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.

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.

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.

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.

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.

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.

Summary of the Clinical Practice Guidelines for Upper Tract Urothelial Carcinoma 2023 by the Japanese Urological Association.

This article is an English translation of the Clinical Practice Guidelines for Upper Tract Urothelial Carcinoma (2nd edition) published in June 2023. The Japanese Urological Association's (JUA) Guidelines Committee on Upper Tract Urothelial Carcinoma (UTUC) created a 2023 update guideline to support clinicians' current evidence-based management of UTUC and to incorporate its recommendations into clinical practice. The new guideline adhered as closely as possible to the Minds Manual for Guideline Development 2020 ver. 3.0. Findings related to epidemiological, pathological, diagnosis, treatment, and follow-up were reviewed. In addition, seven clinical questions (CQs) were set to determine the grade of recommendation and level of evidence. Preconceptions and biases were removed from the preparation process, the overall evidence was evaluated appropriately, and recommendations were made after fully considering the balance between benefits and harms. Although the evidence is still insufficient to be taken up as a CQ, the latest important information is described in seven columns, and clinical issues that should be resolved in the future related to the CQ are described as recommendations for tomorrow. We hope that these guidelines will help medical professionals, patients, and their families involved in the treatment of UTUC in their decision-making, and hope that a critical review of these guidelines will lead to further refinements in the next edition.

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.

Impact of sex on prognosis in patients with advanced renal cell carcinoma treated with immune checkpoint inhibitors.

BACKGROUND: Prognostic impact of sex in patients with malignancies treated with immune checkpoint inhibitors has been intensively discussed but remains unclear, especially in advanced renal cell carcinoma. METHODS: We retrospectively evaluated a total of 184 patients with advanced renal cell carcinoma treated with either nivolumab plus ipilimumab combined treatment as first-line therapy (n = 73) or nivolumab as later-line therapy (n = 111) at our affiliated institutions. Progression-free survival, overall survival and objective response rate as well as adverse event profile were compared between sexes. RESULTS: Of the total 184 patients, 48 (26%) were female. Female patients had a significantly shorter progression-free survival than male patients (median: 3.8 vs. 8.3 months, P = 0.0005), but overall survival (median: 39.2 vs. 45.1 months, P = 0.283) and objective response rate (29% vs. 42%, P = 0.119) were not different between them. Similar findings were observed when analyzing within each treatment; in both patient groups treated with nivolumab plus ipilimumab combined therapy and nivolumab monotherapy, progression-free survival was significantly shorter in female than in male patients (P = 0.007, P = 0.017), but overall survival (P = 0.914, P = 0.117) and objective response rate (P = 0.109, P = 0.465) were comparable between them. Moreover, in a more restricted cohort consisting of patients with clear-cell renal cell carcinoma, a shorter progression-free survival in female patients was also observed (3.8 vs. 11.0 months, P < 0.0001). CONCLUSIONS: This retrospective study showed that immune checkpoint inhibitors-based treatment for renal cell carcinoma exhibited less marked effects in female than in male patients. Thus, sex may be an important factor for decision-making on systemic therapy as renal cell carcinoma treatment, although further studies are required to validate the present findings.

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.

Comparison of surgical outcomes after robot-assisted laparoscopic partial nephrectomy between patients continuing and discontinuing aspirin therapy: a Japanese single-centre study.

PURPOSE: To investigate the feasibility of continuing aspirin therapy in patients with renal tumours undergoing robot-assisted laparoscopic partial nephrectomy. METHODS: This retrospective, single-centre study included 106 patients receiving aspirin therapy who underwent robot-assisted laparoscopic partial nephrectomy. The patients were divided into two groups, including those continuing and discontinuing aspirin therapy, and their surgical outcomes were compared. To minimise potential bias, variables including patient and tumour characteristics were adjusted using 1:1 propensity score matching. RESULTS: Aspirin therapy was used for ischaemic heart disease in 38 patients (36%), cerebrovascular disease in 21 (20%) and others in 47 (44%). Of the 106 patients, 49 were classified to the continuing group and 57 to the discontinuing group. After matching, 24 patients were included in each group. The surgical outcomes, such as changes in the estimated glomerular filtration rate, estimated blood loss, and surgical margin positivity rate, were not significantly different between the groups. In addition, no significant difference was observed in haemoglobin level changes during surgery (continuing: -2.3 g/dl; discontinuing: -1.7 g/dl, P = 0.0676) and haemorrhagic complications (continuing: 8%; discontinuing: 4%, P = 0.500). Multivariate analysis of predictors for haemoglobin level decrease >2 g/dl or haemorrhagic complications showed that, whereas tumour complexity was an independent predictor, continuation or discontinuation of aspirin therapy was not. CONCLUSION: The surgical outcomes of robot-assisted laparoscopic partial nephrectomy between patients continuing and discontinuing aspirin therapy were not significantly different, thus suggesting the feasibility of continuing aspirin therapy in selected Japanese patients.

