Renal cell carcinoma (RCC) is among the most common cancers of the genitourinary system. Once RCC has progressed to a high tumor stage, surgery is no longer the optimal option, and treatment with drugs is more suitable. However, a proportion of patients with advanced RCC (aRCC) experience accelerated progression following targeted therapy or immunotherapy, a condition known as hyperprogressive disease (HPD). There is a growing body of literature that recognizes the importance of HPD. In the present review, thousands of studies that describe a variety of treatments for aRCC were identified in PubMed, Web of Science, and Cochrane Library and analyzed to establish the severity of clinical outcomes. Therefore, we managed to perform a review related to HPD of aRCC in these databases. It was found that 7~74% of patients advanced into progressive disease, 0~45% of patients died during post-treatment assessment, possibly due to fatal HPD. However, risk factors, mechanisms, and predictive factors are still not entirely clear. It is suggested that combination therapies might play a pivotal role in preventing HPD. Additional light needs to be shed on customization of therapies for aRCC after more data is collected and analyzed for HPD.
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