Survival Impact of Glucocorticoid Administration for Adverse Events During Immune Checkpoint Inhibitor Combination Therapy in Patients with Previously Untreated Advanced Renal Cell Carcinoma.

BACKGROUND: The impact of glucocorticoid administration for adverse events (AEs), including immune-related AEs, on the effectiveness of immune checkpoint inhibitor (ICI) combination therapy for advanced renal cell carcinoma (RCC) remains unknown. OBJECTIVES: To clarify the prognostic impact of glucocorticoid use for AEs during first-line ICI combination therapy for advanced RCC. PATIENTS AND METHODS: We retrospectively evaluated data from 194 patients who received dual ICI combination therapy [i.e., immunotherapy (IO)-IO] or combinations of ICIs with tyrosine kinase inhibitors (TKIs) as first-line therapy. The patients were divided into two groups according to the history of glucocorticoid administration in each treatment group. Survival based on glucocorticoid administration was assessed. RESULTS: A total of 101 (52.0%) and 93 (48.0%) patients received IO-IO and IO-TKI combination therapy, respectively. Glucocorticoids were administered to 46 (46%) and 22 (24%) patients in the IO-IO and IO-TKI groups, respectively. In the IO-IO group, progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with glucocorticoid administration than in those without administration (median PFS: 14.4 versus 3.45 months, p = 0.0005; median OS: 77.6 versus 33.9 months, p = 0.0025). Multivariable analysis showed that glucocorticoid administration was an independent predictor of longer PFS (hazard ratio: 0.43, p = 0.0005) and OS (hazard ratio: 0.35, p = 0.0067) after adjustment for covariates. In the IO-TKI group, neither PFS nor OS significantly differed between patients treated with and without glucocorticoid administration (PFS: p = 0.0872, OS: p = 0.216). CONCLUSIONS: Glucocorticoid administration did not negatively impact the effectiveness of ICI combination therapy for RCC, prompting glucocorticoid treatment use when AEs develop.

Impact of body composition on outcomes of immune checkpoint inhibitor combination therapy in patients with previously untreated advanced renal cell carcinoma.

BACKGROUND: Data on the association between body composition and outcomes in patients with advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitor (ICI) combination therapy are limited. METHODS: We retrospectively evaluated the clinical and radiographic data of 159 patients with advanced RCC, including 84 receiving ICI dual combination therapy (immunotherapy [IO]-IO group) and 75 receiving combinations of ICIs with tyrosine kinase inhibitors (TKIs) (IO-TKI group). Pretreatment computed tomography images were used to calculate body composition, including skeletal muscle mass and fat tissue area. Sarcopenia was defined based on skeletal muscle and psoas muscle indexes. The total fat index, subcutaneous fat index (SFI), and visceral fat index were also calculated. RESULTS: In the IO-IO treatment group, there was no significant association between body composition and survival or tumor response (P > 0.05). In the IO-TKI treatment group, the high SFI was associated with longer progression-free survival (hazard ratio, 2.70; P = 0.0091) and overall survival (hazard ratio, 26.0; P = 0.0246) than the low SFI, which remained significant after adjusting for covariates. Furthermore, in the high-SFI population, patients treated with IO-TKI therapy had longer progression-free survival (P = 0.0019) and overall survival (P = 0.0287) than those treated with IO-IO therapy, while there was no significant survival difference between the 2 treatment groups in the low-SFI population (P > 0.05). CONCLUSION: The SFI can be potentially utilized as an effective predictive and prognostic biomarker for first-line ICI combination therapy for advanced RCC.

Safety of Docetaxel in a Patient with Metastatic Castration-Resistant Prostate Cancer After Kidney Transplantation: A Case Report.

