Background Immune checkpoint inhibitors cause various immune-related adverse events. The present study examined the association between the incidence of immune-related adverse events and survival outcomes in patients treated with nivolumab plus ipilimumab for patients with advanced renal cell carcinoma. In addition, we compared the effect of adverse event profiles on survival for patients receiving nivolumab plus ipilimumab. Methods A total of 35 patients with advanced renal cell carcinoma who were treated with nivolumab plus ipilimumab from August 2018 to August 2021 were retrospectively reviewed and analyzed. Cox proportional hazards models were used for univariate and multivariate analyses, and hazard ratio and 95% confidence intervals were calculated. Results Of the 35 patients, 22 (62.9%) experienced immune-related adverse events. The median progression-free survival (P = 0.0012) and overall survival (P = 0.0147) were significantly longer in patients with immune-related adverse events than in those without immune-related adverse events. Multivariate analysis showed that the incidence of immune-related adverse events was an independent factor for progression-free survival (hazard ratio = 4.940, 95% confidence interval: 1.558–15.664, P = 0.0067). Skin reaction was a positive predictive immune-related adverse events for progression-free survival (hazard ratio = 9.322, 95% confidence interval: 1.954–44.475, P = 0.0051). Conclusion Patients with advanced renal cell carcinoma with immune-related adverse events had superior clinical outcomes of nivolumab plus ipilimumab treatment than those without immune-related adverse events. Skin immune-related adverse events may be effective biomarkers in patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab.

Spontaneous regression of metastatic renal cell carcinoma (RCC) is rare, but well-documented in clear cell RCC. However, there are no reports on spontaneous regression of unclassified RCC. Since the radiological findings of pulmonary infarcts and inflammatory pseudotumors are similar to those of metastases from RCC, a definitive diagnosis is difficult without performing a histological examination. A 56-year-old woman underwent medical examination by a physician. An abdominal computed tomography (CT) scan revealed a 22-mm mass with a cystic area in the right kidney, as well as multiple enlarged lymph nodes in the common iliac, external iliac and groin areas, bilaterally. A chest CT revealed multiple pulmonary nodules bilaterally, the largest measuring 15 mm. Since the right renal tumor was suspected to be an RCC, laparoscopic partial nephrectomy was performed. The final pathological diagnosis of the renal tumor was unclassified RCC. One month following surgery, a CT scan revealed spontaneous regression of the pulmonary nodules. We herein present a rare case of spontaneous regression of pulmonary nodules in a patient with unclassified RCC following laparoscopic partial nephrectomy. To the best of our knowledge, this is the first case of spontaneous regression in unclassified RCC.

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Summary:Since the introduction of targeted therapy, treatment of metastatic renal cell carcinoma (RCC) has undergone dramatic changes. Responses to targeted therapy within the primary tumor and metastatic lesions are novel findings not seen with immunotherapeutic-based strategies. We report here a case of T4 RCC in which cytoreductive nephrectomy became possible after a neoadjuvant targeted therapy using sunitinib. Our experience with the present case suggests that targeted therapy in the neoadjuvant setting may have a variety of potential applications. Further investigations should be encouraged.

Abstract. The aim of the present study was to investigate the prognostic factors for patients with primary unresectable renal cell carcinoma (RCC) with synchronous distant metastasis receiving molecularly targeted therapies. A total of 26 patients with primary unresectable RCC with synchronous distant metastasis underwent molecularly targeted therapies at the Kurume University Hospital (Kurume, Japan) between March 2008 and March 2016. Early primary renal tumor response was evaluated at 8-12 weeks after the introduction of molecularly targeted therapy and a 10% decrease in the diameter of primary renal tumor was used as the cut-off value. The median overall survival from the initiation of first-line molecularly targeted therapy was 18.3 months. Univariate analyses for various factors identified early primary renal tumor response (P=0.0004) and best response to first-line treatment (P=0.0002) as prognostic variables. Multivariate analyses also identified early primary renal tumor response (P=0.0099) and best response to first-line treatment (P= 0.0054) as independent prognostic factors. A comparison of clinical characteristics between the group with ≥10% shrinkage and the group with disease progression or <10% shrinkage revealed that the number of metastatic sites and pretreatment monocyte-to-lymphocyte ratio tended to be predictive factors for primary renal tumor response. These results suggest that early primary renal tumor shrinkage is highly variable for patients with primary unresectable RCC with synchronous distant metastasis receiving molecularly targeted therapies.