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The Geriatric Nutritional Risk Index (GNRI) has been reported as a screening tool to assess the nutrition-related risk with mortality in older patients and those with the various diseases. However, the prognostic value of GNRI in metastatic renal cell carcinoma (mRCC) patients receiving nivolumab therapy remains unclear.Fifty-six consecutive patients with mRCC receiving nivolumab between September 2013 and August 2020 at our institution were retrospectively analyzed. The survival outcomes and prognostic factors associated with overall survival (OS) were statistically analyzed.Thirteen and forty-three patients were classified with low (GNRI92) and high (GNRI ≥ 92) GNRI, respectively. Patients with low GNRI demonstrated significantly shorter OS (GNRI was a significant prognostic biomarker in mRCC patients receiving nivolumab.

In order to search for predictive biomarkers of efficacy of pembrolizumab therapy for metastatic urothelial cancer (UC), we investigated the relationship between treatment outcomes and early neutrophil-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and C-reactive protein (CRP) responses.Medical records of 101 patients with metastatic UC who started pembrolizumab as a second-line or later treatment were reviewed. NLR, LDH, and CRP were recorded after 3 weeks of therapy. In addition, we investigated whether these factors had an association with prolonged progression-free (PFS) or overall (OS) survival.The objective response rate, median PFS, and median OS were 25.7%, 6.3 months, and 15.2 months, respectively. PFS and OS were significantly shorter in patients with NLR3, LDHupper limit of normal (ULN), and CRP0.5 mg/dl after 3 weeks of pembrolizumab treatment (p0.05). A predictive model comprising these factors (favorable risk group: 0 risk factors; intermediate-risk group: 1-2 risk factors; poor-risk group: 3 risk factors) revealed distinct PFS and OS curves (p0.001). In the favorable risk group, 12-month OS was 79.6%; in the poor-risk group, it was 12.8%. Harrell's C-indices for NLR3, LDHULN, CRP0.5 mg/dl, and all three combined for predicting OS were 0.656, 0.625, 0.633 and 0.678, respectively. Early responses were also non-significantly associated with ORR (p=0.37).Pembrolizumab treatment outcomes are associated with early NLR, LDH, and CRP responses in metastatic urothelial cancer.

Despite the rapid introduction of androgen receptor-targeted agents (ARTA) into clinical practice for castration-resistant prostate cancer (CRPC), the optimal treatment strategy after first-line ARTA remains unclear. The object of this study was to clarify clinical outcomes of second-line therapy for CRPC after first-line ARTA.The medical records of 130 consecutive patients with CRPC with disease progression during first-line ARTA and who started second-line therapy at our Institution between 2014 and 2020 were analyzed.A total of 130 patients with CRPC were identified. Ninety patients underwent ARTA-ARTA treatment, and 40 patients underwent ARTA-docetaxel treatment. The median observation period after second-line ARTA or docetaxel administration was 14.2 months. The prostate-specific antigen response rates overall, and after second-line ARTA, and docetaxel were 26.8%, 24.7%, and 31.6%, respectively. The median progression-free survival (PFS) and 1- and 2-year PFS rates of second-line therapy were 7.9 months and 34.6% and 15.4%, respectively. The median overall survival (OS) and 1- and 2-year OS rates were 27.4 months and 81.8%, and 54.9%, respectively. Multivariate analyses for OS disclosed that a C-reactive protein over the upper limit of normal and time from first-line ARTA to progression under 12 months were associated with shorter OS. Prostate-specific antigen response, PFS and OS of second-line therapy were not significantly different between second-line ARTA and docetaxel.There was no significant difference in OS between ARTA-ARTA and ARTA-docetaxel groups in the present study, suggesting that second-line ARTA might be the preferred treatment after initial failure of ARTA.

Prostate cancer localization is reportedly associated with the laterality of lymph node metastasis. Thus, it may be feasible to predict side-specific lymph node metastasis (LNM) at radical prostatectomy (RP). To investigate whether multiparametric magnetic resonance imaging and biopsy findings can predict side-specific negative LNM and to explore the feasibility of unilateral lymph node dissection (LND) at RP.A total of 500 patients who were diagnosed with prostate cancer with prebiopsy multiparametric magnetic resonance imaging of the prostate and subsequent prostate biopsy and who underwent RP and extended LND without neoadjuvant treatment were enrolled. Multiparametric magnetic resonance imaging, biopsy findings, and LNM were assessed for each side. The negative predictive value (NPV) of multiparametric magnetic resonance imaging or biopsy or both for ipsilateral LNM was examined.LNM was found in 9.2% (46/500) and 15.6% (28/180) of patients in the overall and high-risk cohorts, respectively. Magnetic resonance imaging and biopsy findings were negative in 408 and 262 sides, respectively, in the overall cohort and 144 and 100 sides, respectively, in the high-risk cohort. The NPVs of magnetic resonance imaging, biopsy, and both for ipsilateral LNM were 98.3%, 98.5%, and 99.1%, respectively, in the overall cohort, and 95.8%, 97.1%, and 97.6%, respectively, in the high-risk cohort.Unilateral LND may be indicated based on side-specific LNM risk as assessed by prebiopsy multiparametric magnetic resonance imaging and biopsy.