BACKGROUND: There are limitations in treating advanced prostate cancer (PC), especially castration-resistant (CR) cases, in renal transplant recipients (RTRs). We describe the case of RTR with metastatic CRPC (mCRPC) treated with docetaxel. CASE REPORT: A 60-year-old man with end-stage renal disease due to autosomal-dominant polycystic kidney disease (ADPKD) underwent living-related kidney transplantation. A year later, he was diagnosed with PC (prostate-specific antigen level: 998 ng/mL). Prostate biopsy revealed prostatic adenocarcinoma with a Gleason score of 4 + 4 = 8. Radiographic examination revealed seminal vesicle invasion and multiple bone and lymph node metastases. Combined androgen blockade therapy was initiated; however, the patient was diagnosed with CRPC 6 months later. Triweekly docetaxel therapy was administered 28 months after diagnosis. The patient successfully completed 7 cycles of this therapy without major adverse events. However, after the 7th cycle, he developed a high fever caused by an infection of ADPKD-associated renal cysts. Therefore, docetaxel was discontinued, and enzalutamide was started, followed by abiraterone, but without any effect. We then introduced cabazitaxel but discontinued it because of hepatic dysfunction. Hence, the patient underwent a docetaxel rechallenge. He was administered the PEGylated form of the recombinant human granulocyte colony-stimulating factor for neutropenia prophylaxis. After 6 cycles of rechallenge docetaxel therapy, the patient accidentally fell, resulting in a cervical spine fracture and subsequent death due to respiratory failure. CONCLUSIONS: Docetaxel can be safely delivered to patients with CRPC after renal transplantation who are taking oral immunosuppressants. It can be a good treatment option for them.

Advanced Renal Cell Carcinoma With Inferior Vena Cava Thrombus Treated With a Combination of Preoperative Lenvatinib and Pembrolizumab.

BACKGROUND/AIM: Lenvatinib plus pembrolizumab combination therapy is a safe and effective treatment for patients with advanced renal cell carcinoma (RCC). However, there are no reports of the use of lenvatinib and pembrolizumab combination therapy for RCC with an inferior vena cava (IVC) tumor thrombus. Herein, we describe a case in which pembrolizumab and lenvatinib combination therapy was effectively used to treat RCC with the IVC tumor thrombus extending to the right atrium. CASE REPORT: A 73-year-old man was diagnosed with a right renal tumor with the IVC tumor thrombus extending to the right atrium and multiple pulmonary metastases (cT3cN0M1). Using a computed tomography-guided renal tumor biopsy, the tumor was diagnosed as clear cell RCC. The International Metastatic RCC Database Consortium risk classification was poor according to three risk factors, and lenvatinib and pembrolizumab combination therapy was initiated. The primary renal tumor shrunk, the IVC tumor thrombus that reached the right atrium was reduced from level 4 to level 2, and the lung metastases disappeared 4 months after treatment initiation. Thereafter, a robot-assisted deferred cytoreductive nephrectomy was successfully performed. Pathologically, owing to the preoperative combination therapy, most of the tumor tissue was necrotic; however, some viable cells were present in the primary tumor and IVC tumor thrombus. Eight months following the operation, the patient remains recurrence-free. CONCLUSION: Treatment with lenvatinib and pembrolizumab combination therapy led to tumor shrinkage and allowed robot-assisted nephrectomy in a patient with advanced RCC with the IVC tumor thrombus extending to the right atrium, corroborating the efficacy of the treatment.

Prognostic Value of the Lung Immune Prognostic Index on Recurrence after Radical Surgery for High-Risk Renal Cell Carcinoma.

With emerging options in immediate postoperative settings for high-risk renal cell carcinoma (hrRCC), further risk stratification may be relevant for informed decision making. Balancing the benefits and drawbacks of adjuvant immunotherapy is recommended. We aimed to evaluate the effects of the lung immune prognostic index (LIPI) in this setting. This bi-institutional retrospective study recruited 235 patients who underwent radical surgery for hrRCC between 2004 and 2021. LIPI scores were calculated based on the derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels. The association between LIPI scores and local or distant recurrence was analyzed, along with other possible clinical factors. The median recurrence-free survival (RFS) period was 36.4 months. Based on the LIPI scores, 119, 91, and 25 patients were allocated to the good, intermediate, and poor groups, respectively. The RFS was significantly correlated with the LIPI scores, and the 36 month survival rates were 67.3, 36.2, and 11.0% in the good, intermediate, and poor groups, respectively. In the multivariate model, the LIPI independently predicted the RFS, along with symptoms at diagnosis, Eastern Cooperative Oncology Group performance status, pT status, pN status, and tumor grade. The C-index of the LIPI in predicting RFS was 0.63, and prediction accuracy improved with the addition of the LIPI to both GRade, Age, Nodes, Tumor, and the UCLA Integrated Staging System. Conclusively, the LIPI can be a significant prognostic biomarker for predicting hrRCC recurrence, particularly for identifying the highest-risk cohort.

