Purpose: Increasing new blood vessel formation (neoangiogenesis) within tumors is an adverse prognostic factor for survival in several cancers. Neoangiogenesis is usually determined histopathologically and not in vivo. To assess neoangiogenesis in vivo, we have used Doppler ultrasonography (US) to measure the uterine artery pulsatility index (UAPI) in patients with gestational trophoblastic tumors (GTTs). Here, we assess whether the UAPI can provide independent prognostic information predictive of methotrexate resistance (MTX-R), a drug central to the management of GTT.
Experimental design: All patients treated for GTTs between March 1994 and January 1999 had their records reviewed to determine their pretreatment Charing Cross Hospital (CXH) prognostic score, uterine volume, the lowest UAPI of either uterine artery, number of metastases, and human chorionic gonadotropin (hCG) concentration. Of the 164 patients for whom all data were available, 47 subsequently developed MTX-R, defined as a plateaued or rising hCG in two consecutive samples.
Results: UAPI, hCG, uterine volume, presence of metastases, and the overall CXH prognostic score were all predictive of MTX-R on univariate analysis. Moreover, the UAPI remained a significant independent predictor of MTX-R on multiple logistic regression analysis. After adjustment for the CXH prognostic score, the odds ratio for the risk of MTX-R in patients with a UAPI < or =1 compared with those with a UAPI >1 was 2.68 (95% confidence interval, 1.25-5.74; P = 0.01). The unadjusted odds ratio for the above comparison was 2.32 (95% confidence interval, 1.14-4.7; P = 0.02).
Conclusions: The UAPI, as an indirect in vivo measure of functional tumor vascularity, independently predicts the response to chemotherapy in GTTs.