Kyle A. Blum, MD, MS, is a urologic surgery resident at The University of Kyle A. Blum, MD, MS, a urologic surgery resident at The University of Texas MD Anderson Cancer Center. Blum and his colleagues have discovered a correlation between CA-125 levels, an established biomarker for ovarian cancer, increased tumor burden, and treatment response in patients with renal medullary carcinoma (RMC).

Blum presented findings at the 2022 International Kidney Cancer Symposium from an analysis of CA-125 levels and other serum tumor biomarkers in 32 patients with RMC to see if these markers could be used to monitor disease severity. Only CA-125 and lactate dehydrogenase (LDH) appeared to be elevated in metastatic RMC. Blum notes that LDH tends to be elevated across a broad range of cancers and is considered a nonspecific marker of disease severity.

Blum and his research team cast a wide net, evaluating a range of serum biomarkers known to be related to tumor malignancy in order to elucidate any marker that may yield a high fidelity to treatment response. The signal for CA-125 was very strong, he says, even in a small patient population.

CA-125 appeared to be more sensitive to fluctuations in a patient’s treatment clinical course than LDH. In one representative patient, CA-125 levels dipped with remission or disease convalescence and spiked during adverse events. Furthermore, the patient’s CA-125 level increased shortly before the patient died of their disease.

CA-125 levels were elevated in 82% of patients with metastatic RMC, and CA-125 was above the 100 ng/mL threshold in 58% of patients. This threshold of 100 ng/mL is important, as physicians and researchers treating patients with ovarian cancer have published that a threshold of that level can be suggested as a therapeutic target.

Investigators observed positive clinical correlations between CA-125 levels above the 100 ng/mL threshold and therapies and convalescence in RMC for this biomarker. He says it is exciting to postulate that perhaps this cutoff may be usable in RMC as well. Blum suspects that these results will prompt a several other preclinical studies to further explore the value of CA-125 as a biomarker and potential therapeutic target.

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Kyle A. Blum, MD, MS, says that results from a study of patients renal medullary carcinoma suggest that with CA-125, an established biomarker for ovarian cancer, may play a similar role in this rare disease.

Dr. Blum on Potential of CA-125 as a Biomarker for Renal Medullary Carcinoma

Kyle A. Blum, MD, MS, is a urologic surgery resident at The University of Texas MD Anderson Cancer Center. His research focus includes renal medullary carcinoma (RMC), a highly aggressive subtype of renal cancer that typically affects young adults, often African American, with sickle cell trait. In an interview with 

, he highlights survival data for this patient population. 

Blum says that treatments that work for other renal cancers, such as renal cell carcinoma (RCC) generally are not effective for RMC. Conversely, treatments that work for RMC typically don’t work in RCC or other kidney malignancies. That may could be due to the presence of sickle cell trait in these patients; however, he says that investigators are not sure why RMC behaves differently than other kidney cancers.

Findings from a retrospective study of 165 patients with RMC published in 2015 showed a median overall survival (OS) of 5.0 months (95% CI, 2.4-7.6). OS was better in nonmetastatic patients compared with those who had advanced disease at diagnosis (17.0 vs 4.0 months, respectively; 

Most patients with RMC will develop metastases, and the most recent data, published in 2017, show a median survival of approximately 13 months.  Improved treatment options and understanding of the disease have extended survival since those data were published in 2017, Blum adds, but it is very difficult to conduct randomized controlled trials with such a small patient population.

Surgery is the primary form of treatment. While patients with RCC generally receive upfront nephrectomy, treatment guidelines for RMC recommend consolidative, cytoreductive nephrectomy, Blum says. The goal, he adds, is to shrink the tumor with systemic therapy before proceeding to surgery.

Kyle A. Blum, MD, MS, says that patients with renal medullary carcinoma have poor prognosis, but anecdotal evidence suggests that survival outcomes may be improving.

