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Objectives: To investigate the efficacy of pharmacotherapy for metastatic non‐clear cell renal cell carcinoma (nccRCC) in Japanese population. Methods: In this retrospective analysis, we compared the time to treatment failure (TTF) for molecular‐targeted agents as first‐line therapy, or nivolumab therapy as sequential therapy between ccRCC and nccRCC using the data of Japanese metastatic RCC patients registered in the Michinoku Japan Urological Cancer Study Group database. Results: In total, 511 cases of ccRCC and 77 cases of nccRCC were treated with pharmacotherapy. After excluding the patients who received cytokine therapy, chemotherapy, or others, there were 391 ccRCC patients and 60 nccRCC patients who were treated with tyrosine kinase inhibitors (TKIs), and 7 ccRCC patients and 7 nccRCC patients who were treated with mammalian‐target of rapamycin inhibitors (mTORIs). In addition, 132 ccRCC patients and 16 nccRCC patients received nivolumab. There was no significant difference in IMDC risk classification before first‐line therapy between ccRCC and nccRCC groups, or in each subgroup within the nccRCC group. TTF for TKIs (161 days, 95% CI: 75‐212 days) and mTORIs (21 days, 95% CI: 9‐31 days) didn't differ significantly between nccRCC and ccRCC groups (205 days, 95% CI: 174‐243 days and 33 days, 95% CI: 8‐113 days, respectively). TTF for TKIs was significantly longer than that for mTORIs in nccRCC group (p<0.01). There was no significant difference in TTF between the different TKIs in nccRCC group. In addition, no significant difference in TTF for nivolumab was seen between ccRCC and nccRCC groups. Conclusions: The results showed that the efficacy of molecular‐targeted agents as first‐line therapy was similar oncological outcomes between metastatic nccRCC and ccRCC in Japanese patients. TKIs may be more effective than mTORIs in metastatic nccRCC patients. Nivolumab administration might also be as effective in nccRCC patients as in ccRCC patients in Japanese population. [ABSTRACT FROM AUTHOR]

Background: This study is part of the SNPs in Nivolumab PD‐1 inhibitor for RCC (SNiP‐RCC). Here we aimed to reveal clinical factors for tumor response, progression, and survival in nivolumab for advanced clear cell renal cell carcinoma (RCC) in Japanese patients. Methods: We included patients from 23 institutions in Japan. We evaluated the objective response, radiographic progression‐free survival (PFS), overall survival (OS), and treatment‐related grade ≥ 3 (serious adverse events [SAEs]). Results: We included 222 patients. The median age was 69 years (interquartile range 62–74 years), and 71% of the patients were male. Pancreas metastasis, lung metastases, prior cytokine therapy, and SAEs, were associated with objective response. The median PFS was 18 months. Liver metastases (hazard ratio [HR], 1.61), age ≥ 75 (HR, 0.48), previous resection of primary sites (HR, 0.47), and SAEs (HR, 0.47) were independent prognostic factors for PFS. Karnofsky Performance Status <70 (HR, 2.90), high platelets (HR, 4.48), previous resection of primary sites (HR, 0.23), and pathological grade (HR, 0.19 for grade 2 and HR, 0.12 for grade 3) were independent prognostic factors for OS. SAEs were reported in 45 (20.3%) cases. In the group of patients with prior nephrectomy, SAEs were associated with objective response, PFS, and OS. Conclusion: The SNiP‐RCC study identified clinical parameters correlated with treatment outcomes in Japanese patients with priorly treated advanced clear cell RCC undergoing nivolumab monotherapy. [ABSTRACT FROM AUTHOR]

