Inge Peters

New windows of surgical opportunity for gynecological cancers in the era of targeted therapies

Precision medicine through molecular profiling has taken a prominent role in the treatment of solid tumors and it is widely expected that this will continue to expand. With respect to gynecological cancers, a major change has particularly been observed in the treatment landscape of epithelial ovarian, endometrial, and cervical cancers. Regarding the former, maintenance therapy with either poly(ADP-ribose) polymerase inhibitors (PARPi) and/or bevacizumab has become an indispensable treatment option following the traditional combination of cytoreductive surgery and platinum-based chemotherapy. Considering endometrial cancer, the molecular classification system has now been incorporated into virtually every guideline available and molecular-directed treatment strategies are currently being researched, presumably leading to a further transformation of its treatment paradigm. After all, treatment with immune-checkpoint inhibitors that target the programmed cell death 1 (PD-1) receptor has already been shown to significantly improve disease outcomes in these patients, especially in those with mismatch repair deficient, microsatellite stability-high (MMRd-MSI-H) disease. Similarly, in recurrent/metastatic cervical cancer patients, these agents elicited improved survival rates when being added to platinum-based chemotherapy with or without bevacizumab. Interestingly, implications of these targeted therapies for surgical management have been touched on to a minor extent, but are at least as intriguing. This review therefore aims to address the wide-ranging opportunities the molecular tumor characteristics and their corresponding targeted therapies have to offer for the surgical management of epithelial ovarian, endometrial, and cervical cancers, both in the primary and recurrent setting.

Evaluation of the one-step nucleic acid amplification method for rapid detection of lymph node metastases in endometrial cancer: prospective, multicenter, comparative study

To evaluate the diagnostic performance of the one-step nucleic acid amplification (OSNA) method for the detection of sentinel lymph node (SLN) metastases in women with apparent early-stage endometrial cancer compared with standard ultrastaging. Prospective, multicentric, interventional study. Patients with apparent early-stage endometrial cancer who underwent primary surgical staging with SLN mapping were included. SLNs were serially sectioned with 2 mm slices perpendicular to the longest axis of the node: the odd slices were submitted to ultrastaging, whereas the even slices were submitted to the OSNA analysis. Diagnostic performance was calculated taking ultrastaging as referral standard. Three-hundred and sixteen patients with 668 SLNs were included. OSNA assay detected 22 (3.3%) positive SLNs, of which 17 (2.5%) were micrometastases and 5 (0.7%) macrometastases, whereas ultrastaging detected 24 (3.6%) positive SLNs, of which 15 (2.2%) were micrometastases and 9 (1.3%) macrometastases (p=0.48). Regarding negative SLNs, OSNA detected 646 (96.7%) negative nodes, including 8 (1.2%) isolated tumor cells, while ultrastaging detected 644 (96.4%) negative nodes with 26 (3.9%) isolated tumor cells. Specificity of OSNA was 98.4% (95% CI 97.5 to 99.4), accuracy was 96.7% (95% CI 95.4 to 98.1), sensitivity was 50% (95% CI 30.0 to 70.0), while negative predictive value was 98.1% (95% CI 97.1 to 99.2). Discordant results were found in 22 SLNs (3.3%) corresponding to 20 patients (6.3%). These were 10 (1.5%) false-positive SLNs (all micrometastases): one (0.1%) of these was a benign epithelial inclusion at ultrastaging. There were 12 (1.8%) false-negative SLNs of OSNA, of which 9 (1.3%) were micrometastases and 3 (0.5%) macrometastases. Overall, 17/668 (2.5%) benign epithelial inclusions were detected at ultrastaging. The OSNA method had high specificity and high accuracy in detecting SLN metastasis in apparent early-stage endometrial cancer. The advantage of the OSNA method could be represented as the possibility to analyze the entire lymph node thus eliminating sampling bias.

PARP inhibitors in epithelial ovarian cancer: what are their potential implications for surgical management?

Low-grade serous ovarian cancer in pregnancy

How should randomized controlled trials in epithelial ovarian cancer be interpreted?

Evaluation of decision regret and reproductive concerns following fertility-sparing treatment in adolescents and young adults with atypical endometrial hyperplasia or endometrioid endometrial cancer-a single-center cross-sectional study.

To examine decision regret and reproductive concerns following fertility-sparing treatment in adolescents and young adults (defined as aged 15-39 years) with endometrial atypical hyperplasia or endometrioid endometrial cancer. All adolescents and young adults diagnosed with endometrial atypical hyperplasia or endometrioid endometrial cancer between January 1, 2021, and December 31, 2023, who underwent fertility-sparing treatment at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS hospital in Rome, Italy, were contacted. Patients were asked to fill out the 5-item Decision Regret Scale score and the 18-item Reproductive Concerns After Cancer score, assessing the following areas of concern: fertility potential, partner disclosure of fertility status, child's health, personal health, acceptance of possible infertility, and becoming pregnant. Thirty-two patients gave informed consent and were included. Complete treatment response was achieved in 93.9% of cases, whereas among those with endometrioid endometrial cancer the complete response rate was 100.0%. After a median follow-up of 29 months (range; 11-44 months), 1 patient (3.1%) experienced persistent disease and 6 patients (18.8%) had a relapse. Five patients (15.6%) underwent hysterectomy. Among the 20 patients who tried to conceive following diagnosis, a total of 12 pregnancies were achieved in 11 patients (pregnancy rate 60.0%). The live birth rate per pregnancy was 66.7%; 2 pregnancies were still ongoing. Mean Decision Regret Scale score was 16.6 (SD 24.0, range; 0-100). Mean Reproductive Concerns After Cancer score for all items was 2.78 (SD 1.17, range; 1-5), with greatest concern for acceptance of possible infertility (mean 3.23, SD 1.08), fertility potential (mean 3.12, SD 1.24) and child's health (mean 3.02, SD 1.31). Regardless favorable oncological and obstetrical outcomes and mild decision regret, reproductive concerns are common following fertility-sparing treatment in adolescents and young adults with endometrial atypical hyperplasia or endometrioid endometrial cancer.