Renal cell carcinoma (RCC) is a heterogeneous group of cancer resulting from renal tubular epithelial cells and is one of the top ten cancers worldwide
8. RCC is the most common type of renal tumor, which is about five percent of all cancers in men and three percent in women, with an increased incidence in the last decade
9. According to the Surveillance Epidemiology and End Results (SEER; the United States) database, the mean age of RCC patients is 64 years, and has almost a normal distribution. If someone younger than 46 years of age (lowest decimal of the age distribution) is diagnosed with RCC, the possibility of an underlying hereditary kidney cancer syndrome should be taken into account as it accounts for 3–5% of all RCCs
10. Most common metastasis in RCC occurs to the lung, retroperitoneum, bone, and brain, and to the liver to a lesser extent
11. We also observed lung metastasis in our patient.
For patients with surgically resectable RCC, the standard of care is partial or radical nephrectomy and surgical excision with a curative intent. However, patients with inoperable or metastatic RCC are systematically treated with target agents and/or immune control point inhibitors. RCC is very vascular, and therefore, sorafenib, sunitinib, pazopanib, axitinib, lenvatinib, and cabozantinib, which are tyrosine kinase inhibitors targeting the VEGF signaling axis, are used for first- and secondline metastatic RCC therapy12-14. Agents targeting the mammalian target of rapamycin are used. Recent studies have focused on the combination of anti-VEGF therapy with new generation immune control point inhibitors, such as antibodies against the programmed cell death protein ligand 1 (PDL1) (avelumab and atezolizumab) and 1 (PD1) (nivolumab and pembrolizumab)15. Another combination (Checkmate 214, NCT02231749) is nivolumab with ipilimumab, the latter of which is an inhibitor of the T cell control point cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)16. This combinations are recommended at the category 1 level of the first-line therapy for metastatic RCC patients, who are at middle and high-risk. Our patient was at high risk but could not receive that combination for treatment because his health insurance did not cover it. He received Pazopanib 800 mg in the first-line therapy and tolerated it without any side effects. At first, the therapy resulted in rapid clinical improvement, however, he died from severe tumor burden and DIC at the end of the second month of treatment. One RCC patient with low tumor burden received pazopanib treatment after three cycles of chemotherapy and then were followed up in the 11th month6. However, another patient with severe clinical manifestation of RCC was receiving anticoagulant therapy but died four weeks after her admission before she started receiving treatment for the disease5. According to a study on 1117 patients with solid tumors, those with overt DIC (9 months) had significantly lower survival rates than those with non-overt DIC (14 months) (p =0.005). This indicates that serious complications, such as DIC, have a great impact on cancer outcomes4.
Patients with cancer may sometimes present with venous thromboembolism or pulmonary embolism before the diagnosis of cancer. However, thrombotic complications of cancer are not limited to thrombosis but may manifest themselves with other signs of procoagulant state in its most fulminant form presenting as DIC17. The clinical manifestation of DIC in cancer may be thrombosis, bleeding, or the combination of the two1. Thrombotic microangiopathy may also occur18. Our patient was also admitted to the clinic due to bleeding and thrombosis, which are signs of a severe procoagulant state. Laboratory findings are necessary to confirm a diagnosis. Acute DIC almost always presents with thrombocytopenia and microangiopathic hemolytic anemia.
The treatment of underlying disease for DIC is the most effective approach in cancer patients. However, supportive therapy has also been used in combination with targeted therapy to prevent rapid exacerbation of coagulopathy17. Targeted therapy depends on the type of cancer. Some of the target therapies are cytotoxic chemotherapy, immunotherapy, molecularly targeted therapy, radiation therapy, endocrine therapy, and surgical therapy. Targeted therapy is the most important cancer treatment, and success in the treatment of primary disease results in withdrawal of DIC19. As for anticoagulant therapy, chemotherapy combined with low molecular weight heparin reduces the mortality rate in patients with solid tumors17. On the other hand, recombinant human soluble thrombomodulin (thrombomodulin alfa, TM-α) improves DIC scores and treats solid tumors, at least temporarily, and results in prolonged survival rate when the control of DIC and treatment of the underlying disease are compatible 20. Our patient also received transfusion support and low molecular weight heparin therapy until he received treatment for the disease.
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