It remains unknown whether the early response to vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR‐TKI) management in malignancies links to long‐term survival. The objective of this study was to investigate the survival rates and predictive factors of early response in patients with metastatic renal cell carcinoma (mRCC) managed by VEGFR‐TKIs. From Jan. 2008 to Oct. 2018, 496 patients were treated with VEGFR‐TKIs as first‐line treatment at the eight Japanese hospitals (Michinoku RCC). Early cessation was defined as VEGFR‐TKIs being given up within 3 months after their initiation. The number of patients in early cessation VEGFR‐TKIs (Cohort I) was 173 (34.9%), and in long‐term use (Cohort II) was 323 (65.1%). The cancer‐specific survival (CSS) and overall survival (OS) were better in Cohort II. IMDC Poor‐risk was at risk of early cessation of a first‐line VEGFR‐TKI. Axitinib was the most preferred drug for long‐term treatment. On closer examination, both Cohort I and II were divided into two groups, the patients ceased VEGFR‐TKI due to adverse events (Group A [67 from Cohort I] and Group C [51 from Cohort II]) and disease progression (Group B [106 from Cohort I] and Group D [272 from Cohort II]). Despite that the cessation was adverse events, CSS and OS in Group A were worse than both Group C and D. Axitinib was administered with the safer profile. IMDC Poor risk was the risk factor for the early disease progression. Managing early adverse events may contribute to a better prognosis in mRCC patients treated VEGFR‐TKIs. [ABSTRACT FROM AUTHOR]

This letter, published in the journal Clinical & Experimental Nephrology, discusses the case of a 60-year-old man who underwent bilateral nephrectomy for renal cell carcinoma (RCC). The authors measured the levels of erythropoietin (EPO) before and after the surgery to examine the impact of nephrectomy on EPO production. They found that EPO levels declined sharply after the surgery and gradually increased over time, but were not sufficient to correct the patient's anemia. The authors discuss the potential use of erythropoiesis stimulating agents (ESA) and hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI) to address anemia in patients who have undergone nephrectomy. However, they note that the effects of HIF-PHI on malignant cells are not yet fully understood. [Extracted from the article]

Background: The aims of this study were to investigate prognosis and validate prognostic models [Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic Renal Cell Carcinoma Data Consortium (IMDC), and Japanese metastatic renal cancer (JMRC) models] in the targeted therapy era in Japanese patients with metastatic renal cell carcinoma. Methods: We retrospectively analyzed 692 patients who were diagnosed with mRCC from January 2008 to August 2018 in the Michinoku Japan Urological Cancer Study Group database. Nivolumab as sequential therapy was widely used. Other immune checkpoint inhibitors were excluded from this study. Results: The median overall survival (95% confident interval) in all, MSKCC favorable, intermediate, and poor risk patients was 41.0 months (33.9–46.8), not reached (63.5 to not estimable), 46.8 months (37.1–52.9), and 10.4 months (8.9–14.4), respectively. The median overall survival (95% confident interval) in IMDC favorable, intermediate, and poor risk patients was not reached (61.6 to not estimable), 47.4 months (41.4–56.5), and 11.5 (9.9–16.3), respectively. The c-index of the MSKCC, IMDC, and JMRC models calculated at mRCC diagnosis was 0.680, 0.689, and 0.700, respectively. No statistical differences were found in the c-index among the models. Conclusion: While the real-world overall survival in Japanese patients with mRCC in the targeted therapy era improved compared to that previously reported in the cytokine era, there was no clear difference in the survival of poor risk patients between these eras. There were no differences in the superiority among the models. [ABSTRACT FROM AUTHOR]

Correlation of PD-L1 tumor expression and treatment outcomes in patients with renal cell carcinoma receiving sunitinib or pazopanib: results from COMPARZ, a randomized controlled trial. Based on these results, PD-L1 expression on tumor cells is not widely used as a biomarker for anti-PD-1/PD-L1 therapy in RCC patients. Keywords: anti-PD-1/PD-L1 therapy; biomarker; renal cell carcinoma; PD-L1 expression; peripheral blood biomarkers EN anti-PD-1/PD-L1 therapy biomarker renal cell carcinoma PD-L1 expression peripheral blood biomarkers 667 669 3 07/05/22 20220701 NES 220701 1. Significance of PD-L1 expression on tumor as a biomarker Expression of PD-L1 on tumor cells facilitates cancer immune evasion. [Extracted from the article]