First-line dual immune checkpoint inhibitor therapies versus combination therapies comprising immune checkpoint inhibitors and tyrosine kinase inhibitors for advanced renal cell carcinoma: a comparative analysis of the effectiveness using real-world data.

BACKGROUND: There are few comparative studies on dual immune checkpoint inhibitors (ICIs) (i.e., IO-IO) and combination therapies comprising ICIs plus tyrosine kinase inhibitors (TKIs) (i.e., IO-TKI) for advanced renal cell carcinoma (RCC), especially in real-world settings. METHODS: We retrospectively evaluated data of 175 patients with IMDC intermediate-risk or poor-risk RCC; as first-line therapy, 103 received IO-IO, and 72 received IO-TKI. An inverse probability of treatment weighting (IPTW) analysis was conducted to balance patients' backgrounds in the IO-IO and IO-TKI groups. RESULTS: Based on the IPTW analysis, progression-free survival (PFS) was longer in the IO-TKI group than in the IO-IO group (median: 15.6 vs. 8.3 months; p = 0.0386). In contrast, overall survival was not different between groups (median: 46.7 vs. 49.0 months; p = 0.465). Although the IPTW-adjusted objective response rate was not significantly different (51.2% vs. 43.9%; p = 0.359), the progressive disease rate as the best overall response was lower in the IO-TKI group than in the IO-IO group (3.3% vs. 27.4%; p < 0.0001). Regarding the safety profile, the treatment interruption rate was higher in the IO-TKI group than in the IO-IO group (70.3% vs. 49.2%; p = 0.005). In contrast, the IO-IO group had a higher corticosteroid administration rate (43.3% vs. 20.3%; p = 0.001). CONCLUSION: IO-TKI therapy exhibited superior effectiveness over IO-IO therapy in terms of PFS improvement and immediate disease progression prevention and was associated with a higher risk of treatment interruption and a lower risk of needing corticosteroids.

Association Between Kidney Function and Outcomes Following Immune Checkpoint Inhibitor-Based Combination Therapy in Patients With Advanced Renal Cell Carcinoma.

BACKGROUND: It remains unclear whether kidney function affects outcomes following immune checkpoint inhibitor (ICI)-based combination therapy for advanced renal cell carcinoma (RCC). METHODS: We retrospectively evaluated data of 167 patients with advanced RCC, including 98 who received ICI dual combination therapy (ie, immunotherapy [IO]-IO) and 69 who received ICI combined with tyrosine kinase inhibitor (TKI) (ie, IO-TKI). In each regimen, treatment profiles were assessed according to the grade of chronic kidney disease (CKD) as defined by the KDIGO 2012 criteria. RESULTS: Of the 98 patients who received IO-IO, 31 (32%), 30 (31%), 15 (15%), and 22 (22%) had CKD G1/2, G3a, G3b, and G4/5, respectively. Of the 69 patients who received IO-TKI, 18 (26%), 25 (36%), and 26 (38%) had G1/2, G3a, and G3b/4/5, respectively. Regarding efficacy, progression-free survival, overall survival, or objective response rate was not different according to the CKD grade in both treatment groups (P > .05). Regarding safety, the rate of adverse events, treatment interruption, or corticosteroid administration was not different according to the CKD grade in the IO-IO group (P > .05), whereas in the IO-TKI group, the incidence of grade ≥ 3 adverse events were significantly higher (P = .0292), and the rates of ICI interruption (P = .0353) and corticosteroid administration (P = .0685) increased, according to the CKD grade. CONCLUSION: There is a differential safety but comparable efficacy profile between the IO-IO and IO-TKI regimens in patients with CKD. Further prospective studies are required to confirm these findings.

Predicting Recurrence After Radical Surgery for High-Risk Renal Cell Carcinoma: Development and Internal Validation of the "TOWARDS" Score.