Outcomes of nivolumab monotherapy for previously treated metastatic renal cell carcinoma: a real-world multi-institution data with a minimum of 2 years of follow-up.

OBJECTIVES: To investigate the long-term follow-up outcomes of nivolumab monotherapy for previously treated metastatic renal cell carcinoma, using real-world data. METHODS: A total of 121 patients were treated with nivolumab monotherapy as subsequent therapy after the failure of prior tyrosine kinase inhibitor therapy between January 2013 and December 2021 at four affiliated institutions. To evaluate the outcome after 2 years or more, we selected patients in whom nivolumab therapy was started in December 2019 or earlier because data collection was performed until the end of December 2021. RESULTS: Seventy-four patients were evaluated. During the median follow-up period of 25.8 months, 62 (84%) and 40 (54%) patients had disease progression and died, respectively. Nivolumab was administered as second-line therapy in 43 patients (58%). The median progression-free survival and overall survival were 5.52 and 31.1 months, respectively, and objective response rate was 36%. There was no difference in progression-free survival or overall survival based on the treatment line of nivolumab (P = 0.915, P = 0.559). The magnitude of tumor response and development of immune-related adverse events were significantly associated with progression-free survival (P < 0.0001, P < 0.0001, respectively) and overall survival (P < 0.0001, P = 0.0002, respectively). Treatment-related adverse events developed in 38 patients (51%), including 33 (45%) who had immune-related adverse events. Steroid administration was needed in nine patients (12%). CONCLUSIONS: The present real-world multi-institution study with long-term follow-up data demonstrates that nivolumab monotherapy is effective for previously treated metastatic renal cell carcinoma, prolonging survival, improving tumor response and has a manageable safety profile.

Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

OBJECTIVES: To explore the therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. PATIENTS AND METHODS: Forty-one patients with synchronous metastatic renal cell carcinoma who received nivolumab plus ipilimumab as first-line systemic therapy at our affiliated institutions were retrospectively evaluated. We focused on the prognosis, including tumor responses in primary kidney and metastatic lesions in patients treated with deferred cytoreductive nephrectomy. In addition, the overall survival according to nephrectomy status (i.e. deferred cytoreductive nephrectomy vs. upfront cytoreductive nephrectomy vs. without cytoreductive nephrectomy) was compared. RESULTS: During a median follow-up period of 12.0 months, seven (30%) patients received deferred cytoreductive nephrectomy at a median time of 10.4 months after nivolumab plus ipilimumab initiation. All the patients showed tumor shrinkage in their primary kidney lesions, including six (86%) patients with ≥30% of shrinkage. Metastatic lesions were also shrunk by ≥30% in six (86%) patients, including two (29%) obtaining complete response. At the last time of follow-up, three (43%) patients were disease-free. The overall survival rate after nivolumab plus ipilimumab initiation tended to be higher in patients with deferred cytoreductive nephrectomy compared with those with upfront cytoreductive nephrectomy (1-year survival rate: 100% vs. 72.4%, P = 0.0587) and those without cytoreductive nephrectomy (vs. 58.2%, P = 0.0613). CONCLUSIONS: The present retrospective data showed that deferred cytoreductive nephrectomy had the potential to exert a therapeutic effect in a subset of patients who obtained favorable tumor responses to nivolumab plus ipilimumab for a certain period. Prospective randomized clinical trials are needed to confirm the prognostic impact of deferred cytoreductive nephrectomy after frontline immunotherapy in synchronous metastatic renal cell carcinoma.

