Surgical outcomes and predictive value for major complications of robot-assisted radical cystectomy of real-world data in a single institution in Japan.

OBJECTIVE: The objective of the study was to describe the surgical outcome of robot-assisted radical cystectomy and predictive factors for major complications in real-world clinical practice at a single institution in Japan. METHODS: We retrospectively analyzed 208 consecutive patients undergoing robot-assisted radical cystectomy at our institution between 2019 and 2023. Patient and disease characteristics, intraoperative details, and perioperative outcomes were reviewed. Postoperative complications were defined as minor complications (Clavien-Dindo grades 1-2) or major complications (grades 3-5). Predictors of complications were examined using multivariable logistic analysis. RESULTS: Overall, 147 men and 61 women, median age 70 years (interquartile range, 62-77), were included in this study. Median operative time and estimated blood loss were 8.4 h and 185 mL, respectively; 11 patients (5%) received intraoperative blood transfusions. For urinary diversions, ileal conduit, neobladder, and cutaneous ureterostomy were performed in 153 (74%), 49 (24%), and 6 (3%) patients, respectively. Urinary diversions were primarily performed with extracorporeal urinary diversion. In total, 140 complications occurred in 111 patients (53%) within 30 days. Of these patients, 31 major complications occurred in 28 patients, and one perioperative death (0.5%) with a postoperative cardiovascular event. Multivariable analysis showed only prolonged operative time (odds ratio: 4.34, 95% confidence interval: 1.82-10.35, p < 0.01) was the independent risk factor for major complications. CONCLUSIONS: This study reports surgical outcomes at our single institution. Prolonged operative time was a significant prognostic factor for major complications. As far as we know, this study reports the largest number of robot-assisted radical cystectomy cases at a single center in Japan.

A case of neoadjuvant chemotherapy-resistant muscle-invasive bladder cancer that markedly responded to pembrolizumab before conversion radical cystectomy.

Introduction: Recently, perioperative use of immune checkpoint inhibitors has improved the prognosis of muscle-invasive bladder cancer. It is unclear whether radical cystectomy or systemic pembrolizumab is the optimal next treatment in patients with muscle-invasive bladder cancer and progressive disease in the pelvic lymph node following neoadjuvant chemotherapy (NAC). Case presentation: A 62-year-old woman with cT3N0M0 bladder cancer and high programmed death-ligand 1 expression developed solitary obturator lymph node metastasis following 5 cycles of neoadjuvant chemotherapy. Six subsequent cycles of pembrolizumab shrank the lymph node significantly, and conversion radical cystectomy was planned. Pathologically, only carcinoma in situ around the scar of transurethral resection of bladder tumor remained in the primary tumor, and the accumulation of foamy macrophages and fibrosis without viable tumor cells was observed in the dissected lymph node. Eighteen months passed without a recurrence following radical cystectomy. Conclusion: Pembrolizumab administration before radical cystectomy achieved a good response in a patient with obturator lymph node metastasis following neoadjuvant chemotherapy.

TAS0313 plus Pembrolizumab for Post-Chemotherapy Immune Checkpoint Inhibitor-Naïve Locally Advanced or Metastatic Urothelial Carcinoma.