BACKGROUND: Considering the reported greater benefits of immunotherapy and its unignorable adverse events in adjuvant therapy for high-risk renal cell carcinoma (hrRCC), accurate prediction may optimize drug use. METHODS: The primary objective of this study was to generate a score-based prognostic model of recurrence-free survival in hrRCC. The study retrospectively evaluated 456 patients at two institutions who underwent radical surgery for nonmetastatic pT3-4 and/or N1-2 or pT2 and G4 disease. Clinical variables deemed universally available were selected through backward stepwise analysis and fitted by a multivariable Cox proportional hazards regression model. A point-based score was derived from regression coefficients. Discrimination, calibration, and decision curve analyses were conducted to evaluate predictive performance. Internal validation with bootstrapping was performed to correct for optimism. RESULTS: The mean follow-up period was 55.3 months, and the median follow-up period was 28.0 months. During the follow-up period, the recurrence rate was 48.2% (n = 220) during a median of 75.7 months. Stepwise variable selection retained age, Eastern Cooperative Oncology Group (ECOG) performance status, presence or absence of symptoms, size of the primary tumor, pathologic T stage, pathologic N stage, tumor grade, and histology. Subsequently, the TOWARDS score (range 0-53) was developed from these variables. Internal validation showed an optimism-corrected C-index of 0.723 and a calibration slope of 0.834. The decision curve analysis showed the superiority of this score over the University of California, Los Angeles (UCLA) Integrated Staging System and GRade, Age, Nodes, and Tumor score. CONCLUSIONS: The authors' novel TOWARDS scoring model had good accuracy for predicting disease recurrence in patients with hrRCC, and the clinical practicability was superior to that of the existing models.

Comparisons of survival and surgical outcomes between minimally invasive partial nephrectomy and radical nephrectomy in elderly patients with stage 1 renal cell carcinoma.

AIM: We compared survival and perioperative outcomes of robot-assisted laparoscopic partial nephrectomy (RAPN) and laparoscopic radical nephrectomy (LRN) for older patients (age 70 years or older) with stage 1 renal cell carcinoma (RCC). METHODS: This retrospective, single-center study included 260 patients who underwent RAPN and 44 patients who underwent LRN. The overall survival (OS) and perioperative outcomes were compared between these two groups using an inverse probability of treatment weighting (IPTW) analysis. RESULTS: Compared with the LRN group, a trend of more complications was observed in the RAPN group, including a higher body mass index (24 vs. 22 kg/m2 ; P = 0.0002) and higher rates of hypertension (77% vs. 55%; P = 0.0029) and chronic kidney disease (62% vs. 36%; P = 0.0027). After adjustment by the IPTW analysis, the RAPN group had a shorter operative time (143 vs. 282 min; P = 0.033), shorter postoperative length of hospital stay (PLOS) (4.1 vs. 7.9 days; P = 0.004), and less change in the estimated glomerular filtration rate during surgery (-8.4% vs. -32%; P < 0.0001) than the LRN group; however, the perioperative complication rates were similar. Patients who underwent RAPN had better 5-year OS than those who underwent LRN (95% vs. 90%; log-rank, P = 0.017). CONCLUSION: RAPN resulted in better OS and surgical outcomes, with shorter operative time, shorter PLOS, and better renal function preservation, than LRN for older patients with stage 1 RCC. Therefore, RAPN may be the primary option for patients indicated for surgical intervention. Geriatr Gerontol Int 2024; 24: 269-274.

Real-world outcomes of nivolumab plus ipilimumab combination therapy for advanced renal cell carcinoma in Japanese patients: data with a minimum of 3 years of follow-up.

BACKGROUND: Long-term follow-up data regarding treatment outcomes of nivolumab plus ipilimumab combination therapy for advanced renal cell carcinoma as a first-line therapy are limited in real-world Japanese populations. METHODS: We retrospectively evaluated data of 56 advanced renal cell carcinoma patients treated with nivolumab plus ipilimumab, with a follow-up of at least 3 years. Survival, tumour response and adverse event profiles were assessed. RESULTS: A total of 41 patients (73%) were histopathologically diagnosed with clear-cell renal cell carcinoma, and 34 (61%) were categorized into the International Metastatic renal cell carcinoma Database Consortium intermediate-risk group. The median follow-up period was 34.4 months. Regarding an effectiveness profile, median progression-free survival, time to treatment failure and overall survival were 9.01, 12.5 and 49.0 months, respectively. Objective response was observed in 27 patients (48%), including eight patients with complete response (14%), and the median duration of response was 30.8 months. Multivariate analyses showed that clear-cell histology was an independent factor of longer overall survival (hazard ratio: 0.23, P = 0.0013). Regarding safety profiles, adverse events of any grade and those with grade ≥3 developed in 40 (71%) and 25 patients (45%), respectively. Median time to adverse event development was 1.68 months. Treatment was interrupted in 28 patients (50%), and corticosteroid administration was needed in 25 (45%). CONCLUSION: The 3-year follow-up data showed that nivolumab plus ipilimumab combination therapy exhibited a feasible effectiveness in real-world Japanese patients with advanced renal cell carcinoma. Accordingly, the high risk of adverse event development, which often requires treatment withdrawal and corticosteroid administration, should be considered.

