Major prognostic value of modeled AUChCG-AFP, a dynamic kinetic marker characterizing tumor marker decline of nonseminomatous germ cell tumors (NSGCT) intermediate-poor-risk patients according to the IGCCCG

Abstract

5085 Background: The level of human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP) serum tumor marker is well established in NSGCT as prognostic factor, the relevance of marker kinetic analysis under treatment is still unclear. This may be due to the inaccuracy of methods employed so far, simplifying complex exponential decrease curves by a median half-life (HL). We propose to model patient's AFP and hCG decline profiles in order to calculate area under the curve of marker concentrations versus time (AUChCG-AFP) and to test its prognostic value. Methods: Our retrospective study involved 65 pts treated by 4 cycles of bleomycin-etoposide-cisplatin (BEP) regimen for an intermediate-poor-risk group NSGCT in the same center between 1997 and 2008. A kinetic population approach with NONMEM software was used to model equations of hCG and AFP individual decrease profiles between day 7 (D7) and D42 after the first BEP cycle. AUChCG and AUCAFP were calculated between day D0 and D42 as: AUC0–42=AUC0–7+AUC7–42 where AUC0–7 = trapezium area between D0 and D7 while AUC7–42=integral of modeled equation. Survival univariate and multivariate analyses tested the prognostic value of AUChCG-AFP regarding PFS. Results: Mono-exponential models best fitted AFP and hCG decreases: CAFP (t) = 381*e - 0.14 *t +3.27 and ChCG (t) = 1230*e - 0.25 *t +1.22. Three prognostic groups (AUChCG-AFP) were determined according to AUCAFP median and AUChCG terciles: good if AUCAFP<=11729.4 and AUChCG0–42<=6670; intermediate if AUCAFP>11729 and/or if 6670<=AUChCG<18178 and poor risk if AUChCG>18178 whatever AUCAFP. AUChCG-AFP was a significant prognostic factor in the univariate analysis on the 2 year PFS (100% vs 73.8% vs 67.7%, p = 0.035) as well as IGCCCG score (poor/intermediate risk groups), primary site (mediastinal/other) and HLhCG-AFP. Yet AUChCG-AFP was the only significant independent factor in the multivariate Cox model (HR = 3.3, 95%CI = [1.2–9.2], p = 0.032). Conclusions: Modeled AUChCG-AFP is a dynamic kinetic marker characterizing NSGCT patient marker decline during BEP treatment. These results must be validated in a prospective cohort. It may be a major prognostic factor. No significant financial relationships to disclose.