We evaluated the efficacy and safety of TAS0313, a multi-epitope long peptide vaccine, plus pembrolizumab in post-chemotherapy immune checkpoint inhibitor-naïve patients with locally advanced/metastatic urothelial carcinoma (la/mUC). TAS0313 9 mg was administered subcutaneously followed by pembrolizumab 200 mg on Day 1, and as monotherapy on Day 8 and 15 of Cycles 1 and 2, and Day 1 of subsequent cycles in 21-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarkers of response were assessed. In 36 patients enrolled, the ORR was 33.3% (complete response: 7 patients; partial response: 5 patients). Median PFS was 5.0 months; 6- and 12-month progression-free rates were 46.4% and 36.5%, respectively. Median OS was not reached; 6-, 12-, and 24-month OS rates were 83.3%, 72.2%, and 55.1%, respectively. In post hoc analysis, patients with a tumor infiltrating CD8+ lymphocyte (CD8+ TIL) count ≥99 and/or programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥50 and lymphocyte count >1,380 cells/µL had higher ORRs and prolonged PFS versus patients with a CD8+ TIL count <99, PD-L1 CPS <50, and lymphocyte count ≤1,380 cells/µL. Thirty-four (94.4%) patients receiving combination therapy experienced treatment-related adverse events (AE), with pyrexia (n = 15, 41.7%), injection-site reactions (n = 15, 41.7%), injection-site induration (n = 6, 16.7%), and malaise (n = 6, 16.7%) the most common. No grade ≥3 treatment-related AEs occurred in ≥10% of patients. TAS0313 plus pembrolizumab combination therapy showed promising efficacy and manageable safety in la/mUC. Clinical Trial Registration: JapicCTI-183824.

RAS Family Gene Mutations, Clinicopathological Features, and Spread Patterns of Inverted Urothelial Papilloma of the Bladder.

Inverted urothelial papilloma (IUP) is a benign neoplasm characterized by a downgrowth of the urothelium beneath the surface of morphologically normal urothelial cells; however, the molecular features of IUP and their association with clinicopathological characteristics are unclear. In this study, we aimed to investigate the mutational landscape, clinicopathological features, genotype-phenotype associations, and spread patterns of IUP. We performed targeted next-generation sequencing of 39 consecutive IUP cases, the largest series investigated to date, and identified oncogenic driver mutations in RAS family genes in 34 cases (87%). HRAS mutations were the most prevalent (28 cases), which included Q61R (15 cases), followed by KRAS (5 cases) and NRAS (1 case) mutations. Characteristic mutations observed in urothelial carcinoma, including those in FGFR3 , TP53 , or the TERT promoter, were absent. HRAS -mutated IUPs were associated with a history of smoking ( P = 0.017) and streaming morphology ( P < 0.001), corresponding to the trabecular subtype. In contrast, all KRAS -mutated IUPs occurred in never-smoking patients ( P = 0.001) and showed cystic changes in morphology ( P = 0.005), corresponding to the glandular subtype. RAS Q61R immunohistochemistry visually revealed the neoplastic nature of the overlying cells and distinct spread patterns of IUP cells within the surface, including pseudoinfiltrative spread. No recurrence or carcinoma development was observed in any of the IUP cases during the follow-up period. Thus, we confirmed the importance of RAS pathway activation in IUP pathogenesis, an association between RAS family gene mutations and IUP subtypes, and the spread patterns of IUP cells within the surface.

A case of sequential medical therapy for advanced ureteral cancer in Li-Fraumeni syndrome.

Introduction: Li-Fraumeni syndrome, an autosomal dominant cancer predisposition syndrome caused by a pathogenic variant of TP53, a tumor suppressor gene, leads to a high risk from early childhood of developing various types of cancers. Here, we report a case of advanced ureteral cancer in Li-Fraumeni syndrome. Case presentation: A 73 years-old female patient, who had been diagnosed genetically as Li-Fraumeni syndrome; suffered from chondrosarcoma in the left pelvic joint, bilateral breast cancer, endometrial cancer, gastric cancer, and colon cancer in her history. She was diagnosed as unresectable advanced urothelial cancer during continuous magnetic resonance imaging surveillance, underwent avelumab maintenance therapy after the combination of gemcitabine and cisplatin chemotherapy. The efficacies of gemcitabine and cisplatin chemotherapy and avelumab maintenance therapy were good. Conclusion: We report an advanced urothelial cancer in a patient with Li-Fraumeni syndrome who demonstrated good efficacies to sequential medical therapy.

CDX2- and PAX8-Expressing Subtypes in Female Urethral Adenocarcinoma: Pathogenesis Insights through Immunohistochemical and Morphological Analyses.