ObjectiveTo compare renal function (RF) outcomes after bladder-preserving tetramodal therapy against muscle-invasive bladder cancer (MIBC) to those after radical cystectomy (RC).MethodsThis study included 95 patients treated with tetramodal therapy consisting of transurethral bladder tumour resection, chemoradiotherapy and partial cystectomy (PC) and 300 patients treated with RC. The annual change in the estimated glomerular filtration rate (eGFR) was compared using the linear mixed model. Renal impairment was defined as a >25% decrease from the pretreatment eGFR, and renal impairment-free survival (RIFS) was calculated. The association between treatment type and renal impairment was assessed.ResultsThe number of patients who received neoadjuvant chemotherapy was 8 (8.4%) in the tetramodal therapy group and 75 (25.0%) in the RC group. After the inverse probability of treatment weighting adjustments, the baseline characteristics were balanced between the treatment groups. The mean eGFR before treatment in tetramodal therapy and RC groups was 69.4 and 69.6 mL/min/1.73 m2 and declined with a slope of −0.7 and −1.5 mL/min/1.73 m2/year, respectively. The annual deterioration rate of post-treatment eGFR in the tetramodal therapy group was milder than in the RC group. The 5-year RIFS rate in the tetramodal therapy and the RC groups was 91.2 and 85.2%, respectively. Tetramodal therapy was an independent factor of better RIFS compared with RC.ConclusionsRF was better preserved after tetramodal therapy than after radical therapy; however, even after tetramodal therapy, the eGFR decreased, and a non-negligible proportion of patients developed renal impairment.

In this study, we investigated the association between the early response of serum and hematological variables and the outcome of cabazitaxel therapy. The medical records of 59 consecutive patients who had previously received docetaxel chemotherapy for the treatment of metastatic castration-resistant prostate cancer (CRPC) and who received cabazitaxel at our hospital between January 2011 and March 2020 were retrospectively reviewed and statistically analyzed. The median follow-up period after cabazitaxel initiation was 15.2 months. The 30% prostate-specific antigen (PSA) response rate, median PSA progression-free survival period, and overall survival (OS) period were 45.8%, 4.3 months, and 22.6 months, respectively. Within 1 to 2 cycles of cabazitaxel, we were unable to identify hematological or serum kinetics that had a relationship with OS. Analysis of the variables after 3 cycles of cabazitaxel, however, revealed two factors, PSA decline > 30% (p = 0.016) and neutrophil–lymphocyte ratio (NLR) decline > 30% (p = 0.044), as the predictors of favorable outcome for OS. We established a prognostic model for predicting the OS period composed of these two factors, which exhibited distinctly separated OS curves (p = 0.004). The C-index of a model incorporating these two factors was 0.703. This is the first study to demonstrate that PSA and NLR decline 3 cycles after the initiation of cabazitaxel were associated with favorable outcome in patients with CRPC. Also, 3 cycles of cabazitaxel might be necessary to assess the efficacy of cabazitaxel therapy.

The value of the Vesicle Imaging-Reporting and Data System (VI-RADS) in the diagnosis of muscle-invasive bladder cancer (MIBC) for urothelial carcinoma with variant histology (VUC) remains unknown. We retrospectively evaluated 360 consecutive patients with bladder cancer (255 pure urothelial carcinoma [PUC] and 69 VUC) who underwent multiparametric magnetic resonance imaging between 2011 and 2019. VI-RADS scores assigned by four readers were significantly higher for the VUC group than for the PUC group (p0.05). In the cohort of 122 pair-matched patients, there was no significant difference in VI-RADS score distribution between the PUC and VUC groups for all readers (p 0.05). The area under the receiver operating characteristic curve for MIBC diagnosis via overall VI-RADS score was 0.93-0.94 for PUC and 0.89-0.92 for VUC, with no significant difference between the PUC and VUC groups (p = 0.32-0.60). These data suggests that VI-RADS scores achieved high diagnostic performance for detection of muscle invasion in both PUC and VUC. PATIENT SUMMARY: The Vesical Imaging-Reporting and Data System (VI-RADS) is a standardized system for reporting on detection of muscle-invasive bladder cancer via magnetic resonance imaging (MRI) scans. Our study shows that VI-RADS is also highly accurate for diagnosis for different variants of muscle-invasive bladder cancer, with good inter-reader agreement.

