A confirmatory trial of modified radical hysterectomy for patients with FIGO stage IB1 cervical cancer with tumor diameter preoperatively estimated at 2 cm or less: Japan Clinical Oncology Group study, JCOG1101

5532 Background: The standard surgery for Stage IB1 uterine cervical cancer is radical hysterectomy (RH, Piver class III hysterectomy). However, RH is highly invasive, and there is a need to establish less invasive techniques. We conducted a single-arm confirmatory trial (JCOG1101) to evaluate the efficacy and safety of modified radical hysterectomy (MRH) in patients with tumor diameter ≤ 2 cm Stage IB1 cervical cancer (jRCT: jRCTs031180167). Methods: From January 2013 to August 2017, 240 patients were enrolled from 40 institutions in Japan. Eligibility criteria included: (1) FIGO 2008 Stage IB1 cervical cancer; (2) histologically proven squamous cell carcinoma, adenocarcinoma (mucinous or endometrioid) or adenosquamous carcinoma; (3) tumor diameter ≤ 2 cm (measured by MRI or conization specimen); and (4) neither distant LN metastasis nor distant metastasis in CT. In case that the cancer could be microinvasive, conization was required to exclude Stage IA cases. The protocol surgery involved cutting the anterior layer of the vesicouterine ligament of the uterus and dissecting regional lymph nodes. Only laparotomy was permitted: laparoscopy and robotic surgery were not allowed. Postoperative irradiation was administered in cases where pelvic LN or parametrial invasion was positive, depth in the cervical wall invasion was ≥ 2/3, or surgical margin was < 1 cm by pathological findings. The primary endpoint was 5-year overall survival (OS). We set the expected 5-year OS of MRH at 95.8% (5-year OS of RH in JCOG0806A, retrospective observational study) and the threshold 5-year OS at 90.8%. Results: Among 225 eligible patients, 193 (85.8%) were pT1b1 (UICC 7th), and 184 (81.8%) had pathological maximal tumor diameter ≤ 2 cm. Parametrial involvement, lymph node metastasis, ≥ 2/3 stromal invasion and < 1 cm surgical margin were observed in 3 (1.3%), 16 (7.1%), 30 (13.3%) and 11 (4.9%) patients, respectively. Thirty-nine patients (17.3%) underwent adjuvant (chemo)radiation. Median follow-up was 77.7 months. Five patients (2.2%) died, and 5-year OS was 98.2% (90% CI: 96.0-99.2, > 90.8%). Thirteen patients (5.8%) relapsed (8 local recurrence and 5 distant recurrence), and 5-year relapse-free survival was 94.7% (95% CI: 90.8-96.9%). Self-urination was observed in all patients, and residual urine disappearance up to 56 days after urethral catheter removal was observed in 213 patients (94.7%). Median time to disappearance of residual urine after urethral catheter removal was 1 day. There was no treatment-related death. Grade 3/4 non-hematological adverse events were observed in 17 patients (7.6%), including 8 infection and 4 hemorrhage. Conclusions: In this study, MRH was as effective as RH and less invasive. MRH can be considered a standard surgery for tumor diameter ≤ 2 cm Stage IB1 uterine cervical cancer. Clinical trial information: UMIN000009726 , jRCTs031180167 .