Renal cell carcinoma outcomes in end-stage renal disease: A 40-year study from two Japanese institutions.

OBJECTIVES: The objective of the study was to analyze the outcomes of patients with renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) over a 40-year span. METHODS: We retrospectively evaluated data of patients with ESRD-RCC diagnosed between 1979 and 2020 at two institutions. We assessed changes in stage, surgical approaches, and cancer-specific survival (CSS) following nephrectomy according to era between ESRD-RCC and sporadic RCC. Furthermore, perioperative outcomes in patients with ESRD-RCC were compared between laparoscopic and open surgery. RESULTS: Patients with ESRD-RCC (n = 549) were diagnosed at an earlier stage (p = 0.0276), and the ratio of laparoscopic nephrectomy was increased (p < 0.0001) according to eras. Since 2000 (i.e., after implementation of laparoscopic nephrectomy), patients with ESRD-RCC (n = 305) had significantly shorter CSS (p = 0.0063) after nephrectomy than sporadic RCC (n = 2732). After adjustment by multivariate analysis and propensity score matching, ESRD status was independently associated with shorter CSS (p = 0.0055 and p = 0.0473, respectively). Improved CSS in sporadic RCC (p < 0.0001), but not ESRD-RCC (p = 0.904), according to era contributed to this difference. Laparoscopic nephrectomy showed favorable outcomes, including shorter surgery time, lower estimated bleeding volumes, transfusion rates, and readmission rates, and shorter postoperative hospitalization than open nephrectomy (p < 0.05). CONCLUSIONS: Advances in diagnostic and treatment modalities potentially enable early diagnosis and minimally invasive surgery for patients with ESRD-RCC. As ESRD-RCC may not present indolently, careful post-operative monitoring is needed.

Predictive factors and oncological outcomes of pathological T3a upstaging in patients with clinical T1 renal cell carcinoma undergoing partial nephrectomy.

OBJECTIVES: To investigate predictive factors and oncological outcomes of pathological T3a upstaging in renal cell carcinoma patients who were initially diagnosed as clinical T1 and treated with partial nephrectomy. METHODS AND MATERIALS: The clinical records and survival data of 1617 patients, who had undergone partial nephrectomy for clinical T1 renal cell carcinoma at Tokyo Women's Medical University, Tokyo, Japan between January 2011 and December 2020, were analyzed retrospectively. RESULTS: Of 1617 clinical T1 renal cell carcinoma patients who underwent partial nephrectomy, 28 (1.73%) had pathological T3a upstaging. In the multivariable analysis for pathological T3a upstaging using logistic regression models, male sex and clinical T1b were significant factors associated with pathological T3a upstaging (male sex: odds ratio = 5.07, 95% confidence interval: 1.18-21.8, clinical T1b: odds ratio = 8.36, 95% confidence interval: 3.56-19.6). The Kaplan-Meier method of the recurrence-free survival showed shorter recurrence-free survival in patients with pathological T3a upstaging than in those with pathological T1 (P < 0.0001). In the multivariable analysis using Cox proportional hazards regression models, pathological T3a upstaging was no longer significantly associated with recurrence-free survival after adjustment for other pathological factors (hazard ratio = 1.59, 95% confidence interval: 0.58-4.36). In a sensitivity analysis that analyzed its components individually instead of whole pathological T3a, neither perinephric fat invasion, sinus fat invasion, nor renal vein invasion was associated with recurrence-free survival. CONCLUSIONS: Male sex and clinical T1b were significant predictors for pathological T3a upstaging after partial nephrectomy in clinical T1 renal cell carcinoma patients. Although patients with pathological T3a upstaging had worse recurrence-free survival compared with those without upstaging, multivariable analyses revealed that pathological T3a upstaging was not an independent predictor for poor recurrence-free survival.

Surgical and functional outcomes of repeat robot-assisted laparoscopic partial nephrectomy compared with repeat open partial nephrectomy.

