Updated Recommendations on the Diagnosis, Management, and Clinical Trial Eligibility Criteria for Patients With Renal Medullary Carcinoma

Abstract

Renal medullary carcinoma (RMC) is one of the most aggressive renal cell carcinomas. It predominantly afflicts young adults and adolescents with sickle cell trait and other sickle hemoglobinopathies, and is refractory to targeted and antiangiogenic therapies used in patients with clear-cell renal cell carcinoma. Platinum-based cytotoxic chemotherapy is the mainstay for RMC treatment. On the basis of recent advances in the diagnosis, management, and clinical trial development for RMC, a panel of experts met in October 2017 and developed updated consensus recommendations to inform clinicians, researchers, and patients. Because RMC often aggressively recurs while patients are still recovering from nephrectomy, upfront chemotherapy should be considered for most patients, including those with localized disease. After safety and dosing information has been established in adults, phase II and III trials enrolling patients with RMC should allow patients aged 12 years and older to be accrued. Patients with the very rare unclassified renal cell carcinoma with medullary phenotype variant should be included in RMC trials. Medical providers should be aware that RMC can afflict subjects of all races, and not only those of African descent, and that the presence of sickle cell trait, or of other sickle hemoglobinopathies, can affect drug responses and toxicity.

Keywords: INI1; Renal cell carcinoma; SMARCB1; Sickle hemoglobinopathies; Unclassified renal cell carcinoma with medullary phenotype.

Figure 1:

Diagnosis and management recommendations for renal medullary carcinoma (RMC) and renal cell carcinoma, unclassified with medullary phenotype (RCCU-MP). FH-deficient RCC: fumarate hydratase-deficient renal cell carcinoma; RCC: renal cell carcinoma; RPLND: retroperitoneal lymph node dissection *Whenever possible, fresh frozen tissue should be saved for research use. ^#RMC tumor tissues always contain sickled erythrocytes, often demonstrate reticular/yolk sac tumor-like patterns, and lack the tubulocystic patterns seen in FH-deficient RCCs. Secondary review of the pathology at specialized centers is strongly encouraged. ^§Upfront surgery can be considered for isolated tumors ≤4 cm in greatest dimension, confined to the kidney. These patients should be followed closely post-operatively with history, physical, and imaging. ^¥Cytoreductive radical nephrectomy should be considered if feasible based on response to systemic therapy, performance status, and surgical evaluation.