Enzalutamide is a novel, non-steroidal anti-androgen that has demonstrated excellent anti-tumor activity for both non-metastatic and metastatic castration-resistant prostate cancer (nmCRPC and mCRPC) patients, and that is being rapidly introduced into clinical practice in Japan.We retrospectively investigated the treatment efficacy, safety profile, and prognostic factors of enzalutamide over a relatively long observation period in Japanese patients with nmCRPC and mCRPC.The medical records of 184 consecutive Japanese patients with nmCRPC and mCRPC who started enzalutamide treatment in our institution between January 2012 and April 2018 were reviewed. Efficacy and safety profiles were assessed and statistically analyzed.Among these 184 patients, 44 (23.9%) nmCRPC patients, 89 (48.4%) docetaxel-naïve mCRPC patients, and 51 docetaxel-pretreated (27.7%) mCRPC patients underwent enzalutamide therapy. The median prostate-specific antigen progression-free survival (PSA-PFS) and overall survival (OS) periods for nmCRPC patients were 39.2 months and not reached; those for docetaxel-naïve mCRPC patients were 16.5 months and 59.8 months; and those for docetaxel-pretreated mCRPC patients were 7.0 months and 30.4 months, respectively. Multivariate analysis identified performance status ≥ 2, PSA 8.89 ng/mL (median value), hemoglobin lower limit of normal range, neutrophil to lymphocyte ratio 3.0, and 4-week PSA decline 50% as the predictive factors for shorter OS. Our respective prognostic models using these factors successfully demonstrated distinctly separated survival curves (p 0.001). In addition, among these patients, 30 (16.3%) experienced adverse events and 16 (8.7%) experienced adverse events resulting in the discontinuation of therapy. Fatigue (14%) and appetite loss (7%) were the most common such events.Both the survival period and risk factors were extracted from a relatively long-term observation period. Since enzalutamide was approved for administration to patients with castration-sensitive prostate cancer earlier this year (2020), we believe that the data presented here will be useful for both physicians and patients in clinical practice.

Background The paradigm of medical treatment for metastatic urothelial carcinoma is dramatically changing through the introduction of pembrolizumab. Aim We investigated the treatment effectiveness, the safety profile, and the prognostic factors of pembrolizumab in Japanese real‐world clinical practice. Methods and results The medical records of 74 consecutive Japanese patients with metastatic urothelial cancer (UC), who started pembrolizumab as a second‐ or later‐line treatment at our institution between January 2018 and March 2020, were reviewed and statistically analyzed. The median follow‐up period after initiation of pembrolizumab was 8.5 (interquartile range: 3.5–15.7) months. The objective response rate was 30.2%, the median progression‐free survival period was 4.9 months, and the median overall survival (OS) period was 13.3 months. Evaluation revealed that 39 (52.9%) patients experienced adverse events (AEs), among whom eight patients (10.9%) had severe AEs (grade 3 or more), including grade 5 hemophagocytic syndrome. Multivariate analysis indicated that the presence of liver metastasis, worse performance status (≥2), elevated serum lactate dehydrogenase, and increased C‐reactive protein were predictive of shorter OS. Conclusion We studied the effectiveness and safety profile of pembrolizumab therapy in Japanese UC patients. We believe that the data presented here will be useful for clinical physicians.

