Association of lung immune prognostic index with survival outcomes in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

OBJECTIVE: Lung immune prognostic index is based on derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase level. Lung immune prognostic index has reported association with survival outcomes in patients with various malignancies undergoing treatment with immune checkpoint inhibitors. However, the prognostic impact of pre-treatment lung immune prognostic index in patients with metastatic renal cell carcinoma receiving nivolumab plus ipilimumab treatment remains unclear. This study examines the association between lung immune prognostic index and outcomes in this setting. METHODS: We retrospectively evaluated 156 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab at eight institutions. We assessed the associations between pre-treatment lung immune prognostic index and survival outcomes including progression-free survival, second progression-free survival (PFS2), cancer-specific survival and overall survival. RESULTS: Patients were classified into good (n = 84, 54%), intermediate (n = 52, 33%) and poor (n = 20, 13%) lung immune prognostic index groups. Progression-free survival did not significantly differ between lung immune prognostic index groups, but there was significant difference in PFS2, cancer-specific survival and overall survival. In multivariable Cox proportional hazard analyses, high pre-treatment lung immune prognostic index was a significant predictor of poor PFS2 (vs. good group, intermediate group: P = 0.01 and poor group: P = 0.04) and poor overall survival (vs. good group, intermediate group: P = 0.01 and poor group: P < 0.01). Moreover, the patients with poor lung immune prognostic index had significantly poorer cancer-specific survival than those with good LIPI (P < 0.01). CONCLUSIONS: High pre-treatment LIPI is suggested by our results to be a significant independent predictor of poor prognosis in patients receiving nivolumab plus ipilimumab for metastatic renal cell carcinoma.

Real-world analysis of metastatic prostate cancer demonstrates increased frequency of PSA-imaging discordance with visceral metastases and upfront ARAT/docetaxel therapy.

BACKGROUND: The objective of this study was to evaluate the background and treatment course of patients with metastatic prostate cancer (PC), with a particular focus on radiographic progression in the absence of prostate-specific antigen (PSA) progression. METHODS: The study population consisted of 229 patients with metastatic hormone-sensitive PC (HSPC), who received prostate biopsy and androgen deprivation therapy at Kobe University Hospital between January 2008 and June 2022. Clinical characteristics were retrospectively evaluated using medical records. PSA progression-free status was defined as ≤1.05 times greater than that from 3 months before. Multivariate analyses were performed using the Cox proportional hazards regression model to identify parameters associated with time to progression on imaging without PSA elevation. RESULTS: A total of 227 patients with metastatic HSPC without neuroendocrine PC were identified. The median follow-up period was 38.0 months, with a median overall survival of 94.9 months. Six patients exhibited disease progression on imaging without PSA elevation during HSPC treatment, three during first-line castration-resistant PC (CRPC) treatment, and two during late-line CRPC treatment. The rate of disease progression without PSA elevation at 3 years after treatment initiation was 7.4%. Multivariate analysis revealed that organ metastases and upfront treatment with docetaxel or androgen receptor axis-targeted therapy were independent prognostic factors for imaging progression without PSA elevation. CONCLUSIONS: Disease progression on imaging without PSA elevation occurred not only during HSPC treatment and first-line CRPC treatment, but also during late-line CRPC treatment. Patients with visceral metastases or those treated with upfront androgen receptor axis-targeted or docetaxel may be more prone to such progression.

Bioabsorbable zinc alloys for use in urological surgery.