Although combination immune checkpoint inhibitor (immuno‐oncology [IO]) therapy is the first‐line treatment for metastatic renal cell carcinoma (mRCC), it mostly causes resistance and tumor regrowth. Therefore, an optimal second‐line therapy is necessary. Such therapy typically comprises vascular endothelial growth factor receptor‐tyrosine kinase inhibitors (VEGFR‐TKIs). This study was aimed at comparing the efficacy of two TKIs—axitinib and sunitinib—in mRCC patients. From January 2008 to October 2018, we registered 703 mRCC patients from 8 Japanese institutes. Of these, 408 patients received axitinib or sunitinib as the first‐line treatment. Thereafter, efficacy and survival rate were compared between the axitinib and sunitinib groups. To reduce the effects of selection bias and potential confounders, propensity score matching analysis was performed. Axitinib and sunitinib were administered in 274 and 134 patients, respectively. More than 25% of the patients received nivolumab sequence therapy. To calculate the propensity scores for each patient, we performed multivariate logistic regression analysis. The objective response rate, progression‐free survival (PFS), cause‐specific survival, and overall survival (OS) were significantly better in the axitinib group than in the sunitinib group. Furthermore, the OS was better in the nivolumab‐treated patients in the axitinib group. Axitinib showed higher efficacy and afforded greater survival benefits than did sunitinib when administered as first‐line therapy in mRCC patients. Thus, from among VEGFR‐TKIs, axitinib might be a possible option for application in the middle of IO drug‐based treatment sequences. [ABSTRACT FROM AUTHOR]

Objectives: To compare overall survival between patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy and those not treated by cytoreductive nephrectomy. Methods: We retrospectively evaluated 278 patients with metastatic renal cell carcinoma treated with first‐line tyrosine kinase inhibitors between January 2008 and November 2019. Patients were divided into two groups: a cytoreductive nephrectomy group (immediate or deferred cytoreductive nephrectomy) and a group who received systemic tyrosine kinase inhibitor therapies alone without cytoreductive nephrectomy (control group). Overall survival comparisons were made in all patients in the control versus the cytoreductive nephrectomy group, the control versus the immediate cytoreductive nephrectomy group, the control versus the deferred cytoreductive nephrectomy group, and the deferred cytoreductive nephrectomy versus the immediate cytoreductive nephrectomy group. Analyses were weighted using the propensity score‐based inverse probability of treatment weighting method to adjust for group imbalances. Results: The median (range) age of the patients was 65 (59–73) years. Of the 278 patients, 132 and 146 were in the control group and the cytoreductive nephrectomy (immediate, n = 107 and deferred, n = 39) group, respectively. A significant difference was noted between the control and cytoreductive nephrectomy groups in age, clinical stage, International Metastatic Renal Cell Carcinoma Database Consortium risk factors, and the number of metastatic sites. Inverse probability of treatment weighting‐adjusted Cox regression analysis showed a significant difference in overall survival between the control and the cytoreductive nephrectomy groups and between the control and the immediate or deferred cytoreductive nephrectomy groups. However, there was no significant difference in overall survival between the immediate and the deferred cytoreductive nephrectomy groups. Conclusions: Our findings suggest that metastatic renal cell carcinoma patients undergoing cytoreductive nephrectomy are more likely to have longer overall survival than those who receive tyrosine kinase inhibitor therapy only. [ABSTRACT FROM AUTHOR]

The phase 3 JAVELIN Renal 101 trial of avelumab + axitinib vs sunitinib in patients with treatment‐naive advanced renal cell carcinoma (RCC) demonstrated significantly improved progression‐free survival (PFS) and higher objective response rate (ORR) with the combination vs sunitinib. Japanese patients enrolled in the study (N = 67) were randomized to receive avelumab + axitinib (N = 33) or sunitinib (N = 34); 67% vs 59% had PD‐L1+ tumors (≥1% of immune cells) and 6%/64%/27% vs 6%/82%/12% had International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable/intermediate/poor risk status. In patients who received avelumab + axitinib vs sunitinib, median PFS (95% confidence interval [CI]) was not estimable (8.1 months, not estimable) vs 11.2 months (1.6 months, not estimable) (hazard ratio [HR], 0.49; 95% CI, 0.152, 1.563) in patients with PD‐L1+ tumors and 16.6 months (8.1 months, not estimable) vs 11.2 months (4.2 months, not estimable) (HR, 0.66; 95% CI, 0.296, 1.464) in patients irrespective of PD‐L1 expression. Median overall survival (OS) has not been reached in either arm in patients with PD‐L1+ tumors and irrespective of PD‐L1 expression. ORR (95% CI) was 60.6% (42.1%, 77.1%) vs 17.6% (6.8%, 34.5%) in patients irrespective of PD‐L1 expression. Common treatment‐emergent adverse events (all grade; grade ≥3) in each arm were hand‐foot syndrome (64%; 9% vs 71%; 9%), hypertension (55%; 30% vs 44%; 18%), hypothyroidism (55%; 0% vs 24%; 0%), dysgeusia (21%; 0% vs 56%; 0%) and platelet count decreased (3%; 0% vs 65%; 32%). Avelumab + axitinib was efficacious and tolerable in treatment‐naive Japanese patients with advanced RCC, which is consistent with results in the overall population. [ABSTRACT FROM AUTHOR]

