CA-125 Level Correlates With Response, Progression in Renal Medullary Cancer

Kyle A. Blum, MD, MS

CA-125 levels increased as renal medullary carcinoma (RMC) worsened and decreased with treatment response, according to findings presented during the 2022 International Kidney Cancer Symposium.¹

Kyle A. Blum, MD, MS, a urologic surgery resident at The University of Texas MD Anderson Cancer Center, presented results from a retrospective study of 33 patients with available serum tumor markers. He said that confirming CA-125 as a biomarker for RMC would have important and exciting implications for this patient population.

“It’s a reproducible and easily accessible clinical study,” he said during his presentation at the meeting. “It’s a serum marker for blood draws. There’s a potential that it can be a marker of disease response and progression, kind of like when we use [prostate-specific antigen] in [prostate cancer]. Then, there’s a significant potential for therapeutic targeting that may happen as well.”

Investigators found elevated LDH and CA-125 levels at baseline. At any point, CA-125 levels were elevated in 82% of patients with metastatic RMC. Furthermore, CA-125 was above the 100 ng/mL threshold in 58% of patients.

“That number is actually in the ovarian cancer clinical trial literature,” Blum said. “That gives them kind of the threshold for saying what is therapeutically targetable. So, while I am not sure if there’s a 1:1 relationship between that literature and RMC, it is interesting to note that we are above that threshold in at least two-thirds of this small sample size.”

RMC is a rare but often fatal kidney cancer—fewer than 5% of patients survive longer than 3 years. Furthermore, RMC is uniquely resistant to existing therapies for clear cell renal cell carcinoma.

The disease primarily affects people of African ancestry aged 11 to 39, and almost exclusively in those with sickle hemoglobinopathies. The most common symptoms at presentation include gross hematuria, flank pain, and abdominal masses. These disease affects those assigned male at birth (AMAB) twice as often and usually appears in the right kidney for unknown reasons.²

In data from one trial of 52 patients, the median overall survival (OS) for all patients was 13.0 months. Investigators observed that median OS was superior in patients who underwent nephrectomy (n = 38) compared with those who were treated with systemic therapy only (16.4 vs 7.0 months, P < .001).³

The overall objective response (ORR) was 29% (13/45) with chemotherapy. Among 28 patients who received targeted therapies, the median therapy duration was 8 weeks and investigators observed no objective responses. Only 7 patients (13%) survived longer than 24 months.

Blum and his colleagues analyzed patients for CA-125 and other serum tumor biomarkers (AFP, LDH, b2 microglobulin, CA-19.9, CA-15.3, CEA, and bHCG) to see if these markers could be used to monitor disease severity. He said that only CA-125 and LDH appeared to be elevated in metastatic RMC.

Twenty-three (69.7%) patients in cohort were AMAB and the median patient age was 35 years (interquartile range, 22.0-39.0). Thirty-two (96.9%) were Black, 18 (54.5%) had left-side disease, and 31 (93.9%) were metastatic at diagnosis. Thirty-one (93.9%) patients had sickle trait, 1 (3.0%) had sickle B thalassemia, and 1 had no sickle hemoglobinopathy.

Blum said that CA-125 appeared to be more sensitive to fluctuations during clinical course than LDH. Looking at 1 representative patient, he said that CA-125 level dipped with remission and spiked during adverse events. He added that CA-125 level increased shortly before the patient died.

Investigators also identified a correlation between CA-125 level and metastatic burden and the number of metastatic sites. “If you have a patient with 1 metastatic site, you have a median CA-125 of 11 [U/mL], which is well below even the normal range. And then if you have 4 or more [sites], you’re upwards of 200 [U/mL].”

Blum et al were surprised to discover that CA-125 levels were nearly twice as high in patients assigned female at birth (AFAB). That would suggest that patients who were AFAB had a greater metastatic burden, but Blum said that did not appear to be the case.

References

1. Blum KA. Biomarkers of disease burden and treatment in response in renal medullary carcinoma. Presented at: 2022 International Kidney Cancer Symposium; November 4-5, 2022; Austin, TX.
2. Beckermann KE, Sharma D, Chaturvedi S, et al. Renal medullary carcinoma: establishing standards in practice. J Oncol Pract. 2017 Jul;13(7):414-421. doi:10.1200/JOP.2017.020909
3. Shah AY, Karam JA, Malouf GG, et al. Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study. BJU Int. 2017 Dec;120(6):782-792. doi:10.1111/bju.13705