PURPOSE: Non-absorbable clips are widely used in urologic surgery and they may come in contact with an open urinary tract intraoperatively. As a result, stray clips in the urinary tract and associated intractable infections have been reported. We developed a bioabsorbable metal and evaluated whether it would dissolve if it strayed into the urinary tract. METHODS: We prepared four types of alloys mainly comprising zinc (Zn) with small amounts of magnesium (Mg) and strontium (Sr), and the biological effects, degradability, strength, and ductility were investigated. Each alloy was implanted in the bladder of five rats for 4, 8, and 12 weeks. The alloys were removed and evaluated for degradability, stone adhesion, and tissue changes. The Zn-Mg-Sr alloy had degradability and no stone adhesion in the rat experiments, and it was implanted in the bladders of five pigs for 24 weeks. The Mg and Zn levels in the blood were measured, and staple changes were confirmed by cystoscopy. RESULTS: Zn-Mg-Sr alloys showed the best degradability of 6.51% at 12 weeks. In pig experiments, the degradation rate was 3.72% at 24 weeks. None of the pigs had changes in the Zn or Mg concentrations in the blood. Overall, the bladder incision was healed and the gross pathology showed wound healing. CONCLUSIONS: The Zn-Mg-Sr alloys were safely used in animal experiments. Furthermore, the alloys are easy to process and can be formed into various shapes, such as staples, making them useful in robotic surgery.

Treatment outcome after sequential chemotherapy with cisplatin-etoposide, amrubicin and nogitecan in patients with treatment-related pure small-cell neuroendocrine prostate cancer.

OBJECTIVE: This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer. METHODS: We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival. RESULTS: The median cancer-specific survival after diagnosis for all patients was 22.4 months (range 1.3-33.4 months). The median progression-free survival was 9.3 months after first-line etoposide plus cisplatin (or carboplatin) treatment (n = 13); 4.2 months after second-line amrubicin treatment (n = 4); and >15 months after third-line nogitecan treatment (n = 2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2 months, and that of the (+) group was 5.3 months (P = 0.015, hazard ratio = 11.6, 95% confidence interval = 1.01 - 133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis. CONCLUSION: Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.

Avelumab plus Axitinib for the Treatment of Patients with End-Stage Renal Disease Undergoing Dialysis: A Retrospective Case Series and Literature Review.

Combination therapies of an immune checkpoint inhibitor and a molecular targeted agent are widely accepted as an appropriate initial systemic therapy for metastatic renal cell carcinoma (RCC), but there is little published evidence regarding the efficacy of this approach in patients with end-stage renal disease (ESRD). Here, we report three patients who were undergoing hemodialysis for ESRD whose metastatic RCC was successfully treated using avelumab plus axitinib. The patients were a 67-year-old man with swollen lymph nodes, a 65-year-old man with pleural dissemination, and a 71-year-old man with lung nodules and an infra-diaphragmatic nodule. They were administered a combination of avelumab plus axitinib as their initial systemic therapy following definitive surgical therapy. The best response of three patients was graded as partial response. No severe adverse events were identified. This is the first report of the use of combination therapy consisting of avelumab plus axitinib in patients with ESRD undergoing hemodialysis. We found that this combination was useful in such patients.

Impact of cytoreductive nephrectomy prior to combination therapy of ipilimumab plus nivolumab in metastatic renal cell carcinoma.

OBJECTIVES: The efficacy of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs) has been suggested in the real-world setting. We retrospectively examined the efficacy of CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC. METHODS: Synchronous mRCC patients who received nivolumab plus ipilimumab at Kobe University Hospital or five affiliated hospitals between October 2018 and December 2021 were included in this study. We compared the outcomes of objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) between patients with CN prior to systemic therapy and without CN. In addition, patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment. RESULTS: Twenty-one patients received CN prior to nivolumab plus ipilimumab (Prior CN) and 33 received nivolumab plus ipilimumab alone (Without CN). PFS of the Prior CN group was 10.8 months (95%CI 5.5-NR) and 3.4 months (95%CI 2.0-5.9) for the Without CN group (p = 0.0158). OS of Prior CN was 38.4 months (95%CI NR-NR) and 12.6 months (95%CI 4.2-30.8) for Without CN (p = 0.0024). Univariate and multivariate analyses identified prior CN as a significant prognostic indicator for PFS and OS. Moreover, propensity score matching analysis showed significant improvements in PFS and OS in Prior CN. CONCLUSIONS: Patients who underwent CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC had a better prognosis than patients treated with nivolumab plus ipilimumab alone. These results suggest the efficacy of prior CN for synchronous mRCC with ICI combination therapy.

