Prediction of a potential lethal phenotype in testicular nonseminomatous germ cell tumor.

Abstract

e15575 Background: Cancer is a heterogeneous disease. The nature of heterogeneity provides clues about the biologic origin of cancer. Studying cancer heterogeneity may enable us to elucidate the various subtypes of a particular cancer, and improve the diagnosis, prognostication, and therapy of cancer. Nonseminomatous germ cell tumor (NSGCT) is a prime example of a heterogeneous disease. We determined the lethality of NSGCT by characterizing the histological makeup of primary testicular tumors (proportion of embryonal carcinoma [EC], choriocarcinoma, seminoma, yolk sac tumor [YST], and teratoma) and their tumor burden. Methods: From November 1997 to October 2012, 142 consecutive patients diagnosed with a NSGCT were included for this study. Predictors significant in univariate analysis: tumor stage, tumor size, percentage of YST component, and percentage of EC component were used as predictors of cancer specific death or incurability in a multivariate binary logistic regression model. The outcome of the model is probability of death or incurability. Results: Patient characteristics: age, median (range) – 25 (12-53); race – Caucasians 65%, Hispanics 28%; pathology – embryonal carcinoma 15%, teratoma 6%, mixed NSGCT 79%; stage – I 43%, II 33%, III 24%; size of primary tumor, median (range) – 3.8 cm (0.9-27); HCG<5,000 95%, >5,000 4%; AFP<1,000 85%, >1,000 13%; therapy – salvage chemotherapy 15%, RPLND 34%, HD chemotherapy w/ SCT 1%, WBRT 1%. Univariate analysis showed that clinical stage (p=.0001), presence of YST (p<.005), size of primary tumor (p=.005), and absence of EC (<.01) have prognostic significance. We developed a nomogram to identify patients who are most likely to succumb to their NSGCT based on the histologic makeup of their primary tumor, size of the primary tumor, initial tumor markers, and appropriate surgeries after chemotherapy. Conclusions: Presence of YST in advanced NSGCT predicts chemotherapy resistance in a potentially lethal phenotype. Early diagnosis and timely treatment with chemotherapy and surgery may improve the clinical outcome of these patients. Results of this study need to be validated in another data base or a prospective clinical trial.