Female urethral adenocarcinoma has attracted attention as a rare tumor type based on its differential pathogenesis from its male counterpart. However, to date, our knowledge concerning its immunohistochemical and morphological characteristics remains limited due to the small number of cases studied. In this study, nine consecutive cases of female urethral adenocarcinoma were used for immunohistochemical and morphological characterization of the tumor based on semi-comprehensive immunohistochemical analysis and detailed morphological evaluations. Our immunohistochemical assay revealed two subtypes of female urethral adenocarcinoma with distinctive staining patterns: the CDX2- and PAX8-expressing subtypes. The former stained positive for other intestinal markers (e.g., HNF4α and TFF1) as well (7 of 7 cases); the latter stained negative for these intestinal markers (0 of 2 cases) but stained positive for clear cell carcinoma markers (e.g., Napsin A and HNF1ß) (2 of 2 cases). Regarding cytokeratins, the former displayed a CK7- and CK20-positive immunoprofile (7 of 7 cases); the latter exhibited a CK7-positive and CK20-negative immunoprofile (2 of 2 cases). Morphologically, CDX2- and PAX8-expressing subtypes resembled intestinal-type adenocarcinoma and clear cell carcinoma (occurring in gynecological organs), respectively. The semi-comprehensive immunoprofiling data presented in this study can potentially contribute to the correct diagnosis of this rare tumor type. Finally, our study represents an important basis for future investigations aiming to further elucidate the details and origin of female urethral adenocarcinoma, and it can potentially contribute to developing diagnostic and therapeutic strategies for treating this malignancy.

Prognostic Significance of Immune-related Adverse Events in Metastatic Renal Cell Carcinoma Patients Treated With Immune-checkpoint-inhibitors.

BACKGROUND/AIM: Immune-related adverse events (irAEs) develop in a subset of patients with metastatic renal cell carcinoma (mRCC) treated with immune-checkpoint-inhibitors (ICIs). Evidence regarding the prognostic impact of irAEs remains limited in these patients. PATIENTS AND METHODS: Ninety-one consecutive patients with mRCC treated with ICIs were retrospectively analyzed. Overall survival (OS) rates were estimated using the Kaplan-Meier method. In multivariate analysis, predictors of OS were analyzed using the Cox-proportional-hazards-model. RESULTS: Twenty-nine patients were treated with the combination of nivolumab plus ipilimumab. According to International Metastatic RCC Database Consortium risk classification, 27/47/17 patients were classified into favorable/intermediate/poor risk categories. The 1, 3, and 5-year OS-rates were 89, 70, and 57%, respectively. A total of 67 irAEs occurred in 44 patients (48%), including 15 patients with grade 3-4. OS was significantly longer in patients with irAEs (p=0.01). In multivariate analysis, Karnofsky performance status, prior nephrectomy, and irAEs were independent significant predictors of OS. CONCLUSION: In our study, irAEs were significantly associated with OS in mRCC patients treated with ICIs.

Real-world effectiveness of nivolumab and subsequent therapy in Japanese patients with metastatic renal cell carcinoma (POST-NIVO study): 36-month follow-up results of a clinical chart review.