Use of peptide‐based vaccines as therapeutics aims to elicit immune responses through antigenic epitopes derived from tumor antigens. Peptide‐based vaccines are easily synthesized and lack significant side‐effects when given in vivo. Peptide‐based vaccine therapy against several cancers including urological cancers has made progress for several decades, but there is no worldwide approved peptide vaccine. Peptide vaccines were also shown to induce a high frequency of immune response in patients accompanied by clinical efficacy. These data are discussed in light of the recent progression of immunotherapy caused by the addition of immune checkpoint inhibitors thus providing a general picture of the potential therapeutic efficacy of peptide‐based vaccines and their combination with other biological agents. In this review, we discuss the mechanism of the antitumor effect of peptide‐based vaccine therapy, development of our peptide vaccine, recent clinical trials using peptide vaccines for urological cancers, and perspectives of peptide‐based vaccine therapy. [ABSTRACT FROM AUTHOR]

Background: A high incidence of severe hematological adverse events during sunitinib treatment complicates decision making on dose and treatment cycle. We identified the characteristics of early-onset hematotoxicity of sunitinib in Japanese patients with renal cell carcinoma (RCC).Methods: Seventy-nine patients were treated with sunitinib as 6-week cycles of "4-week on 2-week off" schedule. To evaluate early-onset hematotoxicity, we compared patients with dose reduction during the first cycle (dose-reduced group, n = 57) and those who maintained the initial dose (dose-maintained group, n = 22). ABCG2 and FLT3 genotypes were analyzed for association between hematotoxicity and reported gene polymorphisms.Results: Mean relative dose intensity (RDI) was similar in the two groups during the first 2 weeks of dosing in the first cycle, but was significantly lower in the dose-reduced group during the last 2 weeks. Lymphocytopenia and thrombocytopenia were observed in the dose-reduced group within the first 2 weeks. Genetic analysis indicated a significantly higher frequency of FLT3 738 T/C polymorphism in the dose-reduced group, but no significant difference in the ABCG2 421 C/A polymorphism.Conclusions: This study showed a high incidence of sunitinib-induced hematotoxicity in Japanese patients with RCC, many of whom need dose adjustment during the first cycle. Further studies should verify whether dose adjustment based on early-onset thrombocytopenia prolongs sunitinib treatment. [ABSTRACT FROM AUTHOR]

Among patients in whom the T-cell response was analyzed, five patients showed a vaccine-induced T-cell response against at least one HLA class I-restricted TUMAP and two patients had T-cell responses to multiple TUMAPs. Although a phase III trial using IMA901 vaccine plus sunitinib compared to sunitinib monotherapy as first line treatment in patients with metastatic RCC has not shown survival benefit,[4] IMA901-specific CD8-positive T cell responses were recognized in some patients. Editorial Comment to Phase I/II study of multipeptide cancer vaccine IMA901 after single-dose cyclophosphamide in Japanese patients with advanced renal cell cancer with long-term follow up. [Extracted from the article]

Abstract: Here, we report a case of a 68‐year‐old woman with cT4N0M1 (liver invasion and multiple lung metastases) metastatic renal cell carcinoma. We could carry out less invasive nephrectomy with partial hepatectomy because nivolumab administration as second‐line therapy reduced the primary tumor remarkably. To the best of our knowledge, this is the first report of the use of nivolumab before carrying out surgery, and histological findings showed a pathological complete response. [ABSTRACT FROM AUTHOR]