Efficacy and safety of pembrolizumab and axitinib as first-line treatment for patients with advanced renal cell carcinoma: Real-world experience in Japan.

OBJECTIVES: The objective of this study was to assess the clinical outcomes following combined treatment with pembrolizumab and axitinib as first-line therapy for patients with advanced RCC. METHODS: This study retrospectively included 47 consecutive Japanese patients who were diagnosed with advanced RCC and subsequently received pembrolizumab and axitinib between February 2020 and January 2022. Efficacy and safety of this combined therapy in these patients were comprehensively investigated. RESULTS: The 47 included patients were classified into the following 3 groups by the IMDC system: favorable, 7 (14.9%); intermediate, 24 (51.1%) and poor, 16 (34.0%). Responses to this combined therapy in the 47 patients were as follows: CR, 8 (17.0%); PR, 20 (42.6%); SD, 16 (34.0%) and PD, 3 (6.4%); thus, the ORR was 59.6%. During the observation period, disease progression and death occurred in 19 (40.4%) and 9 (19.1%) patients, respectively, and the median PFS and OS were 18 months and not reached, respectively. Univariate analyses identified the following significant predictors for poor prognostic outcomes: lack of nephrectomy, liver metastasis, bone metastasis, elevated CRP and IMDC poor risk for PFS; and lack of nephrectomy, non-CCC and elevated CRP for OS. AEs and those corresponding to grade ≥ 3 occurred in all (100%) and 30 (63.8%) patients, respectively. CONCLUSIONS: To our knowledge, this is the first study focusing on real-world outcomes following pembrolizumab and axitinib for treatment-naïve advanced Japanese RCC patients, which showed the efficacy and safety of this combined therapy being similar or even superior to those in clinical trial.

The poor antitumor effect of pembrolizumab in advanced upper urothelial carcinoma with renal parenchymal invasion.

OBJECTIVES: We investigated poor prognosticators in advanced or unresectable urothelial carcinoma, focusing on renal parenchymal invasion (RPI). METHODS: This study included 48 bladder cancer (BC) and 67 upper tract urothelial carcinoma (UTUC) patients treated with pembrolizumab from December 2017 to September 2022 at Kobe University Hospital. Medical records were retrospectively reviewed for clinical characteristics, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Multivariate analyses were performed using the Cox proportional hazard regression model to identify parameters associated with either PFS or OS. RESULTS: Of 67 UTUC patients, 23 had RPI and 41 patients did not, while 3 cases could not be evaluated. Patients with RPI were predominantly elderly and had liver metastases. ORR for patients with RPI was 8.7%, while it was 19.5% for those without RPI. PFS was significantly shorter for patients with RPI compared with those without RPI. Patients with RPI had significantly shorter OS than those without RPI. On multivariate analysis, performance status (PS) ≥ 2, neutrophil-lymphocyte ratio (NLR) ≥ 3, C-reactive protein ≥0.3 mg/dL and RPI were independent prognostic factors for PFS. PS ≥ 2, NLR ≥ 3, visceral metastasis and RPI were independent prognostic factors for OS. UTUC patient OS was significantly shorter than BC patient OS, while no significant difference in PFS or OS was observed between BC patients and UTUC patients without RPI. CONCLUSIONS: RPI was a poor prognostic factor in advanced urothelial carcinoma treated with pembrolizumab, possibly resulting in a poorer prognosis for UTUC compared with BC.

Association of sunitinib concentration and clinical outcome in patients with metastatic renal cell carcinoma treated with a 2-week-on and 1-week-off schedule.

