Prospective multimodal imaging assessment of locally advanced cervical cancer patients administered by chemoradiation followed by radical surgery. The PRICE (PRospective Imaging of CErvical cancer and neoadjuvant treatment) study: the role of ultrasound

Objective Chemoradiation-based neoadjuvant treatment followed by radical surgery is an alternative therapeutic strategy for locally advanced cervical cancer (LACC) –stage ≥ IB2 (except of IIA1)– but ultrasound variables used to predict neoadjuvant partial response are not well defined. The goal of this study was to prospectively analyze the potential role of transvaginal ultrasound (TVUS) in early predicting pathologically assessed residual disease in a large, single-institution series of LACC patients triaged to neoadjuvant treatment followed by radical surgery. Methods Between October 2010 and June 2014, 108 women with histologically documented LACC were screened and 88 of them were included in the final analysis. Tumor volume, 3D power Doppler indices and contrast parameters were obtained before (baseline examination) and after two weeks of treatment (early examination). The pathological response was defined as complete (absence of any residual tumor after treatment) or partial, including both microscopic and macroscopic residual tumor at pathological examination. Comparisons between the two groups (complete response group versus partial response group) were made with Mann–Whitney-test or Wilcoxon-test and χ2-test, as appropriate. Receiver–operating characteristic (ROC) curves were generated for statistically significant ultrasound variables on univariate analysis to evaluate their diagnostic ability to predict pathological partial response. Results Complete and partial pathological responses to neoadjuvant therapy were documented in 40 (45.5%) and 48 (54.5%) patients respectively. At baseline examination, tumor volume did not differ between patients with a complete and those with a partial response. However, after two weeks of neoadjuvant treatment, the tumor volume was significantly higher in patients with partial response than in those with complete response (p = 0.019). Among the 3D vascular indices, vascularization index (VI) was significantly lower in partial response group than in complete response group both before and two weeks after treatment (p = 0.037 and p = 0.024 respectively). In the contrast analysis, a lower tumor peak enhancement (PE) as well as a lower tumor Wash in Rate (WiR), and a longer tumor Rise Time (RT) were observed at baseline examination in women with partial response than in those with complete response (p = 0.006, p = 0.003, p = 0.038, respectively). No difference was found in terms of contrast parameters at early examination. Receiver operating characteristic (ROC) curve analysis of baseline parameters showed that the best cut-off for predicting pathological partial response was 41.5% for VI (sensitivity 63.6% and specificity 66.7%); 16123.5 for tumor PE (sensitivity 47.9% and specificity 84.2%); 7.8 s for tumor RT (sensitivity 68.8% and specificity 57.9%); and 4902 for tumor WiR (sensitivity 77.1% and specificity 60.5%). ROC curves of early parameters showed that the best cut-off for predicting pathological partial response was 18.1 cm3 for tumor volume (sensitivity 71% and specificity 60%) and 39.5% for VI (sensitivity 63% and specificity 74%). Conclusions Ultrasound and contrast parameters differ between patients with complete response and those with partial response before and after two weeks of neoadjuvant treatment. However, neither ultrasound parameters performed before treatment nor those performed two weeks after treatment have shown a cut-off value with acceptable sensitivity and specificity for predicting pathological partial response to neoadjuvant therapy.