A multicenter cooperative study was conducted to clarify the prognosis of Japanese patients with metastatic renal cell carcinoma in the era of molecular-targeted therapy and the clinical usefulness of the Japanese metastatic renal cancer ( JMRC) prognostic classification. Of 389 consecutive patients for whom treatment was started between 2008 and 2010 at 23 hospitals in Japan, 357 patients who received vascular endothelial growth factor receptor-tyrosine kinase inhibitor ( VEGFR- TKI) or cytokine as initial systemic therapy were the subject of the present study. Patients were classified into three prognostic groups according to the JMRC prognostic classification. The endpoints were progression-free survival ( PFS) and overall survival ( OS) after the start of the initial treatment. The median PFS and OS for the entire cohort of 357 patients were 9.1 and 27.2 months, respectively. VEGFR- TKI were selected for patients with multiple organ metastases, those with liver metastasis, and those with bone metastasis. The median PFS and OS were 11.0 and 23.2 months and 5.4 and 38.2 months in the VEGFR- TKI group and the cytokines group, respectively. The JMRC prognostic classification was useful as a prognostic model for PFS and OS (c-indexes: 0.613 and 0.630 in patients who initially received VEGFR- TKI and 0.647 and 0.642 in patients who received cytokines, respectively). The present study showed for the first time the prognosis of Japanese patients with metastatic renal cell carcinoma in the era of molecular-targeted therapy. The JMRC prognostic classification may be clinically useful as a prognostic model. [ABSTRACT FROM AUTHOR]

Remarkable advances have been made in medical practice in relation to renal cell carcinoma in recent years, and a large amount of new evidence has been accumulated. In keeping with the plan at the time the first version of the 'Evidence-Based Clinical Practice Guideline for Renal Cell Carcinoma' compiled by the Japanese Urological Association was published in 2007, the Japanese Urological Association has just published a revised 2011 version. The main revisions regard the selection of treatment methods according to prognostic factors, reconsideration of treatment methods for small-diameter renal cell carcinoma and selection criteria for medical treatment of advanced renal cell carcinoma, including selection of neoadjuvant treatment with molecular targeted medicines. This Guideline presents clinical practice methods that are thought to be the most standard methods in Japan at the present time. In this English translation of a shortened version of the original Guideline, we cited particularly important clinical questions and references. [ABSTRACT FROM AUTHOR]

The text of these guidelines was published for general clinicians, general urologists, and patients, with the aim of providing a system of effective and efficient clinical practices for managing renal cell carcinoma based on evidence-based medicine–intended techniques. The guidelines contain the answers to a total of 21 clinical questions (CQ) that were formulated under the headings of ‘risk factors and prophylaxis,’‘diagnosis,’‘surgical treatment and local treatment,’ and ‘systemic treatment,’ along with the recommendation grades and systems/algorithms for clinical practice based on structured abstracts prepared through critical reviews of the relevant published reports; the literature search was conducted using the key words for each CQ. An abridged edition of these guidelines can be found on the web pages of the Japan Society of Clinical Oncology and the Medical Information Network Distribution Service. [ABSTRACT FROM AUTHOR]

Objectives: To assess the safety and efficacy of combined therapy with interferon-alpha (INF-α) and active vitamin D3 for metastatic renal cell carcinoma (RCC). Methods: Sixteen patients with metastatic RCC were enrolled in this prospective study. All received oral alfacalcidol (1 µg once daily) and INF-α (Sumiferon; 3 million units, three times a week). The primary endpoint was the response rate (defined as complete + partial remission). Secondary endpoints were cancer-specific survival and toxicity. The median follow-up period was 17 months (range: 5–49 months). Results: The median age of the patients was 68 years (range: 41–73 years). The sites of metastases were: lung in 13 patients, bone in one, lung and bone in one, and lung, bone, and lymph nodes in one. Four patients (25%) had a partial response (PR), 10 patients (62.5%) showed no change (NC), and two patients (12.5%) had progressive disease (PD). The median cancer-specific survival time was 45 months. One patient had to discontinue vitamin D3 because of hypercalcemia. Kaplan-Meier survival analysis revealed that metastasis at the time of initial diagnosis and older than average age were significant predictors of poor survival ( P < 0.05). Conclusions: Combined treatment with INF-α and active vitamin D3 has shown to be safe and effective for metastatic RCC patients. [ABSTRACT FROM AUTHOR]

