Renal cell carcinoma (RCC) is a common urinary system malignancy, with approximately 30% of patients presenting with distant metastasis at diagnosis or developing it post-surgery. Given RCC's insensitivity to conventional chemo-radiotherapy, molecular targeted therapies like sunitinib (a multi-targeted tyrosine kinase inhibitor) have become standard treatments. However, drug resistance remains a challenge. Transarterial chemoembolization (TACE), initially used for hepatocellular carcinoma, involves injecting chemotherapeutic agents and embolic agents into the tumor to induce apoptosis and ischemic necrosis. This study investigated whether combining TACE with sunitinib improves outcomes compared to sunitinib alone in patients with unresectable advanced RCC. The hypothesis was that the combination therapy would offer synergistic effects, leading to improved efficacy and manageable side effects.

The literature highlights the limitations of conventional treatments for advanced RCC, emphasizing the role of targeted therapies such as sunitinib, sorafenib, and pazopanib. While these agents improve patient outcomes, drug resistance remains a significant hurdle. Immunotherapy has emerged as a promising treatment option, with studies like CheckMate 214 demonstrating superior efficacy of nivolumab plus ipilimumab compared to sunitinib. Studies have also explored the role of cytoreductive nephrectomy combined with immunotherapy. TACE has shown promise in various cancers, including HCC, but its application in RCC has been less explored. Preoperative combined transarterial embolization (TAE) has been shown to reduce intraoperative bleeding. While some studies have investigated TACE alone in RCC, the combination with targeted therapy like sunitinib has not been thoroughly studied.

This retrospective study analyzed 98 patients with unresectable advanced RCC treated at Union Hospital between January 2015 and December 2018. Patients were divided into two groups: TACE + sunitinib (n=47) and sunitinib alone (n=51). Inclusion criteria included pathologically confirmed RCC, age 18-75 years, unresectable disease, acceptable liver and renal function, and adequate blood counts. Exclusion criteria included prior cancer-related therapies and allergies to contrast agents or sunitinib. TACE involved superselective catheterization of the renal arteries, injection of lipiodol + doxorubicin emulsion, and gelatin sponge particle embolization. Sunitinib was administered orally at 50 mg daily, following a 4-week on/2-week off regimen, with dose adjustments based on adverse events. Tumor response was assessed using modified RECIST (mRECIST) criteria after 3 months. Primary endpoints were OS and PFS. Secondary endpoints included ORR, DCR, changes in liver/renal function and blood counts, and adverse events using CTCAE 5.0. Statistical analysis used SPSS software, including chi-square tests, t-tests, Kaplan-Meier curves, and the Log-Rank test.

Baseline characteristics were comparable between the two groups. The TACE + sunitinib group demonstrated a significantly higher ORR (66.0% vs. 39.2%, p=0.009) and DCR (85.1% vs. 66.7%, p=0.038) compared to the sunitinib-only group. Median PFS was significantly longer in the TACE + sunitinib group (15.6 months vs. 10.9 months, p<0.001), as was median OS (35.0 months vs. 25.7 months, p<0.001). The TACE + sunitinib group had a significantly higher incidence of abdominal pain (55.3% vs. 13.7%, p<0.05), fever (61.7% vs. 7.8%, p<0.05), and vomiting (40.4% vs. 19.6%, p<0.05), consistent with post-embolization syndrome. There was no significant difference in other adverse events between the groups. Post-treatment albumin levels were significantly higher in the TACE + sunitinib group (35.76 ± 5.41 g/L vs. 33.37 ± 3.05 g/L, p=0.008), and WBC counts were significantly higher in the TACE + sunitinib group (6.92 ± 0.72 G/L vs. 3.52 ± 0.73 G/L, p<0.001).

The results support the hypothesis that combining TACE with sunitinib enhances treatment efficacy for unresectable advanced RCC. The significant improvements in ORR, DCR, PFS, and OS in the combination group suggest a synergistic effect. The mechanistic explanation for this may be related to TACE's ability to rapidly reduce tumor burden, thereby improving the efficacy of sunitinib by mitigating the effects of tumor-produced pro-angiogenic factors. The increased incidence of post-embolization syndrome in the combination group is expected given the nature of the procedure; however, the manageable nature of these side effects and the absence of significant differences in other sunitinib-related adverse events indicate a favorable safety profile. These findings align with studies showing similar benefits of combining TACE with targeted therapies in other cancers like HCC.

This study demonstrates that combining TACE with sunitinib is a safe and effective strategy for treating unresectable advanced RCC, leading to superior efficacy and improved survival outcomes compared to sunitinib alone. While post-embolization syndrome is a common side effect, it's manageable. Future research should focus on larger, prospective, multicenter studies to validate these findings and explore optimal treatment strategies, including potential modifications to the TACE protocol or sunitinib regimen to minimize side effects.

This study's limitations include its retrospective nature, single-center design, and relatively small sample size. The retrospective design increases the risk of bias and limits the generalizability of the results. A larger, prospective, multicenter study is necessary to confirm these findings and assess the long-term benefits of this combination therapy.