Efficacy and safety analysis of TACE + sunitinib vs. sunitinib in the treatment of unresectable advanced renal cell carcinoma: a retrospective study

Renal cell carcinoma (RCC) accounts for 80–90% of renal malignancies and is the third most common urinary system tumor. A substantial proportion of patients present with or develop metastases, and RCC is largely insensitive to traditional chemoradiotherapy. Systemic therapy with targeted drugs (e.g., sunitinib) and immunotherapy has improved outcomes but resistance and progression remain challenges. Transarterial chemoembolization (TACE), widely used in hepatocellular carcinoma and explored in RCC, can reduce tumor burden by delivering high local concentrations of chemotherapy and embolizing tumor vasculature. This study investigates whether combining TACE with the tyrosine kinase inhibitor sunitinib improves efficacy and maintains safety compared with sunitinib alone in unresectable advanced RCC.

Prior to targeted therapies, cytokine-based immunotherapy yielded limited benefit in advanced RCC. Sunitinib, a multi-target TKI (VEGFR, PDGFR, c-KIT, FLT-3), is an established first-line option with real-world mPFS ~7.5–11 months and mOS up to 31.5 months. Immune checkpoint inhibitors (e.g., nivolumab plus ipilimumab) have shown superiority to sunitinib in certain populations. TACE/TAE in RCC has been reported to palliate symptoms (pain, hematuria) and reduce tumor burden; various embolic/chemo agents (ethanol, mitomycin, doxorubicin) have been used. In HCC, combining TACE with TKIs improves outcomes by counteracting post-embolization hypoxia-induced proangiogenic signaling (elevated HIF/VEGF/PDGF). This mechanistic rationale supports evaluating TACE combined with sunitinib in RCC, though data have been limited.

Design: Single-center retrospective cohort study. Setting: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Period: January 2015–December 2018. Participants: 98 patients with unresectable advanced RCC. Inclusion criteria: pathologically confirmed RCC; age 18–75 years; venous invasion or distant metastasis precluding surgery; Child-Pugh A–B; ECOG 0–2; normal renal, cardiac, and coagulation function; WBC ≥3.5 G/L, PLT ≥100 G/L, Hb ≥100 g/L; complete follow-up data. Exclusion: prior tumor-related treatments; allergy to iodine contrast or sunitinib. Groups: TACE + sunitinib (N = 47) vs. sunitinib alone (N = 51). Baseline variables included demographics, pathology, venous invasion, metastasis, IMDC risk, liver and renal function, and hematology. Interventions: TACE technique—femoral access (Seldinger), 5F sheath; 5F catheter (Yashiro) for renal arteriography (including accessory/lumbar arteries if needed) to identify tumor feeders; 2.7F microcatheter for superselective cannulation; intra-arterial chemoembolization with lipiodol–doxorubicin emulsion (30–50 mg doxorubicin) followed by gelatin sponge particles to endpoint of stasis. If arteriovenous fistula present, superselective embolization with PVA particles prior to chemoembolization. Post-procedure care included enhanced CT/MRI every 3–6 months; repeat TACE as indicated. Sunitinib dosing: 50 mg orally once daily, 4/2 schedule (4 weeks on, 2 weeks off); dose halved for grade 3–4 adverse events. Outcomes: Primary—overall survival (OS) and progression-free survival (PFS). Secondary—tumor response by mRECIST (CR, PR, SD, PD); objective response rate (ORR = CR + PR) and disease control rate (DCR = CR + PR + SD); changes in liver/renal function, ECOG, blood counts; treatment-related adverse events (AEs) graded by CTCAE v5.0. Statistics: SPSS v24.0; categorical data as n (%), Pearson chi-square or Fisher’s exact; continuous data as mean ± SD, t-tests; Kaplan–Meier for OS/PFS with log-rank tests. Significance threshold P < 0.05.

- Tumor response (mRECIST): - TACE + sunitinib (N=47): CR 8.5% (4), PR 57.5% (27), SD 19.1% (9), PD 14.9% (7) - Sunitinib (N=51): CR 0% (0), PR 39.2% (20), SD 27.5% (14), PD 33.3% (17) - Between-group difference: P = 0.017 - ORR: 66.0% vs. 39.2% (P = 0.009) - DCR: 85.1% vs. 66.7% (P = 0.038) - Survival: - Median PFS: 15.6 vs. 10.9 months (P < 0.001) - Median OS: 35.0 vs. 25.7 months (P < 0.001) - Safety and laboratory findings: - Higher incidence of post-embolization symptoms with TACE + sunitinib: abdominal pain 55.3% vs. 13.7%; fever 61.7% vs. 7.8%; vomiting 40.4% vs. 19.6% (all P < 0.05) - No significant between-group differences in fatigue, anorexia, hypertension, hand–foot syndrome, diarrhea, rash; dose reductions: 8.5% vs. 5.9% - Post-treatment albumin: 35.76 ± 5.41 vs. 33.37 ± 3.05 g/L (P = 0.008); WBC: 6.92 ± 0.72 vs. 3.52 ± 0.73 G/L (P < 0.001) - Within-group changes: both groups had increased bilirubin, BUN, Cr and decreased GFR post-treatment; TACE group had increased WBC and decreased RBC/PLT; sunitinib group had decreased albumin/WBC/RBC/PLT - Technical success of TACE: 100%

Combining TACE with sunitinib significantly improved tumor response rates and prolonged PFS and OS compared with sunitinib alone, addressing the need to enhance outcomes in unresectable advanced RCC. Mechanistically, TACE induces tumor ischemia and hypoxia, which increases HIF activity and pro-angiogenic factors (e.g., VEGF, PDGF). Sunitinib inhibits VEGFR/PDGFR and related pathways, potentially mitigating post-embolization proangiogenic escape and enhancing cytoreduction achieved by TACE. The safety profile was acceptable; the higher rates of abdominal pain, fever, and vomiting in the combination group are consistent with post-embolization syndrome and were manageable. No significant increase in typical sunitinib-related AEs was observed. Laboratory changes were largely consistent with treatment effects and disease burden; ECOG scores did not differ between groups after treatment. These findings support TACE plus sunitinib as a complementary strategy to reduce tumor burden and improve survival in advanced RCC.

In unresectable advanced RCC, TACE combined with sunitinib yielded superior ORR, DCR, PFS (15.6 months), and OS (35.0 months) compared with sunitinib alone, without increasing sunitinib-related toxicity. The combination appears safe and effective, likely due to mechanistic synergy between embolization-induced cytoreduction and antiangiogenic therapy. Future multicenter, prospective studies with larger cohorts are warranted to confirm efficacy, refine patient selection, and optimize treatment sequencing and dosing.

Single-center, retrospective design with a limited sample size may introduce selection bias and limit generalizability. Lack of randomization and potential confounders (e.g., unmeasured disease characteristics, timing/number of TACE sessions) could affect outcomes. The study did not compare against contemporary immunotherapy-based regimens.