OBJECTIVES: To examine the surgical and functional outcomes of patients who have undergone repeat open partial nephrectomy (reOPN) or robot-assisted laparoscopic partial nephrectomy (reRAPN). METHODS: Until May 2022, 3310 patients with renal tumors underwent nephron-sparing surgery (NSS) at affiliated institutions. Of these, 22 and 17 patients who underwent reOPN and reRAPN, respectively, were included in this study. RESULTS: No significant differences were found between the groups in terms of sex, age, comorbidities, recurrent tumor size at repeat NSS, interval from recurrence to initial NSS, and nephrometry score. ReRAPN had a shorter operative time (median: 138.0 vs. 214.0 min; p = 0.0023) and less estimated blood loss (median: 50.0 vs. 255.0 mL; p = 0.0261) than reOPN. The incidence of complications with Clavien-Dindo grade ≥ 2 was higher in the reOPN group than in the reRAPN group (31.8 vs. 5.9%; p = 0.0467). The mean decrease in the estimated glomerular filtration rate at 3 months postoperatively was not significantly different between the groups. The trifecta achievement rates in the reRAPN (64.7%) and reOPN (27.3%) groups were significantly different (p = 0.0194). On multivariate analysis, age and surgical method were significant predictors of trifecta achievement after partial nephrectomy. CONCLUSIONS: There were no differences in postoperative renal functional outcomes between reOPN and reRAPN. ReRAPN is superior to reOPN in terms of surgical burden. Therefore, ReRAPN is an important minimally invasive surgery for recurrent renal cell carcinoma.

Clinical Course of Candidate Renal Transplant Recipients Diagnosed With Prostate Cancer During Pre-transplant Screening Test.

BACKGROUND/AIM: Occasionally, candidate renal transplant recipients (RTRs) are incidentally diagnosed with prostate cancer (PCa) during pre-transplant screening examinations; however, their clinical course remains unclear. This study aimed to clarify the clinical course of RTR diagnosed with PCa during pre-transplant screening tests. PATIENTS AND METHODS: Between April 2008 and April 2022, 15 candidates for RTRs were newly diagnosed with PCa during the screening test. We analyzed the patients' treatment choices, initial treatment results, waiting duration for renal transplantation, and whether they finally underwent transplantation. RESULTS: The median patient age was 64 years (range=52-75 years). The median prostate-specific antigen level was 6.9 ng/ml (5.2-56.9 ng/ml). According to D'Amico risk stratification, one, 10, and four patients were at low, intermediate, and high risk, respectively. As for treatment choice, 13 patients chose surgery. Moreover, intensity-modulated radiotherapy and hormone therapy were chosen by one patient each. Of these, seven patients underwent transplantation, with a median waiting time from initial treatment to transplantation of 20.3 months (9.2-40.0 months). One patient discontinued transplantation owing to poor cancer control, four patients had donor issues (change in mind, aging, or disease), and one patient waited because pathological findings revealed locally invasive cancer. CONCLUSION: PCa diagnosis in candidate RTRs during the pre-transplant screening test impacts the candidate's clinical course.

A retrospective cohort study of the impact of peripheral blood gamma- delta T cells to prognosis of nonmetastatic renal cell cancer after curative resection.

AIM: Gamma-delta-T cells (γδT) have potential antitumor roles and have recently been applied in adoptive immunotherapy. In the present study, we focused on the proportion of γδT cells in the peripheral blood just before surgery for renal cell cancer (RCC) and investigated whether their proportion affected recurrence-free survival (RFS) and overall survival (OS) retrospectively. PATIENTS AND METHODS: A total of 137 patients with localized, non-metastatic RCC who received surgery at our institutes were analyzed retrospectively. The patients were divided into 2 groups: normal and low γδT cell groups based on the proportion of peripheral blood γδT cells. Kaplan-Meier curves were constructed to access the association of the proportion of peripheral blood γδT cells to RFS and OS. Cox regression were also constructed to access the risks to prognosis. Uni- and multivariate logistic regressions were performed to access associations between risk factors and, RFS and OS. RESULTS: Among 137 patients, 40 had a proportion of γδT cells in peripheral blood of less than 1%, which was below the normal range. The remaining 97 patients had these cells in peripheral blood at 1% or higher. In the groups with low γδT cells, 13 patients had recurrences, and 9 patients dies during the observation period. In the groups with normal γδT cells, 16 patients had recurrences, and 8 patients died. The normal γδT cell group demonstrated significantly better prognosis in terms of RFS and OS. Multivariate analysis revealed that a low hemoglobin level, a low proportion of γδT cells, and a high pathological T stage (pT) were statistically independent risk factors for RFS. Age, albumin, C-reactive protein (CRP), % γδT cells, and pT were statistically significant factors affecting OS and only pT was an independent risk factor by multivariate analysis. CONCLUSION: A low proportion of γδT cells was identified as one of the risk factors for RFS. Our findings will provide clues to develop strategies for early intervention in preventing recurrence even after complete resection of RCC and, such as adoptive immunotherapy using autologous γδT cells in patients with a low proportion of γδT cells.

