Therapy management from the point of view of improving prognosis

Renal cell carcinoma is one of the common malignant tumors of the kidney, accounts for about 3% of all tumor cases, and the rate of new cases is increasing. In terms of drug treatment options, this tumor entity has undergone more rapid change in recent years than almost any other malignant disease. Meanwhile, the focus is not only on targeted therapy in advanced renal cell carcinoma, but also on combination treatments.

Every year, approximately 1060 people in Switzerland develop renal cancer (RCC) [1]. The majority of tumors histologically belong to the clear cell renal carcinomas, which – depending on the subtype – have a slightly better prognosis than non-clear cell renal cancer [2]. However, in the advanced stage, the prognosis is unfavorable for most affected individuals: three quarters of them have a moderate to high risk of the disease not stopping [3]. Numerous new approvals have significantly changed the therapeutic landscape for metastatic renal cell carcinoma. Targeted therapies were joined by immune checkpoint inhibitors, which can now be used in combination [4].

The main risk factors for developing RCC are smoking, hypertension, and obesity. Possible additional risk factors include terminal renal failure/acquired cystic kidney degeneration and occupational exposure to X-rays or halogenated hydrocarbons [5]. After the age of 50, the risk increases. Men are affected about twice as often as women. Since the disease is initially asymptomatic, it is often discovered by chance. The clinical triad of painless macrohematuria, flank pain, and palpable mass is often absent in clinical practice.

Classification and prognosis score

Classification is based on TNM and UICC criteria. The size and spread of the primary tumor, the involvement of lymph nodes and the presence of distant metastases are all relevant. However, compared to many other tumor entities, renal cell carcinoma is considered difficult to predict using the TNM system. Therefore, the Heng criteria and the Motzer or Memorial Sloan Kettering Cancer Center (MSKCC) score are more commonly used. Here, affected individuals are assigned to one of three risk groups with favorable, intermediate, or unfavorable risk profiles [5].

Therapy management up-to date

The choice of therapy depends on the spread of the tumor and whether metastases have already formed. In localized RCC, resection is the standard of care, with attempts now being made to preserve the healthy organ portions by nephron-sparing surgery without compromising oncologic radicality in terms of R0 resection. This is followed by immunotherapy. Immuno-oncologic therapies are nowadays an essential component of systemic therapy for renal cell carcinoma, along with targeted or anti-angiogenic therapies. However, more precise selection is still needed here to find the appropriate immunotherapy for the individual patient [6].

In first-line therapy of advanced and metastatic RCC, immuno-oncologic mono- and combination therapies represent the new standard. The basis of the combinations are inhibitors of the PD-1 or PD-L1 pathway. Possible combination partners include CTLA-4 inhibitors or TKIs such as cabozantinib. CTLA-4 inhibitors are also immuno-oncologically active. Classical chemotherapy is currently of no relevance in the treatment of metastatic renal cell carcinoma, as clear cell renal cell carcinoma in particular is almost completely resistant to the commonly used cytotoxic or cytostatic agents. The S3 guideline was updated accordingly in 2022. In all high-risk groups, a combination of nivolumab plus cabozantinib, pembrolizumab plus axitinib, or pembrolizumab plus lenvatinib should be used for first-line therapy of advanced or metastatic clear cell RCC. If this is not possible, avelumab and axitinib can be resorted to. For patients with intermediate or unfavorable risk, the combination ipilimumab plus nivolumab should be given [5,7].

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