Risk factors for recurrence after operation in patients with pT1a renal cell carcinoma: sub-analysis of the multi-institutional national database of the Japanese Urological Association.

BACKGROUND: More patients with renal cell carcinoma are now diagnosed with the disease in its early stages. Although patients with pT1a renal cell carcinoma have a good prognosis and low recurrence rate, a few patients still experience recurrence. Herein, we evaluated the clinicopathological risk factors for postoperative recurrence of pT1aN0M0 renal cell carcinoma. METHODS: An renal cell carcinoma survey was conducted by the Japanese Urological Association to register newly diagnosed cases of renal cell carcinoma. A total of 1418 patients diagnosed with pT1aN0M0 renal cell carcinoma who underwent surgery as the primary surgical treatment were included. We analyzed the recurrence-free survival using the Kaplan-Meier method and clinicopathological factors for recurrence using Cox proportional hazards models. RESULTS: Among 1418 patients, 58 (4.1%) had recurrences after a median follow-up of 62.8 months. The median time to recurrence was 31.0 months. Metastases to the lungs and the bone were observed in 20 and 10 cases, respectively. Significant differences in sex, tumor size, Eastern Cooperative Oncology Group performance status, and dialysis history, preoperative hemoglobin levels, C-reactive protein levels and creatinine levels were observed between the recurrence and non-recurrence groups. Multivariate analysis identified male sex, high C-reactive protein level and tumor size ≥3 cm as independent risk factors. The 5-year recurrence-free survival of patients with 0, 1, 2 and 3 risk factors was 99.0, 97.2, 93.1 and 80.7%, respectively. CONCLUSIONS: Male sex, tumor diameter and a high C-reactive protein level were independent recurrence risk factors for pT1a renal cell carcinoma; special attention should be paid to patients with these risk factors during postoperative follow-up.

C-reactive protein kinetics to predict recurrence of high-risk renal cell carcinoma after radical surgery.

BACKGROUND: With new options in adjuvant settings, clinical biomarkers to predict recurrence after radical surgery for high-risk renal cell carcinoma (hrRCC) are in need but are scarcely investigated. We aimed to verify the predictive value of perioperative C-reactive protein (CRP) kinetics on hrRCC recurrence. METHODS: We retrospectively evaluated 154 patients who underwent radical surgery for hrRCC (≥ pT3 and/or N1-2 and M0) at two institutions. Patients were classified into Normal (< 0.5) and High (≥ 0.5) according to their preoperative serum CRP (mg/dL). The High group were further classified into Normalized (< 0.5 at post) or Non-normalized (≥ 0.5 at post), and recurrence-free survival (RFS) was compared between groups. Factors for RFS were further analysed, and Harrell's concordance index (C-index) for the accuracy of predicting RFS was compared with and without the addition of CRP-related variables to pre-existing models. RESULTS: The RFS was significantly shorter in the High (n = 72, 46.8%) compared to the Normal (n = 82, 53.2%) group (9.7 vs. 66.7 months, p < 0.001). Within the High group, Non-normalized (n = 27, 17.5%) patients showed a significantly shorter RFS compared to the Normalized (n = 45, 29.2%) group (6.2 vs. 20.3, p = 0.009). In the multivariable stepwise analysis, CRP kinetics (hazard ratio 2.15, p = 0.029) effectively predicted RFS while baseline CRP fell short of significance. Higher C-index improvement was observed with CRP non-normalization than the baseline value when added to factors in the Karakiewicz and University of California Los Angeles Integrated Staging System models. CONCLUSIONS: CRP kinetics effectively predicted RCC recurrence after surgery and may aid in decision-making for adjuvant systemic therapy.

Surgical and functional outcomes of robot-assisted laparoscopic partial nephrectomy for renal cell carcinoma in adolescents and young adults: a propensity score matching study.