WHAT IS KNOWN AND OBJECTIVE: Sunitinib is used as a first-line therapy for metastatic renal cell carcinoma. The primary aim of this study was to determine the optimal total sunitinib (sunitinib plus N-desethyl sunitinib) trough concentration for the alternative dosing schedule: 2-week-on and 1-week-off schedule (2/1 schedule). METHODS: Patients with metastatic renal cell carcinoma treated with the 2/1 schedule of sunitinib, whose total sunitinib concentrations were available, were recruited for this study. Out of 19 patients, 17 whose sunitinib dosage was not changed until the measurement of drug concentration were eligible for the analysis of the relationship between total sunitinib concentration and clinical outcome. Individual pharmacokinetic parameters in 19 patients were estimated via the Bayesian analysis. RESULTS: The onset of severe (grade ≥3) adverse effects among 17 patients during 3 weeks as a first course of sunitinib therapy was observed in 7 (41.2%) patients. The median total sunitinib concentration in patients with severe adverse effects was significantly higher compared with that in patients without severe adverse effects [median: 119 (113-131) vs. 87.8 (77.4-102) ng/mL, p = 0.01]. According to the receiver operating characteristic analysis of the onset of severe adverse effects, the cut-off value of the total sunitinib concentration was 108 ng/mL. Patients with a total sunitinib concentration lower than 108 ng/mL had a longer time to first dose reduction or withdrawal due to adverse effects compared with those with a total sunitinib concentration of 108 ng/mL or higher (p = 0.03). The probability without treatment failure was not significantly different between the two concentration groups. In addition, the estimated sunitinib apparent oral clearance (CL/F) was significantly lower in the severe adverse effects group. Our simulation demonstrated that 0.67-time dose is needed for patients with approximately 90.0 ng/mL of sunitinib concentration on day 7 to maintain the concentration at the same level as the patients with higher CL/F. WHAT IS NEW AND CONCLUSION: Maintaining the total sunitinib trough concentrations of less than 108 ng/mL is safe to avoid the onset of serious adverse effects without increasing the treatment failure in patients with metastatic renal cell carcinoma treated with the 2/1 schedule of sunitinib.

The Efficacy of Surgical Metastasectomy for Solitary Metastasis of Renal Cell Carcinoma.

BACKGROUND: Patients with solitary metastasis of renal cell carcinoma (RCC) have shown to be ideal candidates for surgical metastasectomy (SM). However, whether SM will show more benefit than systemic therapy remains unclear. METHODS: We included 73 patients treated for solitary metastasis after nephrectomy at our institute from April 2008 to December 2018. We compared the clinical outcomes between the SM (n = 29) and no-SM (n = 44) group which were treated with only systemic therapy. RESULTS: Eleven of 29 patients in the SM group received presurgical targeted therapy (PTT). Although 13 of 29 patients in the SM group showed recurrence during the study period, a Cox proportional hazards model showed that SM was significantly associated with a favorable overall survival (hazard ratio: 0.18; p = 0.007). Patients receiving PTT prior to SM showed a longer recurrence-free survival after SM in comparison to those who underwent SM without PTT (median: not reached vs. 27.7 months; p = 0.009). CONCLUSIONS: If resection is feasible, SM may be beneficial for patients with solitary metastasis of RCC, and we showed the possibility that PTT prior to SM may be effective for avoiding recurrence after SM. Further large-scale prospective studies are needed to clarify the ideal treatment strategy for metastatic RCC.

Comprehensive assessments of immuno-oncology drug-based combination therapies as first-line treatment for advanced renal cell carcinoma.

Over the last decade, there have been substantial progress in the field of systemic therapy for advanced renal cell carcinoma. Through the transition from treatment with cytokines to molecular-targeted agents, and currently to immuno-oncology drugs, the prognostic outcomes of patients with advanced renal cell carcinoma have been markedly improved. In particular, based on the promising outcomes of recently conducted pivotal randomized clinical trials, immuno-oncology drug-based combination therapy by either dual immune checkpoint inhibition or combined inhibition of an immune checkpoint and tyrosine kinase, is currently regarded as a standard of care for treatment-naïve advanced renal cell carcinoma patients. However, insufficient data are available with respect to the selection of optimal systemic therapies for advanced renal cell carcinoma in the first-line setting due to the lack of a head-to-head comparison between approved immuno-oncology drug-based combination therapies. In this review, therefore, we summarize interesting findings associated with first-line combination therapies for advanced renal cell carcinoma obtained from both randomized clinical trials and real-world clinical practices, in order to present useful guidance to help make treatment decisions for patients with treatment-naïve advanced renal cell carcinoma.

