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BackgroundHigh-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA) represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools.Methods and FindingsTumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT) scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival.ConclusionsDetection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic dilemma and a potential critical inflection point in precision medicine. This study suggests that the use of personalized ctDNA biomarkers in gynecologic cancers can identify the presence of residual tumor while also more dynamically predicting response to treatment relative to currently used serum and imaging studies. Of particular interest, ctDNA was an independent predictor of survival in patients with ovarian and endometrial cancers. Earlier recognition of disease persistence and/or recurrence and the ability to stratify into better and worse outcome groups through ctDNA surveillance may open the window for improved survival and quality and life in these cancers.

To determine whether total laparoscopic radical hysterectomy (TLRH) is a feasible alternative to an abdominal radical hysterectomy (ARH) in a gynecologic oncology fellowship training program. We prospectively collected cases of all of the patients with cervical cancer treated with TLRH and pelvic lymphadenectomy by our division from 2000 to 2006. All of the patients from the TLRH group were matched 1:1 with the patients who had ARH during the same period based on stage, age, histological subtype, and nodal status. Thirty patients were treated with TLRH with a mean age of 48.3 years (range, 29-78 years). The mean pelvic lymph node count was 31 (range, 10-61) in the TLRH group versus 21.8 (range, 8-42) (P < 0.01) in the ARH group. Mean estimated blood loss was 200 cc (range, 100-600 cc) in the TLRH with no transfusions compared to 520 cc in the ARH group (P < 0.01), in which five patients required transfusions. Mean operating time was 318.5 min (range, 200-464 min) compared to 242.5 min in the ARH group (P < 0.01), and mean hospital stay was 3.8 days (range, 2-11 days) compared to 5.6 days in the ARH group (P < 0.01). All TLRH cases were completed laparoscopically. All patients in the TLRH group are disease free at the time of this report. In conclusion, it is feasible to incorporate TLRH training into the surgical curriculum of gynecologic oncology fellows without increasing perioperative morbidity. Standardization of TLRH technique and consistent guidance by experienced faculty is imperative.

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