecessary exploratory laparotomy is 40.5%. CONCLUSION: The proposed laparoscopic model appears a reliable and flexible tool to predict optimal cytoreduction in advanced ovarian cancer.

Progestin-releasing intrauterine device insertion plus palliative radiotherapy in frail, elderly uterine cancer patients unfit for radical treatment.

The present study investigated the combination of levonorgestrel-releasing intrauterine device (LNG-IUD) insertion and palliative radiotherapy (RT) as a potential approach for treating frail, elderly endometrial cancer (EC) patients considered unfit for curative oncological treatments. The inclusion criteria were an age of ≥65 years, pathological confirmation of a uterine neoplasm, a Charlson comorbidity index (CCI) value of ≥4 and the presence of vaginal bleeding. Patients underwent intrauterine insertion of an LNG-IUD, and thereafter, received a total dose of 30 Gy at 3 Gy per fraction, over 10 days. The clinical target volume (CTV) was defined as the uterus and disease-involved tissues in the pelvis plus a 1-cm margin. The planning target volume was obtained by adding a 1-cm isotropic margin to the CTV. A total of 9 patients with EC (median age, 85 years; Eastern Cooperative Oncology Group performance status ≥2, ≥88.8%; obesity, 55.5%; median CCI, 5) received an LNG-IUD plus RT. An early complete resolution of bleeding was documented in 8 patients (88.8%), while the remaining patient experienced a marked improvement. The median duration of bleeding control was 18 months, while the 2-year actuarial rate of bleeding-free survival was 53.3% (median follow-up time, 20 months; range, 9-60 months). No LNG-IUD- or severe RT-related complications were documented. Overall, a high rate of bleeding remission, durable bleeding-free survival in face of the easy intrauterine insertion of an LNG-IUD and a negligible toxicity profile of the complete treatment were documented in this study, indicating a requirement for further investigation in a larger series.

Excisional cone as fertility-sparing treatment in early-stage cervical cancer.

OBJECTIVE: To describe a case series of early-stage cervical cancer patients treated with excisional cone instead of radical trachelectomy as fertility-sparing surgery. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Early-stage cervical cancer (International Federation of Gynecology and Obstetrics stage IA2-IB1), age ≤ 45 years, tumor ≤ 20 mm. INTERVENTION(S): Cold-knife conization and laparoscopic pelvic lymphadenectomy. MAIN OUTCOME MEASURE(S): Recurrence and pregnancy rate. RESULT(S): There were 17 patients: 4 (23.5%) IA2, 13 (76.5%) IB1; 12 (70.5%) squamous cell carcinoma, 4 (23.5%) adenocarcinoma, and 1 (6%) glassy cell tumor. Four cases (23.5%) involved lymphovascular space invasion. The median number of lymph nodes removed was 18 (range 13-51). None of the patients received neoadjuvant chemotherapy, and two patients (12%) received three courses of adjuvant chemotherapy. No recurrences were observed after a median follow-up of 16 months (range 8-101 months). Two of five patients (40%) attempting to conceive had a spontaneous pregnancy and delivery. CONCLUSION(S): In selected and informed patients, conization and laparoscopic pelvic lymphadenectomy seems to be feasible as a fertility-sparing surgical approach.