Currently, only a few reports exist on the cytokine release syndrome (CRS) as one of the severe immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Notably, it is very rare that grade 4 CRS related to ICI therapy overlaps with the drug-induced hypersensitivity syndrome (DiHS). A 46-year old woman with metastatic kidney cancer had grade 3 interstitial pneumonitis induced by four cycles of combination therapy of anti-programmed death-1 and anti-cytotoxic T lymphocyte-4 antibodies after right cytoreductive nephrectomy. Prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) was started concomitantly with prednisolone therapy to treat the interstitial pneumonitis. She developed hypotensive shock when reducing the dosage of prednisolone, and required intubation and ventilation using vasopressors at the intensive care unit. She subsequently exhibited prominent leukocytosis and an increased level of C-reactive protein, suggesting markedly increased cytokine levels. Interestingly, facial edema and erythema increased in association with pyrexia, leukocytosis, liver dysfunction, and renal failure, suggesting that she developed DiHS. She received hemodialysis three times, a plasma exchange, and anti-interleukin-6 therapy to treat severe renal dysfunction, a thrombotic thrombocytopenic purpura-suspected condition, and possible grade 4 CRS, respectively. Although these therapies did not elicit sufficient effects, high-dose administration of intravenous immunoglobulin was successful. With steroid mini-pulse therapy and the subsequent administration of prednisolone, she recovered successfully. To the best of our knowledge, this is the first report that ICIs and TMP/SMX can induce hypotensive shock accompanied with CRS and DiHS during immunosuppressive therapy for an irAE. Importantly, the prophylactic administration of TMP/SMX should be performed cautiously to avoid severe drug reactions such as CRS or DiHS.

Background We aimed to establish an external validation of the Briganti 2019 nomogram in a Japanese cohort to preoperatively evaluate the probability of lymph node invasion in patients with high-risk, clinically localized prostate cancer. Methods The cohort consisted of 278 patients with prostate cancer diagnosed using magnetic resonance imaging-targeted biopsy who underwent radical prostatectomy and extended pelvic lymph node dissection from 2012 to 2020. Patients were rated using the Briganti 2019 nomogram, which evaluates the probability of lymph node invasion. We used the area under curve of the receiver operating characteristic analysis to quantify the accuracy of the nomogram. Results Nineteen (6.8%) patients had lymph node invasion. The median number of lymph nodes removed was 18. The area under the curve for the Briganti 2019 was 0.71. When the cutoff was set at 7%, 84 (30.2%) patients with extended pelvic lymph node dissection could be omitted, and only 1 (1.2%) patient with lymph node invasion would be missed. Sensitivity, specificity, and negative predictive values at the 7% cutoff were 94.7, 32.0, and 98.8%, respectively. Conclusion This external validation showed that the Briganti 2019 nomogram was accurate, although there may still be scope for individual adjustments.

OBJECTIVES To evaluate the efficacy and safety profiles of first-line etoposide, ifosfamide and cisplatin and primary prophylaxis with pegfilgrastim as first-line chemotherapy for disseminated germ cell cancer. METHODS This study reviewed 154 consecutive patients with previously untreated disseminated germ cell cancer who received first-line etoposide, ifosfamide and cisplatin between 1995 and 2020. Of these, 54 patients were managed with primary prophylaxis using pegfilgrastim (primary prophylaxis group), and 100 were managed with the therapeutic use of short-acting granulocyte colony-stimulating factor (non-primary prophylaxis group). RESULTS The International Germ Cell Cancer Collaborative Group classification identified 90 (58%)/40 (26%)/24 (16%) patients with good/intermediate/poor prognosis, respectively. Overall, 139 patients (90%) were disease free after etoposide, ifosfamide and cisplatin with/without post-chemotherapy surgery. The median relative dose intensity of etoposide, ifosfamide and cisplatin was 96%, and there was a significant difference between the primary prophylaxis and non-primary prophylaxis groups (100% vs 90%, P

The modified Glasgow prognostic score (mGPS), which incorporates serum albumin and C-reactive protein levels, reflects systemic inflammation and nutritional status. In this study, we evaluate the role of mGPS as a predictor of prognosis in metastatic renal cell carcinoma treated with nivolumab.Forty-five consecutive patients with metastatic renal cell carcinoma receiving nivolumab therapy after tyrosine kinase inhibitor therapy between September 2013 and August 2019 at our institution were retrospectively analyzed. The prognostic factors associated with overall survival were statistically analyzed.The median follow-up period was 26.4 months. The median progression-free survival and 1- and 3-year progression-free survival rates were 11.6 months, 48.9%, and 17.1%, respectively. The median overall survival and 1- and 3-year overall survival rates were not reached, 88.7%, and 62.3%, respectively. In multivariate analysis, mGPS at the time of nivolumab administration (P .0001; hazard ratio [HR], 95.7; P = .0004 [Score 1 vs. 0]; HR, 98.9; P = .0002 [Score 2 vs. 0]; and HR, 1.03; P = .971 [Score 2 vs. 1]) was extracted as the strongest predictor for overall survival followed by duration from diagnosis to treatment (P = .0001), lactate dehydrogenase (P = .0005), and lymphocyte count (P = .021). Overall survival curves were distinctly separated between mGPS Score 0 and mGPS Score 1 + 2, with median overall survival periods being not reached and 32.4 months, respectively (P = .0004).mGPS was the strongest significant prognostic biomarker in patients with metastatic renal cell carcinoma treated with nivolumab. This simple classification could be useful in clinical practice.