Dr. Blum Discusses Survival Outcomes for Patients With Renal Medullary Carcinoma

Kyle A. Blum, MD, MS, is a urologic surgery resident at The University of Texas MD Anderson Cancer Center. His research focus includes renal medullary carcinoma (RMC), a highly aggressive subtype of renal cancer that typically affects young adults, often African American, with sickle cell trait. RMC is extremely rare, accounting for just 0.5% to 1% of all renal cancers.

It can be difficult to differentiate RMC from other aggressive renal malignancies using standard histology evaluation, suggesting that prevalence is likely higher than reported. 

Blum says that patients tend to be young men, often complain with nonspecific symptoms, and have advanced disease at diagnosis. Patients may present with belly pain, flank or side pain, fatigue, and/or blood in their urine. These patients may also experience unplanned weight changes or fatigue. These nonspecific symptoms may suggest kidney cancer, but if the patient is a young man male with a large renal mass, Blum says it is important to consider the possibility of RMC. 

He says that conducting electrophoresis to detect the sickle cell trait can also provide a crucial clue. Nearly all patients with RCM also display sickle cell trait. Blum also recommends testing for loss of 

Blum says that the diagnosis of RMC is extremely nuanced and “requires a keen eye.” Because the disease is so rare, relatively few physicians have experience with diagnosis and treatment. A coalition of expert clinicians, researchers, and patient advocates have come together to establish the 

, a nonprofit organization that supports RMC research and educates clinicians, patients, and families about the disease. 

He says that RMC is different from the more common renal cell carcinoma and its pathology is so unique, that it requires a dedicated group of scientists and physicians to regularly update the RMC Alliance website with information regarding diagnosis and management.

Kyle A. Blum, MD, MS, discusses how few physicians have experience with renal medullary carcinoma, and the disease often presents with nonspecific symptoms.

Dr. Blum Discusses the Challenges of Diagnosing Renal Medullary Carcinoma

Kyle A. Blum, MD, MS, is a urologic surgery resident at The University of Texas MD Anderson Cancer Center. He recently published findings suggesting that CA-125 as a potential predictive biomarker in rectal medullary carcinoma (RMC).

RMC is rare, highly aggressive subtype of renal cancer that typically affects young adults with sickle cell trait. In the United States, most patients are African American and 75% are male, Blum says. The disease accounts for 0.5% to 1% of all renal carcinomas, and the condition was only defined in 1995. Most patients who are not metastatic at diagnosis soon develop metastases. In data reported in 2017, the median survival was 13 months.

Surgery is the primary treatment modality, but the RMC Alliance, a consortium of clinicians, researchers, and patient advocates; calls for consolidative, cytoreductive nephrectomy rather than upfront nephrectomy. Blum says treatments that work for RMC typically do not work for other renal cancers and vice versa.

RMC is an understudied condition, but the investigators have evaluated some treatments for the disease and Blum says he is excited to see the results. MD Anderson recently concluded a phase 2 study of patients with RMC who received nivolumab (Opdivo) and ipilimumab (Yervoy). That study accrued 30 patients, which is a fairly large patient population considering the rarity of this disease, and the study is currently in the data synthesis phase.

MD Anderson is also home for a phase 2 study (NCT05347212) of nivolumab plus relatlimab, a human IgG4 LAG-3-blocking monoclonal antibody that restores the effector function of exhausted T cells. The FDA approved this combination, known as Opdualag, in April 2022 for the treatment of patients with advanced melanoma. Investigators, including Blum, hope that this combination can establish an objective response that might suggest physicians can control RMC in patients with clinically advanced or metastatic disease.

Blum is hopeful to see  a dedicated RMC trial with a patient population large enough to produce data that physicians can use when making treatment decisions.

Kyle A. Blum, MD, MS, explains how renal medullary cancer, like most rare cancers, can be difficult to study. However, there are several ongoing studies that include this patient population.

Kyle A. Blum, MD, MS

Articles

Dr. Blum on Potential of CA-125 as a Biomarker for Renal Medullary Carcinoma

Dr. Blum Discusses Survival Outcomes for Patients With Renal Medullary Carcinoma

Dr. Blum Discusses the Challenges of Diagnosing Renal Medullary Carcinoma

Dr. Blum Details Upcoming Research in Renal Medullary Carcinoma