CEA Emerges as a Potential Prognostic Marker for Lu-177 PSMA Therapy

A simple blood test normally associated with colorectal cancer could provide additional information about how men with metastatic castration-resistant prostate cancer fare after 177Lu-PSMA-617 therapy. A new prospective study of 142 patients found that elevated carcinoembryonic antigen (CEA) before treatment was independently associated with shorter progression-free and overall survival.

The finding does not mean that patients with elevated CEA should avoid 177Lu-PSMA. The study had no control group receiving another treatment, so CEA has so far been shown to be a prognostic marker, identifying patients with poorer outcomes, rather than a predictive marker showing who will or will not benefit specifically from 177Lu-PSMA.

After a median follow-up of 44 months, median progression-free survival was 7.0 months and overall survival 16.8 months. Even after accounting for PSA, alkaline phosphatase, haemoglobin, previous docetaxel and other clinical factors, higher CEA remained independently associated with poorer progression-free survival  and overall survival.

Perhaps the most interesting finding was that CEA and PSA were essentially unrelated. This suggests that the two blood markers may be capturing different aspects of prostate cancer biology. PSA performed better as an individual prognostic marker, but combining CEA with PSA improved the ability to distinguish patients with better and worse outcomes.

Elevated CEA may identify a particularly aggressive form of advanced prostate cancer rather than simply greater tumour burden. Previous research has linked CEA with aggressive-variant prostate cancer and liver metastases. In this study, CEA was not associated with the extent of bone disease on PSMA PET and showed little relationship with conventional neuroendocrine markers, suggesting it may be identifying a distinct biological phenotype.

There are also important limitations. Patients received lower 177Lu-PSMA activities than the currently approved Pluvicto regimen, and the findings need confirmation in independent cohorts treated with modern dosing. Nevertheless, CEA is inexpensive, widely available and easy to measure. If these results are validated, adding CEA to PSA and other routine blood tests could provide another simple window into the biology of advanced prostate cancer before PSMA radioligand therapy.

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