Robot-assisted partial nephrectomy with minimum follow-up of 5 years: A multi-center prospective study in Japan.

OBJECTIVES: Robot-assisted partial nephrectomy is widely performed for small renal masses, achieving excellent perioperative and intermediate oncological outcomes. However, long-term oncological, functional, and quality of life outcomes after robot-assisted partial nephrectomy remain unclear. In this study, we aimed to evaluate quality of life at 1 year and oncological and functional outcomes of robot-assisted partial nephrectomy after a minimum follow-up of 5 years. METHODS: Personal, perioperative, postoperative, functional, oncological, and quality of life data were evaluated. The EQ-5D-5L tool, which incorporates health profiles and a EuroQol Visual Analog Scale, was used to assess quality of life preoperatively and 365 days postoperatively. Regarding oncological and functional outcomes, overall survival, recurrence-free survival, and changes in estimated glomerular filtration rate were calculated. RESULTS: There were few changes in levels between the two time points for all EQ-5D dimensions. The mean change in EQ-5D-5L was 0.020 (95% confidence interval 0.006-0.033, P = 0.006), and in EuroQol Visual Analog Scale score 4.60 (95% confidence interval 2.17-7.02, P = 0.0003). Overall and recurrence-free survival 5 years after robot-assisted partial nephrectomy were 97.9% and 92.8%, respectively. After an early postoperative decrease, the estimated glomerular filtration rate remained stable over time. CONCLUSIONS: Robot-assisted partial nephrectomy in patients with a T1 renal tumor is safe, feasible, and effective from the perspective of quality of life and survival, even after 5 years. When making treatment decisions, perioperative and quality of life outcomes should be considered together with long-term oncological outcomes.

Development of bioabsorbable zinc-magnesium alloy wire and validation of its application to urinary tract surgeries.

PURPOSE: Metallic medical devices are typically constructed from non-bioabsorbable metals that remains in the body and causes considerable complications. Particularly in the urinary tract, calculus, intractable infection, and misdiagnosis as calculus are often caused by non-bioabsorbable metals. Here, we developed a zinc-magnesium alloy as a new bioabsorbable metal and sought to evaluate the bioabsorbable behavior of zinc and zinc-magnesium alloy in a rat bladder implantation model. METHODS: We prepared zinc-magnesium alloy wires with various proportions of magnesium and investigated the strength, shape retention, formability, and absorbability of these novel materials. Then, we implanted zinc and zinc-magnesium alloy rings formed by the wires into rat bladder. Rats were euthanized at the end of the observation period, and the rings were removed for volume evaluation. Extracted bladder tissues were subjected to histological analysis. RESULTS: The strength of the zinc wire was enhanced by more than fourfold upon the addition of magnesium, without loss of ductility. Linear reduction of ring volume in urine was observed based on the concentration of magnesium within the ring. Nearly all rings were covered with a thin layer of calculus. Histological findings of the transected urinary bladder tissues did not differ among groups. CONCLUSIONS: Zinc-magnesium alloy is a promising candidate for use as a bioabsorbable medical device in the urinary tract.

Treatment outcomes of molecular targeted therapy following nivolumab in metastatic renal cell carcinoma.