Real-world efficacy and safety of cabozantinib following immune checkpoint inhibitor failure in Japanese patients with advanced renal cell carcinoma.

BACKGROUND: Real-world data of cabozantinib after failure of immune checkpoint inhibitors for advanced renal cell carcinoma in Japanese population are limited. Additionally, prognostic factors of cabozantinib in this setting are still unknown. METHODS: We retrospectively evaluated data of 56 patients treated with cabozantinib subsequent to failed immune checkpoint inhibitors at four institutions. Regarding the efficacy profile, progression-free survival, overall survival and objective response rate were assessed. In terms of the safety profile, rate of adverse events, dose reduction and treatment interruption were assessed. Furthermore, risk factors of progression-free survival were analyzed. RESULTS: Twenty-nine patients (52%) were treated with cabozantinib as second-line therapy. Most frequent prior immune checkpoint inhibitor treatment was nivolumab plus ipilimumab combination therapy as first-line therapy (n = 30, 54%). Median progression-free survival and overall survival were 9.76 and 25.5 months, respectively, and objective response rate was 34%. All patients experienced at least one adverse event, and grade ≥ 3 adverse events were observed in 31 patients (55%). Forty-four (79%) and 31 (55%) patients needed dose reduction and treatment interruption, respectively. Multivariate analysis showed that reduced initial dose (i.e. <60 mg) (hazard ratio: 2.50, P = 0.0355) and presence of lymph node metastasis (hazard ratio: 2.50, P = 0.0172) were independent factors of shorter progression-free survival. CONCLUSION: Cabozantinib in Japanese patients with advanced renal cell carcinoma who failed immune checkpoint inhibitors was efficacious and had a manageable safety profile. These results appear to be similar to those of previous clinical trials.

A single-center retrospective comparative analysis of urinary continence in robotic prostatectomy with a combination of umbilical ligament preservation and Hood technique.

OBJECTIVES: Data available on the effect of the recently developed Hood technique and its modified iterations in robot-assisted radical prostatectomy on postoperative urinary continence are insufficient. We evaluated the time to achieve urinary continence with the modified Hood technique compared with the standard or umbilical ligament preservation robot-assisted radical prostatectomy. METHODS: This retrospective analysis examines patient records for those who underwent robot-assisted radical prostatectomy at the Jyoban Hospital of Tokiwa Foundation in Fukushima, Japan, from 2017 to 2021. The main outcome was to determine significant differences in the time taken to achieve urinary continence among the three procedure types. We employed the Kaplan-Meier survival analysis to estimate the time to achieve urinary continence in the three procedure types of robot-assisted radical prostatectomy. Additionally, we used a Cox regression hazard model to evaluate the association between the time to achieve urinary continence and the procedure types. RESULTS: We considered 196 patients in this study. The estimated rates of achieving urinary continence at 6 months following standard, umbilical ligament preservation, and modified Hood technique robot-assisted radical prostatectomy were 77.6%, 89.5%, and 100%, respectively. The multivariable Cox hazard regression model showed that patients who underwent the modified Hood technique were significantly more likely to achieve urinary continence than those who underwent the standard robot-assisted radical prostatectomy. CONCLUSIONS: The modified Hood technique achieved better urinary continence outcomes, with all patients with the procedure achieving urinary continence at 6 months. Further randomized controlled trials are required to validate this finding.

Relationship between changes in quality of life and genitourinary toxicity grade after brachytherapy with I-125 alone for localised prostate cancer.