BACKGROUND: Cancer development in adolescents and young adults (AYAs) has elicited recent interest. We investigated the surgical and functional outcomes of robot-assisted laparoscopic partial nephrectomy (RAPN) for renal cell carcinoma (RCC) in AYAs. METHODS: We retrospectively reviewed the medical records of 1023 patients with clinical stage I RCC who underwent RAPN before January 2021. Patients were divided into two groups: AYAs (aged 18-39 years) and non-AYAs (aged 40-89 years). The trifecta criteria, defined as a negative surgical margin, no perioperative complications (Clavien-Dindo grade > 2), and preserved postoperative renal function (1-year postoperative estimated glomerular filtration rate > 90% of baseline), were used to compare outcomes. We performed 1:1 propensity-score matching on the patient cohort. RESULTS: There were initially 125 and 898 patients in the AYAs and non-AYAs groups, respectively, and 108 patients were included in each group after propensity score matching. There were no significant differences in surgical factors (operation time, clamping ischemia time, estimated blood loss, length of hospital stay, surgical complication rate) or renal function in the early postoperative period. The mean postoperative renal function was better (p = 0.0200) and the decrease in estimated glomerular filtration rate was lower (p = 0.0026) in AYAs than in non-AYAs 12 months postoperatively. The trifecta achievement rates in the AYAs and non-AYAs groups were significantly different (67.6% and 53.7%, respectively, p = 0.0220). CONCLUSION: Although there was no difference in surgical burden between the groups, the estimated glomerular filtration rate was better preserved in AYAs than in non-AYAs at 6 and 12 months post-RAPN.

Prognostic Impact of Trial-Eligibility Criteria in Patients with Metastatic Renal Cell Carcinoma.

OBJECTIVE: The aim of the study was to evaluate the prognostic impact of trial-eligibility criteria on outcome in real-world metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs). PATIENTS AND METHODS: mRCC patients treated with TKIs as first-line systemic therapy were retrospectively evaluated. The patients were determined as trial-ineligible when they met at least 1 following trial-ineligible criteria; Karnofsky performance status score <70, hemoglobin <9.0 g/dL, creatinine >2.4 mg/dL (male) or >2.0 mg/dL (female), calcium >12.0 mg/dL, platelet <100,000 /µL, neutrophil <1,500 /µL, nonclear-cell histology, and brain metastasis. RESULTS: Of 238 patients, 101 patients (42%) were determined as trial-ineligible. Progression-free survival (PFS) and overall survival (OS) after the TKI initiation were significantly shorter in the trial-ineligible patients than in the trial-eligible patients (median PFS: 5.53 vs. 15.8 months, p < 0.0001; OS: 13.8 vs. 43.4 months, p < 0.0001). Objective response rate was also significantly lower in the trial-ineligible patients (15% vs. 37%, p = 0.0003). Multivariate analysis further showed that the trial-eligibility was an independent factor for PFS (hazard ratio [HR]: 2.46, p < 0.0001) and OS (HR: 2.39, p < 0.0001). In addition, the number of trial-ineligible factors were negatively correlated with PFS and OS. CONCLUSIONS: In real-word, the substantial number of mRCC patients did not meet the trial-eligibility criteria, and their outcome was worse than that in the trial-eligible patients. Further studies focusing on the outcome in real-world trial-ineligible patients in the immune checkpoint inhibitor era are warranted.

"Thrombus-first" or "thrombus-last" approach for surgical management of renal cell carcinoma with inferior vena cava thrombus.

OBJECTIVES: To compare the perioperative outcomes between thrombectomy first then nephrectomy ("thrombus-first") and vice-versa ("thrombus-last") approaches for patients with renal cell carcinoma and inferior vena cava thrombus. METHODS: We retrospectively evaluated 130 patients who underwent nephrectomy and thrombectomy at two institutions between 1992 and 2020. The cohort was classified into the thrombus-first and thrombus-last groups according to the techniques used. Outcomes including the operative time, blood loss, and complications, especially the occurrence of intraoperative tumor embolism of pulmonary artery and postoperative pulmonary embolism, were compared. RESULTS: The thrombus-first and thrombus-last groups comprised 48 and 82 patients, respectively. Characteristics such as age, performance status, Charlson Comorbidity Index, renal function, and level of tumour thrombus were comparable between the two groups. Approximately 41% of the patients had distant metastasis. There were four cases (3.1%) of intraoperative tumor embolism, all from the thrombus-last group. Three patients overall (2.3%) experienced pulmonary embolism postoperatively with two in the thrombus-last group (2.4%) and one in the thrombus-first group (2.1%) (P > 0.999). The surgical time (291.0 min vs 369.0 min, P < 0.001) and the blood loss (1323.0 vs 2100.0 mL, P < 0.001) were significantly smaller for the thrombus-first group than for the thrombus-last group. Occurrence of complications was 25.0% and 43.9% in thrombus-first and thrombus-last groups, respectively (P = 0.029), and 8.3% and 23.2% for events graded ≥3 (P = 0.035). CONCLUSION: In surgery for renal cell carcinoma with inferior vena cava thrombus, performing thrombectomy before nephrectomy may serve to lessen complications, blood loss, and surgical time compared to nephrectomy before thrombectomy.