OBJECTIVE: The purpose of this study was to assess the therapeutic efficacy of molecular targeted therapies following nivolumab in metastatic renal cell carcinoma and to examine the relationship between therapeutic efficacy and the specific molecular targeted therapy used. METHODS: We retrospectively reviewed the medical records of 115 metastatic renal cell carcinoma patients who were treated with nivolumab at our institution and five affiliated hospitals. Among them, 52 patients who received subsequent molecular targeted therapy following nivolumab were selected to survey treatment outcomes. Progression-free survival and overall survival were estimated with Kaplan-Meier curves, and differences were analyzed by the log-rank test. RESULTS: Among the 52 eligible patients, 40 (76.9%) were treated with tyrosine kinase inhibitors and 12 (23.1%) were treated with mammalian target of rapamycin inhibitor. The median time to treatment failure and progression-free survival of subsequent molecular targeted therapy were 5.6 and 8.0 months, respectively. The median overall survival from the initiation of first-line therapy was not reached. The disease control rate of subsequent molecular targeted therapy was 69.2% (partial response: 25.0%, stable disease: 44.2%). The median progression-free survival of subsequent tyrosine kinase inhibitor and mammalian target of rapamycin inhibitor were 9.2 and 8.0 months, respectively (P = 0.37). The progression-free survival of patients whose best response to prior nivolumab was either progressive disease or stable disease/partial response were 6.3 and 11.3 months, respectively (P = 0.36). CONCLUSIONS: Molecular targeted therapies following nivolumab had comparatively better therapeutic efficacy, which was confirmed regardless of the type of molecular targeted agent used.

Prognostic impact of bone metastatic volume beyond vertebrae and pelvis in patients with metastatic hormone-sensitive prostate cancer.

BACKGROUND: Although bone metastasis beyond the vertebrae and pelvis has been a key factor in prognostic models of metastatic hormone-sensitive prostate cancer (mHSPC), the clinical significance of it is still unclear. The present study evaluated the prognostic impact of the volume of bone metastasis beyond the vertebrae and pelvis on the outcomes of mHSPC and created an ideal risk classification based on it. METHODS: We retrospectively reviewed 197 patients with mHSPC who were treated with combined androgen blockade as the initial treatment between June 2003 and October 2019. We calculated the bone scan index (BSI), including the BSI beyond the vertebrae and pelvis (bBSI), using BONENAVI, and investigated the association between the BSI and the overall survival (OS) of mHSPC. RESULTS: According to the CHAARTED criteria, 91 and 106 patients were classified into the low- and high-volume groups, respectively. Of the 79 patients who did not have visceral metastasis in the high-volume group, those with a bBSI ≤ 0.27 (n = 16) showed a favorable OS, as did those in the low-volume group. The modified CHAARTED high-volume group (presence of visceral metastases or 4 bone lesions with a bBSI > 0.27) showed a significantly shorter OS than others, with a hazard ratio (HR) of 4.69 (p < 0.001), which was higher than that observed with the original CHAARTED criteria (HR = 4.33). CONCLUSIONS: Our data suggested that considering the volume of bone metastasis beyond the vertebrae and pelvis may help to improve the accuracy of risk classification. Further large-scale prospective studies are needed to validate our findings.

Comparison of robot-assisted partial nephrectomy for complex (RENAL scores ≥10) and non-complex renal tumors: A single-center experience.

OBJECTIVES: To compare functional and surgical outcomes of robot-assisted partial nephrectomy for complex tumors with RENAL scores ≥10 and non-complex tumors at a single academic institution. METHODS: We retrospectively analyzed the data of all patients who underwent robot-assisted partial nephrectomy at Kobe University Hospital (Kobe, Hyogo, Japan) from 2011 to 2020. Functional and surgical outcomes for complex tumors (RENAL score ≥10) were compared with those of patients with non-complex tumors (RENAL <10). Outcomes analyzed included blood loss, warm ischemia time, console time, perioperative complications, and preoperative and postoperative renal function. RESULTS: A total of 348 patients were included in our present study, with a median follow-up time of 35.1 months. Of these, 299 patients (85.9%) had non-complex tumors and 49 patients (14.1%) had complex tumors. Warm ischemia time and console time were significantly longer in the complex tumors group. Major perioperative complications (Clavien-Dindo classification system ≥3) were significantly more frequent in the complex tumors group than the non-complex tumor group (16.3% vs 5.7%, P = 0.018). Postoperative preservation of estimated glomerular filtration rate and percentage of chronic kidney disease upstage by 1 year were significantly inferior in the complex tumors group. The positive surgical margin rate was 0% and 0.3% in the complex and non-complex tumor groups, respectively. There were no significant differences in recurrence-free survival between the two groups (P = 0.11). CONCLUSIONS: Robot-assisted partial nephrectomy for complex renal tumors is safe, with no difference in oncological outcomes, although more postoperative complications and decreased renal function can be observed than non-complex tumors.

