AFP, hCG and LDH in germ cell tumours (IGCCCG risk groups)

What they measure. Non-seminomatous germ cell tumours secrete alpha-fetoprotein from yolk sac elements and beta-human chorionic gonadotropin from trophoblastic elements; pure seminomas never make AFP and only sometimes make hCG. Lactate dehydrogenase reflects tumour bulk. All three are measured at diagnosis, again after orchidectomy (the post-operative values are the ones that count), before each chemotherapy cycle, and at every follow-up visit for years.

What changes. The International Germ Cell Cancer Collaborative Group classification of 1997, updated in 2021, combines the post-orchidectomy marker levels with the primary site and the presence of non-lung visceral metastases to define good, intermediate and poor prognosis groups. Good-risk patients receive three cycles of BEP (bleomycin, etoposide, cisplatin) or four of EP; intermediate and poor-risk patients receive four cycles of BEP or VIP, and poor-risk patients are candidates for intensified trials. The rate at which markers fall during the first cycles predicts outcome, and a slow decline has been used to intensify treatment. After treatment, a rising marker is recurrence and is treated without waiting for a scan to show a mass, while a residual mass with normal markers is resected. Persistently raised AFP without visible disease is one of the few situations in oncology where a blood test alone drives chemotherapy.

Caveats. AFP is also raised by liver disease and some hepatocellular cancers, hCG by pregnancy, marijuana use and some pituitary states, and LDH by haemolysis and almost any cell damage, so a value must be interpreted with the clinical picture and repeated on the same assay. The tests cost a few pounds and are available everywhere, which is one reason germ cell tumours are among the most curable cancers even in low-resource settings. The same markers, hCG above all, run the management of gestational trophoblastic disease, where hCG surveillance after a molar pregnancy is the whole basis of early treatment.