Purpose: The active form of vitamin D3, that is 1α,25-dihydroxyvitamin D3, binds with vitamin D receptor, which forms a complex with retinoid X receptors α, β and γ to manifest antitumor effects. We examined the expression of vitamin D receptor and retinoid X receptors in renal cell carcinoma and elucidated the prognostic significance of these receptors. Materials and Methods: We performed immunohistochemical examination of vitamin D receptor, and retinoid X receptors α, β and γ in nephrectomized specimens of 68 patients with renal cell carcinoma. We analyzed the correlation between the expression of these receptors and clinicopathological parameters or patient survival. Mean followup was 68.2 months. Results: No significant correlation was found between the expression of vitamin D receptor, retinoid X receptor α or β and clinicopathological parameters. In contrast, retinoid X receptor γ expression correlated significantly with tumor stage (p = 0.009) and distant metastasis (p = 0.005). The 5-year cancer specific survival rate was higher in patients with retinoid X receptor γ positive renal cell carcinoma than those with retinoid X receptor γ negative renal cell carcinoma (79.3% vs 40.0%, p <0.05). Cox regression analysis revealed that retinoid X receptor γ expression, tumor status and lymph node status were significant independent prognostic factors in patients with renal cell carcinoma (p <0.05). A significant correlation was observed between the expression of retinoid X receptor γ and tumor stage, distant metastasis or the 5-year cancer specific survival rate. Furthermore, retinoid X receptor γ expression was an independent prognostic factor in patients with renal cell carcinoma. Conclusions: Our observations suggest that alterations of vitamin D receptor and retinoid X receptor expression may be involved in renal carcinogenesis and retinoid X receptor γ expression may be a useful prognostic marker in patients with renal cell carcinoma. [Copyright &y& Elsevier]

Aim: Biological and epidemiologic data suggest that 1 alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3) levels may influence development of renal cell carcinoma. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of 1,25(OH)2D3 and additionally interacts with other cell signaling pathways that influence cancer progression. VDR gene polymorphisms may play an important role in risk of incidence for various malignant tumors. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of renal cell carcinoma (RCC) in a Japanese population. Methods: To analyze risk of RCC depending on VDR polymorphism, a case–control association study was performed. The VDR gene polymorphisms at three locations, BsmI, ApaI and TaqI, were genotyped in 135 RCC patients and 150 controls in a Japanese population. Logistic regression models were used to assess the genetic effects on prognosis. Results: Significant differences in the ApaI genotype were observed between RCC patients and controls (χ2 = 6.90, P = 0.032). No statistical significant difference was found in the BsmI and TaqI polymorphisms. The frequency of the AA genotype in the ApaI polymorphism was significantly higher in the RCC patients than in the controls (odds ratio, 2.59; 95% confidence intervals, 1.21–5.55; P = 0.012). Multivariate regression analysis showed that the AA genotype was an independent prognostic factor for cause-specific survival (relative risk 3.3; P = 0.038). Conclusion: The AA genotype at the ApaI site of the VDR gene may be a risk of incidence and poor prognosis factor for RCC in the Japanese population. Additional studies with a large sample size and investigation of the functional significance of the ApaI polymorphism in RCC cells are warranted. [ABSTRACT FROM AUTHOR]

Abbreviations & Acronyms anova analysis of variance CR complete response CT computed tomography ICI immune checkpoint inhibitor KPS Karnofsky Performance Status LMR lymphocyte-to-monocyte ratio mRCC metastatic renal cell carcinoma NLR neutrophil-to-lymphocyte ratio ORR objective response rate OS overall survival PD progressive disease PFS progression-free survival PLR platelet-to-lymphocyte ratio PR partial response RECIST Response Evaluation Criteria in Solid Tumors ROC receiver operating characteristic SD stable disease The therapeutic strategy for mRCC has expanded in recent years. Despite these limitations, the NLR is a readily available biomarker that provides additional information to predict the nivolumab response and helps in the consideration of sequence therapy in mRCC patients. [Extracted from the article]