Background Second-line salvage therapy for patients with metastatic germ-cell cancer (GCC) after the first-line combination of VIP (etoposide, ifosfamide, cisplatin) therapy has not been established. This study evaluated the efficacy and tolerability of the TGP (paclitaxel, gemcitabine, cisplatin) combination chemotherapy as a second-line salvage therapy. Patients and Methods The medical records of 16 consecutive patients with metastatic GCC who had been treated with first-line VIP therapy followed by second-line TGP therapy between 2005 and 2019 were reviewed and statistically analyzed. Ten patients, excluding the 6 patients treated with TGP without unequivocal progression, were included in the efficacy analysis. All 16 patients were included in the safety analysis. Results The median follow-up period from initial TGP administration was 78 months (interquartile range, 46-120 months). The estimated 5-year progression-free and overall survival rates for the 10 patients in the efficacy analysis were 70% and 100%, respectively. Grade 3/4 hematologic toxicity occurred in all 16 patients, but none developed uncontrollable infections or life-threatening bleeding. One patient died of treatment-related secondary leukemia, however. Conclusion The present study is to our knowledge the first to examine the therapeutic outcomes and safety profile of second-line TGP chemotherapy. VIP followed by TGP might be an alternative first- and second-line conventional regimen for patients with metastatic GCC in this granulocyte colony-stimulating factor era, especially for patients at a high risk of bleomycin-induced pulmonary toxicity.

INTRODUCTION AND OBJECTIVES: Magnetic resonance imaging (MRI)-targeted prostate biopsy (MRBX) is an effective biopsy procedure for with suspicion of prostate cancer on MRI. However, some significant cancer (SC) is missed using MRBX. Use of systematic prostate biopsy (SBX) for negative areas on MRI to detect SC missed by MRBX is not established for this indication. In this study, we aimed to explore the optimal combination of SBX and MRBX in these patients. METHODS: Between 2014 and 2015 at our institution, 271 men underwent MRBX with or without SBX based on prebiopsy multiparametric 1.5T MRI. Of these, 52 were excluded from the analysis because of PSA levels>40 ng/ml, obvious clinical T3-4 disease or biopsy with an insufficient number of cores for severe comorbidity. The remaining 219 men who underwentMRBXandSBXinonesessionaccording toourbiopsyprotocolwere enrolled in this study. MRBX was performed under cognitive or MRI/transrectal ultrasound fusion. Using MRBX, four-core samples for one suspicious lesiononMRIwereperformed.TheSBXprotocolwasa transperineal18-core biopsy.SCwasdefinedasclinical stageT2borgreater,biopsyGleasonscore of 4+3orgreater, ormaximumcancer lengthof 5mmorgreater.Cancerother thanSCwasdefinedas indolent cancer (IC). SC thatwasnot detected or that wasdetectedas ICusingMRBX,but thatwasdetectedasSCusingSBXwas defined as MRBX-missed SC. The frequency of MRBX-missed SC was investigated. A SBX protocol that could sufficiently detect MRBX-missed SC with a minimum number of sampling cores was determined. RESULTS: The median PSA was 7.5 ng/ml, and one/two suspicious lesions were observed in 204/15 patients, respectively, using MRI. The detection rate of any cancer or SC using both MRBX and SBX was 76%or 61%, respectively. Frequency ofMRBX-missed SC to overall SC was 13% (21/135). MRBX results in MRBX-missed SC patients was no cancer in 8 and IC in 13. Of 21 MRBX-missed cancer, a maximum of 10, 13, 15, 17, 19, 20 and 21MRBX-missed SCwere detected using 2, 4, 6, 8, 10, 12and14SBXsamplingcores, respectively.Whenweset theSC detection rate using both MRBX and the transperineal 18-core SBX at 100%, aminimum of 6 sampling cores in SBX (in addition to MRBX) were required to detect 95% of overall SC as SC. The six SBX sampling locationswere bilateral transperineal anterior, posterior and far lateral sites. CONCLUSIONS: The combination of transperineal 6-core SBX and MRBX could be an optimal biopsy strategy that strikes a balance between SC detectability and sampling number for men with suspicion of prostate cancer on MRI.