Diagnostic and therapeutic value of pelvic lymph node dissection in the fossa of Marcille in patients with clinically localized high-risk prostate cancer: Histopathological and molecular analyses.

BACKGROUND: The optimal extent of lymph node dissection in radical prostatectomy has not been determined. Lymph nodes in the fossa of Marcille, which is an important pelvic lymphatic pathway and candidate for additional dissection, have not been evaluated at the molecular level. Here, we assessed by molecular analysis the presence of occult positive lymph nodes in the fossa of Marcille in patients with clinically localized high-risk prostate cancer. METHODS: Fifty-two patients with clinically localized high-risk prostate cancer underwent pelvic lymph node dissection accompanied by robot-assisted radical prostatectomy. All nodal packets were dissected separately and grouped into right and left obturator, external and internal iliac regions (including common iliac region to ureter crossing), and fossa of Marcille. All lymph nodes were bisected and evaluated by histopathological or molecular analysis using a quantitative reverse transcription-polymerase chain reaction. The number of positive lymph nodes in the fossa of Marcille and the difference in detection rate were investigated using histopathological and molecular analyses. Perioperative complication rate and predictive factors for biochemical recurrence were evaluated. RESULTS: In the molecular analysis, there were seven positive lymph nodes in the fossa of Marcille in three patients, which were coexistent with positive nodes in other regions. The detection rate of positive lymph nodes was significantly higher using molecular than histopathological analysis (P < .01). Perioperative complication rate within 90 days after the operation was 25.0% and no Clavien-Dindo grade ≥3 complication was confirmed. Detection of metastasis by histopathological and molecular analysis was a significant factor related to biochemical recurrence in the Cox proportional hazards regression model. CONCLUSIONS: No case of positive lymph nodes in the fossa of Marcille that had skipped over other regions was confirmed. Additional lymph node dissection of fossa of Marcille did not lead to complete resection of molecularly positive lymph nodes.

A comparison of laparoendoscopic single-site surgery versus conventional procedures for laparoscopic donor nephrectomy: a Japanese multi-institutional retrospective study.

PURPOSE: Laparoendoscopic single-site donor nephrectomy (LESSDN) is a feasible and effective procedure because of its non-invasiveness and better cosmetic outcomes. However, there have been few multi-institutional studies conducted by multiple surgeons on LESSDN. We retrospectively compared the clinical data and outcomes between LESSDN and conventional laparoscopic donor nephrectomy (LDN) at multiple institutes in Japan. MATERIALS AND METHODS: From 2009 to 2015, the clinical data of 223 donors who underwent LESSDN and 151 donors who underwent LDN were collected from 10 institutes. All LESSDNs were performed transperitoneally, whereas LDNs were performed transperitoneally (P-LDN) in 75 patients and retroperitoneally (R-LDN) in 76 patients. RESULTS: In the LESSDN group, the single-incision site was pararectal in 155 (69.5%) patients and umbilical in 65 (29.1%) patients. Multiple surgeons (one to eight per institute) performed the LESSDN. No significant differences were observed between the three groups regarding estimated blood loss and warm ischemic time. The operative time was significantly shorter in the LESSDN group than in the R-LDN group (p = 0.018). No significant differences were observed regarding the rates of blood transfusion, open conversion, visceral injuries, and postoperative complications. Furthermore, no significant differences were observed regarding the dose of analgesic and the rate of delayed graft function. One patient required open conversion due to injury to the renal artery. Selection of LESS procedure was not an independent risk factor for the median serum creatinine level of above 1.27 mg/dL in recipients at 1 year after kidney transplantation. CONCLUSION: The results showed the technical feasibility of LESSDN compared with the standard LDNs in a multi-institutional and multi-surgeon setting. A few observed non-negligible complications and the significantly higher levels of serum creatinine in patients who underwent LESSDN indicate that this procedure should be employed cautiously when performed by surgeons without ample experience in performing LESS procedures.