OBJECTIVES: To examine the long-term effectiveness of nivolumab monotherapy and following subsequent therapies for metastatic renal cell carcinoma (mRCC) in Japanese real-world settings. METHODS: This was a multicenter, retrospective, observational study, with a 36-month follow-up, and conducted in Japanese patients with mRCC who initiated nivolumab monotherapy between 1 Feb 2017 and 31 Oct 2017. Endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: Of the 208 patients, 36.5% received nivolumab monotherapy as second-line, 30.8% as third-line, and 31.7% as fourth- or later-line therapy. By 36 months, 12.0% of patients continued nivolumab monotherapy; 88.0% discontinued, mainly because of disease progression (66.7%). The median (m) OS was not reached irrespective of treatment line, with a 36-month OS rate of 54.3% (second-line, 57.4%; third-line, 52.6%; fourth- or later-line, 52.9%). The ORR was 24.2% and five patients achieved complete response. The OS from first-line therapy was 8.9 years. In the 95 patients receiving therapy after nivolumab, 87.4% received vascular endothelial growth factor receptor-tyrosine kinase inhibitors, with mOS and mPFS of 27.4 and 8.1 months, respectively. Irrespective of treatment line, the mOS was not reached in patients with International Metastatic RCC Database Consortium (IMDC) favorable or intermediate risk at mRCC diagnosis. CONCLUSIONS: This 36-month real-world follow-up analysis showed a survival benefit of nivolumab monotherapy for patients with mRCC. The long-term effectiveness of sequential therapy from first-line therapy to therapy after nivolumab was also demonstrated. Additionally, nivolumab monotherapy was beneficial for patients with favorable IMDC risk at the time of mRCC diagnosis.

A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL).

BACKGROUND: The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases. METHODS: This phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI. DISCUSSION: This will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone. Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358.

Intensity-modulated radiation therapy for intermediate-risk prostate cancer: does ADT still have an impact in the dose-escalated external beam radiation therapy era?

BACKGROUND: This study aimed to investigate the effect of androgen deprivation therapy (ADT) on the survival of intermediate-risk prostate cancer (IR-PCA) patients treated with dose-escalated external beam radiation therapy (DE-EBRT), and to determine the group that will benefit from ADT. METHODS: We analysed 620 IR-PCA patients treated with DE-EBRT at two institutions. Variables were adjusted using the stabilised inverse probability of treatment weighting method (sIPTW) between radiation therapy (RT) and RT plus ADT groups. Biochemical relapse-free survival (bRFS) rate and overall survival (OS) rate were compared using Kaplan-Meier analysis and log-rank test. Cox proportional hazard analysis (CPH) was conducted to detect unfavorable risk factors. RESULTS: This study included 405 patients; with 217 and 188 patients in the RT and RT plus ADT groups, respectively. The prescribed radiation dose was 78 Gy in 39 fractions. The median follow-up time was 82.0 months. After sIPTW-adjustment, 214.3 and 189.7 patients were assigned to the RT and RT plus ADT groups, respectively. The 7-year bRFS and OS were 89.3% and 94.6% in RT group and 92.3% and 91.0% in RT plus ADT group, respectively. Before and after sIPTW adjustment, no statistically significant differences were found in these endpoints between treatment groups. Multivariate CPH for bRFS revealed Gleason score (GS) 4 + 3 as an unfavorable risk factor, and ADT improved biochemical control of them. CONCLUSION: ADT may not always be effective in all Japanese IR-PCA patients treated with DE-EBRT, but it can improve biochemical control in patients with GS 4 + 3.

A radiological complete response to pembrolizumab in a patient with metastatic upper urinary tract urothelial cancer and Lynch syndrome.

Introduction: In Lynch syndrome, urothelial cancer is the third most common cancer, following colorectal and endometrial cancers. Little is known, however, about the efficacy of immune checkpoint inhibitors in the treatment of metastatic urothelial cancer in Lynch syndrome. Case presentation: A 49-year-old patient with metastatic urothelial cancer underwent pembrolizumab therapy after platinum-containing chemotherapy. The efficacy of the pembrolizumab therapy was good. Her lung and bone metastatic lesions disappeared in imaging studies and her back pain decreased dramatically. Pathogenic mutations of MSH2 and BRCA2 were found in the DNA extracted from her tumor, and subsequent genetic analysis confirmed the germline pathogenic variant of MSH2. As such, this case was genetically diagnosed as Lynch syndrome. Conclusion: We report metastatic urothelial cancer in a patient with Lynch syndrome who demonstrated a radiological complete response to pembrolizumab therapy. Accurate genetic diagnosis can provide useful information to both the patient and their relatives.

Geriatric Nutritional Risk Index as a Predictor of Prognosis in Metastatic Renal Cell Carcinoma Treated with Nivolumab.

