Background: Renal medullary carcinoma (RMC) afflicts young persons of African descent with sickle hemoglobinopathies. More than 90% have advanced disease and carry an objective response rate of 29% to RCC therapies with a 13-month median survival. There's a need to develop new ways to screen, diagnose, and treat RMC to raise its survival curve. We established a large RMC cohort and assessed known serum tumor markers with RMC disease severity (e.g.metastatic burden) and correlated marker levels to therapeutic response.
Methods: After IRB-approval, serum markers were captured in primary RMC patients treated at MD Anderson within the past 10 years. Those without serum markers were excluded. Inclusion criteria required RMC diagnosis by either from biopsy or nephrectomy. Using serum tests, known biomarkers in other malignancies were assessed. These markers included CA-125, CEA, AFP, CA19.9, CA15.3 and LDH and trended over time with respect to key clinical events including treatment responses, relapses, and progression of disease.
Results: 18 patients met criteria. Median follow-up was 5.8 months. Median age was 30 years, with 72% male, 94% Black race, and 78% carrying hemoglobinopathy (e.g.sickle-cell trait). Approximately 89% presented metastatic. In metastatic patients, CA-125 was 20-100x above normal, and during treatment convalescence, these values recessed to lower levels. Positive treatment-response resulted in less circulating CA-125 which could be measured over time. LDH and CA-125 were consistently elevated above upper-limit normal ranges, unlike AFP, CA19.9, CA15.3, and CEA. The magnitude of LDH and CA-125 elevation was directly proportional to metastatic burden with CA-125 levels in widely metastatic patients 200+% higher than upper-limit normal.
Conclusions: Trending levels of serum biomarkers such as CA-125 in RMC may assist (1) predicting development or location of metastases, (2) correlate treatment response or efficacy (3) identify a new therapeutic target. Further work to evaluate the expression of markers on the RMC cell surface is ongoing.