Serum tumor marker half-life during chemotherapy allows early prediction of complete response and survival in nonseminomatous germ cell tumors

Abstract

The prognostic value and therapeutic utility of monitoring the decay of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) after chemotherapy for nonseminomatous germ cell tumors was assessed. Patients treated on successive front line chemotherapy protocols at Memorial Hospital between 1979 and 1988 were studied. Marker values taken within the first 90 days of treatment were reviewed for the 198 patients who had initially abnormal values and serial measurements at Memorial Hospital. Since markers frequently increased in an unpredictable fashion in the first week after chemotherapy, prechemotherapy values would be inaccurate for assessment of subsequent half-life. Therefore, the first two values measured greater than 7 days after the start of treatment were used for all calculations of half-life. Among 38 patients who had the two successive AFP measurements elevated, those who later achieved a complete response (CR) had a median AFP half-life of 6.1 days (n = 20), whereas those not achieving CR had a median AFP half-life of 13.3 days (P = 0.02). Among 37 patients with the two successive HCG values elevated, those who later achieved CR had a median HCG half-life of 4.2 days (n = 10), whereas those not achieving CR had a median HCG half-life of 18.4 days (P = 0.04). Forty-two patients who had an AFP half-life greater than 7 days or an HCG half-life greater than 3 days had significantly shorter overall survival (median, 8 months) than the other 156 patients (median not reached) (P less than 0.0001). These 42 patients also achieved CR in lower proportion (29%) than the other 156 patients (89%) (P less than 0.0001). Cox regression identified prolonged marker half-life as the most significant independent predictor of survival. Lack of appropriate decay of serum tumor markers can identify patients unlikely to achieve CR or prolonged survival and thus can be used to select patients during treatment who may benefit from an early change to more aggressive therapy.