Clinical outcomes of second-line treatment following prior targeted therapy in patients with metastatic renal cell carcinoma: a comparison of axitinib and nivolumab.

BACKGROUND: Sequential treatment starting with target therapy is still the standard care for metastatic renal cell carcinoma (mRCC), even in the era of immune checkpoint inhibitors. Our objective was to compare the clinical outcomes between axitinib and nivolumab as second-line therapy following prior targeted therapy in mRCC patients. METHODS: We identified 41 patients treated with axitinib and 39 patients treated with nivolumab as a second-line regimen after targeted therapy, and retrospectively compared the treatment efficacy and safety in these patients. RESULTS: The clinical benefit rate of axitinib was significantly higher than that of nivolumab (82.9% versus 56.4%; p = 0.014) and patients who received axitinib tended to show longer progression-free survival (PFS) than those who received nivolumab (10.3 months versus 7.3 months; p = 0.067). There was no difference in the overall survival (OS) of the two groups (both not reached; p = 0.581). The incidence of grade ≥ 3 adverse events (AEs) was similar between the two groups, but one patient in the nivolumab group died due to an immune-related AE. In addition, a Cox proportional hazards model showed that the pre-treatment KPS, the baseline neutrophil-to-lymphocyte ratio (NLR), and an objective response in second-line therapy were significantly associated with PFS, while the pre-treatment KPS, the number of metastatic organs, and an objective response in second-line therapy significantly contributed to the predicted OS. CONCLUSIONS: Although the prognosis did not differ markedly between the two groups, axitinib resulted in a better tumor response rate. Further randomized prospective studies are needed for the ideal order of this sequential treatment.

C-reactive protein and the neutrophil-to-lymphocyte ratio are prognostic biomarkers in metastatic renal cell carcinoma patients treated with nivolumab.

BACKGROUND: Association between systemic inflammation and clinical outcome of immune checkpoint inhibitors (ICIs) has received focus. Our objective was to evaluate the utility of the neutrophil-to-lymphocyte ratio (NLR) in metastatic renal cell carcinoma (mRCC) patients treated with nivolumab as well as the prognostic impact of the C-reactive protein (CRP) level. MATERIALS AND METHODS: Sixty-five mRCC patients treated with nivolumab were enrolled. We retrospectively investigated several factors, including the NLR and the CRP level, for their association with progression-free survival (PFS) and overall survival (OS). In addition, we evaluated their impact on the objective response. RESULTS: The CRP level was confirmed to be positively correlated with the NLR in a correlation analysis. An NLR ≥ 5 was significantly associated with a worse PFS (hazard ratio [HR]: 4.54, 95% confidence interval [CI] 1.93-10.7; p < 0.001), and an NLR ≥ 5 and a CRP ≥ 2.1 mg/dL were identified as a significant factors predicting worse OS with HRs of 4.88 (95% CI 1.35-17.7; p < 0.016) and 3.89 (95% CI 1.01-15.0; p = 0.049), respectively. In addition, patients with a ≥ 25% decrease in the NLR and CRP level showed a significantly better response to nivolumab than those without a ≥ 25% decrease in the NLR and CRP level, with odds ratios of 9.54 (95% CI 2.09-49.8, p = 0.001) and 4.36 (95% CI 1.03-18.9, p = 0.032), respectively. CONCLUSION: Both the NLR and CRP levels were significantly associated with the clinical outcome of nivolumab in mRCC patients. The potential prognostic impact of those markers needs to be further prospectively investigated.