BACKGROUND: 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. METHODS: 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. RESULTS: Thirteen and forty-three patients were classified with low (GNRI < 92) and high (GNRI ≥ 92) GNRI, respectively. Patients with low GNRI demonstrated significantly shorter OS (P = 0.0002) than those with high GNRI. In multivariate analysis, GNRI at the time of nivolumab (P = 0.008) was extracted as the predictor for OS in addition to Karnofsky performance status (KPS) (P = 0.016). Integration of the GNRI into the International Metastatic Renal Cell Cancer Database Consortium (IMDC) risk classification improved the c-index from 0.761 to 0.833 (combination of GNRI with IMDC risk classification) and to 0.778 (substitution of GNRI with KPS in IMDC risk classification). CONCLUSIONS: GNRI was a significant prognostic biomarker in mRCC patients receiving nivolumab.

Renal function outcome after selective bladder-preserving tetramodality therapy consisting of maximal transurethral resection, induction chemoradiotherapy and consolidative partial cystectomy in comparison with radical cystectomy for patients with muscle-invasive bladder cancer: a two-centre retrospective study.

OBJECTIVE: To compare renal function (RF) outcomes after bladder-preserving tetramodal therapy against muscle-invasive bladder cancer (MIBC) to those after radical cystectomy (RC). METHODS: This 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. RESULTS: The 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. CONCLUSIONS: RF 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.

Japanese subgroup analysis of EV-301: An open-label, randomized phase 3 study to evaluate enfortumab vedotin versus chemotherapy in subjects with previously treated locally advanced or metastatic urothelial carcinoma.

BACKGROUND: Enfortumab vedotin (EV) is an antibody-drug conjugate showing significant overall survival (OS) benefit versus chemotherapy for patients with previously treated locally advanced or metastatic urothelial carcinoma (la/mUC) in EV-301. This subgroup analysis was conducted to further analyze the efficacy and safety in a Japanese population. METHODS: In the open-label, phase 3 EV-301 trial, patients with la/mUC were randomized 1:1 to EV 1.25 mg/kg on Days 1, 8, and 15 for 28-day cycles or investigator-preselected standard chemotherapy (SC; docetaxel or paclitaxel for patients in Japan) on Day 1 of each 21-day cycle. Primary endpoint was OS and secondary efficacy endpoints included progression-free survival (PFS) and overall response rate (ORR). Safety/tolerability was also evaluated. RESULTS: As of the July 15, 2020 cut-off date for the interim analysis, the Japanese subgroup included 86 patients (EV: n = 36; SC: n = 50). Median OS was 15.18 months for EV and 10.55 months for SC (HR: 0.437 [95% CI: 0.209, 0.914]). Median PFS was 6.47 months for EV and 5.39 months for SC (HR: 0.464 [95% CI: 0.258, 0.835]). Confirmed ORR was 34.4% for EV and 21.3% for SC. A higher proportion of patients receiving SC versus EV had treatment-related adverse events (TRAEs; 97.9% vs. 91.7%, respectively), including grade ≥ 3 TRAEs (75.0% vs. 63.9%). CONCLUSIONS: This subgroup analysis confirmed that EV, with consistent efficacy and safety/tolerability in the EV-301 Japanese subgroup and overall study population, represents an important treatment option for previously treated patients with la/mUC.

Development of a New Two-Arm Transurethral Surgical System for En Bloc Resection of Bladder Tumor: A Preclinical Study.