Background: The relationship between the grading of toxicities based on toxicity criteria and longitudinal changes in quality of life (QOL) scores after permanent prostate brachytherapy (PPB) for localized prostate cancer remains unclear. This study aimed to evaluate these relationships. Materials and methods: We assessed 107 patients treated with PPB using Iodine-125 alone from May 2007 to April 2010. Disease-specific QOL scores before PPB and at 1, 3, 6, 12, and 24 months after PPB were retrospectively evaluated with the Expanded Prostate Cancer Index Composite (EPIC), focusing on urinary domains. Toxicities were graded using the Radiation therapy oncology group and the European organization for research and treatment of cancer toxicity criteria. Results: The median follow-up duration was 116 (range 18-148) months. Thirty-four patients (31.8%) developed grade ≥ 2 acute genitourinary (GU) toxicities; six (5.6%) developed grade ≥ 2 late GU toxicities. The general urinary domain score dropped significantly at 1 month (77.1 ± 14.1) post-PPB compared to the baseline score (92.2 ± 8.2), and then gradually returned to the baseline level by 12 months (93.7 ± 8.3) post-PPB. Reductions in the general urinary domain scores, including its subscale scores at 1, 3, and 6-months post-PPB were significantly greater among patients with grade ≥ 2 GU toxicity than among those with grade 0-1 GU toxicity. Changes in urinary domain scores demonstrated a close relationship with acute GU toxicity grades after PPB. Conclusions: Longitudinal assessments of the EPIC QOL scores provided additional information regarding time-course changes in GU toxicities after PPB.

Association between lung immune prognostic index and survival of patients with metastatic urothelial carcinoma treated with pembrolizumab.

INTRODUCTION AND OBJECTIVE: Lung immune prognostic index score (LIPI), calculated using the derived neutrophil-lymphocyte ratio and lactate dehydrogenase level, is reported for use in numerous malignancies, while its role on metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains limited. We aimed to investigate association between LIPI and outcomes in this setting. METHODS: We retrospectively evaluated 90 patients with mUC treated with pembrolizumab at four institutions. The associations between three LIPI groups and progression-free survival (PFS), overall survival (OS), objective response rates (ORRs) or disease control rates (DCRs) were assessed. RESULTS: Based on the LIPI, good, intermediate, and poor groups were observed in 41 (45.6%), 33 (36.7%), and 16 (17.8%) patients, respectively. The PFS and OS were significantly correlated with the LIPI (median PFS: 21.2 vs. 7.0 vs. 4.0 months, p = 0.001; OS: 44.3 vs. 15.0 vs. 4.2 months, p < 0.001 in the LIPI good vs. intermediate vs. poor groups). Multivariable analysis further revealed that LIPI good (vs. intermediate or poor, hazard ratio: 0.44, p = 0.004) and performance status = 0 (p = 0.015) were independent predictors of a longer PFS. In addition, LIPI good (hazard ratio: 0.29, p < 0.001) were shown to be associated with a longer OS together with performance status = 0 (p < 0.001). The ORRs tended to be different among patients with Good LIPI compared with Poor, and DCRs were significantly different among the three groups. CONCLUSIONS: LIPI, a simple and convenient score, could be a significant prognostic biomarker of OS, PFS, and DCRs for mUC treated with pembrolizumab.

Long-time Survival of a Renal Transplant Recipient With Metastatic Mucinous Tubular and Spindle Cell Carcinoma: A Case Report.

BACKGROUND/AIM: Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare histological type of renal cell carcinoma (RCC). There are few reports of MTSCC occurring in renal transplant recipients (RTRs). The aim of this study was to report a case of long-term survival of a RTR with metastatic MTSCC of the kidney with sarcomatoid changes. CASE REPORT: A 53-year-old male with a left retroperitoneal tumor was referred to our department. He had been receiving hemodialysis since 1991 and underwent kidney transplantation in 2015. Computed tomography (CT) revealed suspected RCC, and a radical nephrectomy was performed in June 2020. Pathological findings revealed MTSCC with sarcomatoid changes. After the surgery, multiple metastases appeared in the bilateral adrenals, skin, para-aortic lymph nodes, muscles, mesocolon, and liver. We treated the patient with metastasectomy, radiation therapy, and sequential systemic therapy with tyrosine kinase inhibitors (TKI). Two years after the initial surgery, the patient died of cancer while controlling its progression. CONCLUSION: We report a RTR with aggressive and metastatic MTSCC with sarcomatoid changes, resulting in a longer survival time relative to multimodal therapy.