Background: Reduced port laparoscopic surgery (RPLS) is comparable to conventional multiport laparoscopic surgery and has the potential to provide improved cosmesis and decreased pain; as such, it satisfies a growing demand for less invasive surgical procedures. Moreover, a zigzag incision of the umbilicus results in a less visible scar in plastic surgery. Here we report a series of two cases with bilateral organ tumors treated by single-stage RPLS using a combination of a transumbilical approach and a zigzag incision.Case Presentation: Case 1: A 63-year-old man was diagnosed with right renal cell carcinoma (RCC) (clear cell carcinoma, pT1a, venous invasion (-)) and a splenic tumor (cavernous hemangioma). Case 2: An 84-year-old woman was diagnosed with concurrent left RCC (clear cell carcinoma, pT1b, 65 × 65 mm, venous invasion (+)) and ascending colon cancer (adenocarcinoma pT3 with no nodal involvement (0/48)). The perioperative course was uneventful in both cases. However, an additional incision was required in Case 2 for specimen excision. Therefore, the scars were more obvious in Case 2 than in Case 1.Conclusions: Although more cases are required to evaluate the superiority of this technique, this novel procedure could be considered for patients with bilateral lesions. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case of a metastatic renal cell carcinoma (mRCC) patient who achieved a complete response (CR) to everolimus.

The author comments on a study related to interleukin-16 (IL-16) polymorphism with risk of renal cell carcinoma (RCC) in China, published within this issue. The study reports the involvement of polymorphism for developing RCC has been revealed in Chinese population. According to the author single-nucleotide polymorphism also controls response toward medications. The author further mentions that if the IL-16 polymorphism study is confirmed, it might offer cancer prevention and treatment for RCC.

• Response patterns to nivolumab–ipilimumab therapy in advanced renal cell carcinoma. • Lung metastasis exhibited early response to the combination therapy. • Lung metastasis related positively to progression-free survival and overall response. This study aimed to identify patterns of early response to nivolumab and ipilimumab combination therapy (Nivo+Ipi) in primary and metastatic sites of advanced renal cell carcinoma (RCC). RCC patients treated with Nivo+Ipi or tyrosine-kinase inhibitors (TKIs) as first-line therapy were included. To exclude selection bias due to patient characteristics, baseline clinical data was adjusted by inverse probability of treatment weighting (IPTW). Overall response rate (ORR) and lesional response rates (LRR) in primary and metastatic sites were determined by measuring tumor diameters on serial CT images according to Response Evaluation Criteria in Solid Tumors, version 1.1. 33 patients were treated with Nivo+Ipi and 39 with TKIs as first-line therapy. After IPTW-adjusted analysis, ORR during the first 24 weeks of treatment was significantly higher in Nivo+Ipi group than in TKIs group (45.5% versus 21.7%, p < 0.01). LRR of the primary tumor tended to be higher in Nivo+Ipi group than in TKI group (14.8% versus 4.4%, p = 0.06). Mean LRR of all metastatic sites was not significantly different between the two groups, but tumor shrinkage rate of lung metastasis was significantly higher in Nivo+Ipi group than in TKIs group (68.5% versus −12.7%, p < 0.01). Univariate and multivariate analyses identified lung metastasis as the independent factor associated with prolonged progression-free survival and with higher ORR. Our study found that lung metastasis of advanced RCC exhibited early response to Nivo+Ipi therapy. Further studies are warranted to verify whether site-specific early response predicts overall survival benefit in advanced RCC patients treated with Nivo+Ipi. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate the utility of the scoring system of the Registry for Metastatic Renal Cell Carcinoma (REMARCC) model on the overall survival (OS) of patients undergoing cytoreductive nephrectomy (CN).Methods: A total of 278 patients with primary metastatic renal cell carcinoma (mRCC) treated with first-line tyrosine kinase inhibitors (TKIs) between January 2008 and November 2019 were identified. The c-index and net benefit between the REMARCC score were compared with the International mRCC Database Consortium (IMDC) score in patients with CN (CN group, n = 146). The effect of the REMARCC score on OS was compared between the CN group and patients without CN (non-CN group, n = 132) using Cox regression analysis under the propensity score-based inverse probability of treatment weighting (IPTW) method to adjust for group imbalances.Results: Of the 146 patients with CN, the c-index of the REMARCC model (0.60) was higher than the IMDC model (0.54). The decision curve analysis showed the advantage of REMARCC model predicting OS compared with the IMDC model. OS was significantly longer in the REMARCC low-score (0-2) than that in the high-score (3-6) among the patients with CN. IPTW-adjusted Cox regression analyses showed that OS was significantly longer in the CN group than that in the non-CN group among the patients with REMARCC low-score but was not significantly different between the groups among the patients with REMARCC high-score.Conclusions: The REMARCC score may be active for selecting the CN candidate in patients treated with TKIs. [ABSTRACT FROM AUTHOR]