Backgrounds and Objectives: To overcome the piecemeal nature of bladder tumor resection, en bloc resection of bladder tumor (ERBT) has been introduced. ERBT is difficult for surgeons to perform using the currently available system because it has only one arm. Herein, we aimed to develop a new transurethral surgical system to facilitate two-arm ERBT and to report the results of preclinical experiments using tumor phantoms. Methods: Initially, we aimed to develop a brand-new surgical system for ERBT but, after trial and error, we redirected our development to the creation of three elements: the left arm to grasp the tumor; the right arm to cut the tumor; and the system to operate the arms that can be attached to the existing surgical system (UES-40 SurgMaster® [Olympus Co. Ltd., Tokyo, Japan]). The current system was evaluated by performing simulated ERBTs using tumor phantoms made from konjac jelly. Results: Following the assembly of developed arms into the UES-40 SurgMaster, we conducted preliminary ERBTs. After performing several resections, we adopted a basket-shaped forceps as the left arm instead of grasping forceps and an arched electrode as the right arm. The two arms and single endoscope were placed in an equilateral triangle. We performed ERBT for the tumor phantoms that ranged from 0.5 to 2.0 cm without major redo. Conclusion: Herein, we introduced our development for two-arm ERBT. The current concept of "two-hand transurethral surgery" has the potential to be developed in future in vivo and clinical trials.

De novo large-cell neuroendocrine carcinoma of the prostate: A case report and literature review.

Introduction: Prostatic large-cell neuroendocrine carcinoma is poorly studied. Although several case reports are available, information on the clinicopathological characteristics of this disease is limited, particularly for the de novo (hormone-naive) type. Herein, we report an extremely rare de novo case of this disease with a good prognosis despite a multi-metastatic status. Case presentation: An 83-year-old male patient presented with a high serum prostate-specific antigen level and was found to have de novo prostatic large-cell neuroendocrine carcinoma with an adenocarcinoma component upon pathological examination. Diagnosed with stage pT4cN1cM1c, he underwent chemo-hormonal therapy using a luteinizing hormone-releasing hormone antagonist and combined etoposide and cisplatin, which achieved a partial response. The patient has survived for 20 months without progression. Conclusion: Although prostatic large-cell neuroendocrine carcinoma is known for its aggressive clinical behavior, the de novo type with an adenocarcinoma component may be sensitive to hormonal therapy and achieve a good prognosis.

Tumor shrinkage patterns of nivolumab monotherapy in metastatic renal cell carcinoma.

OBJECTIVES: To investigate the tumor shrinkage patterns of patients with metastatic renal cell carcinoma treated with nivolumab monotherapy. METHODS: Forty-four consecutive patients with metastatic renal cell carcinoma treated with nivolumab monotherapy (81 metastatic and four primary lesions) between September 2013 and December 2020 were retrospectively analyzed. The tumor shrinkage rate of individual visceral and lymph node metastatic lesions and the primary site lesions treated with nivolumab monotherapy, as well as the association between overall survival and pretreatment tumor size, were statistically assessed. RESULTS: Pretreatment tumor size for the total and individual target lesions, which included kidneys, lungs, pancreas, and lymph nodes, were not correlated with tumor shrinkage rate. The tumor shrinkage rate was found to have no significant association with pretreatment tumor size between any organ. In addition, there is no significant difference in tumor shrinkage rate between larger (>median value) and smaller (

Improvement of Medical Treatment in Japanese Patients With Metastatic Renal Cell Carcinoma.

Background/Aim: To evaluate the relationship between treatment period and overall survival (OS) and to identify clinical factors associated with OS in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods: Two hundred thirteen consecutive patients with mRCC receiving systemic therapy between 2008 and 2020 were divided into two groups: those starting first-line therapy in 2008-2015 (n=133) and those in 2016-2020 (n=80). Clinical factors associated with OS were retrospectively and statistically analyzed. Results: Median OS and one-, three- and five-year OS rates were not reached and 88.7%, 64.9%, and 64.9% in patients treated in 2016-2020; 31.4 months and 78.5%, 42.8% and 34.2% in 2008-2015 (p=0.0013). Multivariate analysis identified the period in which first-line therapy was started as the strongest predictor for OS (p=0.0002). Conclusion: OS was significantly better in mRCC patients treated in 2016-2020 than in 2008-2015. Treatment period was the strongest predictor for OS.