Robot-assisted laparoscopic versus open partial nephrectomy for renal cell carcinoma in patients with severe chronic kidney disease.

OBJECTIVES: To compare surgical and functional outcomes between robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy in patients with renal cell carcinoma with stage 4 chronic kidney disease. METHODS: This was a retrospective analysis of 60 patients with stage 4 chronic kidney disease (estimated glomerular filtration rate 15-30 ml/min/1.73 m2 ) who underwent partial nephrectomy for T1 renal cell carcinoma between April 2004 and April 2020. We compared perioperative outcomes according to the surgical approach. Multivariable analysis was performed to identify predictive factors for end-stage renal disease. RESULTS: Robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy were performed in 31 and 29 patients, respectively. The median age was 68 years and 17% of all patients were women. Patient and tumor characteristics did not differ between groups. The operative time (155.2 vs. 221.0 min, p < 0.0001) and the postoperative length of hospital stay (5.2 vs. 10.6 days, p = 0.0083) were significantly shorter, and the estimated blood loss was lower (53.4 vs. 363.2 ml, p = 0.0003) in the robot-assisted laparoscopic partial nephrectomy group than in the open partial nephrectomy group. Preoperative estimated glomerular filtration rate was the only significant predictor of end-stage renal disease after partial nephrectomy on multivariable analysis. CONCLUSIONS: Both procedures preserved renal function in this patient cohort, delaying the requirement for postoperative dialysis. Furthermore, robot-assisted laparoscopic partial nephrectomy was associated with shorter operative time and postoperative length of hospital stay, as well as lesser estimated blood loss than open partial nephrectomy.

Perioperative outcomes following robot-assisted partial nephrectomy for renal cell carcinoma according to surgeon generation.

OBJECTIVE: The experience of performing robot-assisted partial nephrectomy (RAPN) is associated with better surgical outcomes. However, surgeon's generation may impact surgical outcomes. We evaluated the perioperative outcomes of RAPN between first- and second-generation surgeons according to the surgeon's experience. METHODS: This study included 529 patients who underwent RAPN for renal cell carcinoma from January 2013 to November 2018. Four specific surgeons performed the surgery. According to the surgeon's generation, the patients were divided into two groups: first-generation and second-generation. To reflect the learning curve of RAPN, the surgical outcomes of each case (1-50, 51-100, 101-150) were evaluated between these groups. RESULTS: Between 1 to 50 cases and 101-150 cases, no significant differences in patient characteristics were observed between the two generations. Between 51-100 cases, age at surgery was significantly younger in the first-generation than in the second-generation group (58 years vs. 64 years, p = 0.04). The second-generation group had a shorter operation time in cases 1-50 (169 min vs. 188 min, p = 0.0001), 51-100 (145 min vs. 169 min, p = 0.008), and 101-150 (142 min vs. 165 min, p = 0.009), than the first-generation group. Although shorter WIT and higher trifecta achievement were observed in the second-generation group than in the first-generation group between 1-50 cases, the difference was not noted between 51-100 cases and 101-150 cases. CONCLUSION: Patients operated by second-generation surgeons had better surgical outcomes than first-generation surgeons, especially during the early experience period, which might result from their assistance experience, sophisticated surgical procedures refined by the first-generation, and the first-generation surgeon's introduction.