Validation of tumour-free distance as novel prognostic marker in early-stage cervical cancer: a retrospective, single-centre, cohort study

Background The aim of the present study was to assess the prognostic value of tumour-free distance (TFD), defined as the minimum distance of uninvolved stroma between the tumour and peri-cervical stromal ring, in early-stage cervical cancer. Methods Patients with pathologic FIGO 2009 stage IA1-IIA2 cervical cancer, treated by primary radical surgical treatment between 01/2000 and 11/2019, were retrospectively included. Adjuvant treatment was administered according to the presence of previously established pathologic risk factors. TFD was measured histologically on the hysterectomy specimen. Pre-operative TFD measured at MRI-scan from a cohort of patients was reviewed and compared with pathology TFD. Results 395 patients were included in the study. 93 (23.5%) patients had TFD <= 3.0 mm and 302 (76.5%) had TFD > 3.0 mm. TFD <= 3.0 mm together with lymph vascular space involvement represented the strongest predictor for lymph node metastasis at multivariate analysis. TFD <= 3.0 mm was associated with worse 5-year disease-free survival (DFS) and overall survival (OS), compared with TFD > 3.0 mm (p = 0.022 and p = 0.008, respectively). DFS difference was more evident in the subgroup of patients with low-risk factors who did not receive adjuvant treatment (p = 0.002). Cohen's kappa demonstrated an agreement between TFD measured at pre-operative MRI-scan and histology of 0.654. Conclusions Pathologic TFD <= 3.0 mm represents a poor prognostic factor significantly associated with lymph node metastasis and it may be considered a novel marker to select candidates for adjuvant treatment. The possibility to obtain this parameter by radiological imaging makes it a potential easy-measurable pre-operative marker to predict the presence of high-risk pathologic factors in early-stage cervical cancer.

Automated summary

The study found that tumor-free distance (TFD) ≤ 3.0 mm, combined with lymph vascular space involvement, was the strongest predictor for lymph node metastasis. TFD ≤ 3.0 mm was associated with worse 5-year disease-free survival and overall survival compared to TFD > 3.0 mm. The difference in disease-free survival was particularly significant in patients with low-risk factors who did not receive adjuvant treatment.