Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort.

OBJECTIVE: Real-world evidence regarding enfortumab vedotin for unresectable or metastatic urothelial carcinoma is scarce, particularly in Japan. We investigated real-world data focusing on patient background, previous treatments, response, survival and adverse events in patients receiving enfortumab vedotin. METHODS: A multicentre database was used to register 556 patients diagnosed with metastatic urothelial carcinoma from 2008 to 2023; 34 patients (6.1%) treated with enfortumab vedotin were included. Best radiographic objective responses were evaluated using the Response Evaluation Criteria in Solid Tumors (v1.1) during treatments. Overall survival and progression-free survival were estimated (Kaplan-Meier method). Toxicities were reported according to the Common Terminology Criteria for Adverse Events, version 5.0. The relative dose intensity, which could impact oncological outcomes, was calculated. RESULTS: The median number of enfortumab vedotin therapy cycles was 5. The best objective response to enfortumab vedotin was partial response, stable disease and progressive disease in 19 (56%), 5 (15%) and 10 (29%) patients, respectively. The median overall survival and progression-free survival after the first enfortumab vedotin dose were 16 and 9 months, respectively. No significant relationship was observed between survival outcomes after enfortumab vedotin initiation and the enfortumab vedotin relative dose intensity. The median overall survival from first-line platinum-based chemotherapy initiation was 42 months. Twenty-six (76%) patients experienced any grade of enfortumab vedotin-related toxicities; eight (24%) experienced Grades 3-4 toxicities, the most common being skin toxicity (any grade, 47%; Grades 3-4, 12%). CONCLUSIONS: Here, we report real-world evidence for enfortumab vedotin therapy in Japan. Tumour responses and safety profiles were comparable with those of clinical trials on this novel treatment.

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study.

OBJECTIVE: To develop the first Japanese real-world evidence of switch-maintenance avelumab in advanced, unresectable or metastatic urothelial carcinoma (aUC). METHODS: A multicenter-derived database registered 505 patients diagnosed with aUC between 2008 and 2021. Of these, 204 patients (40%) were selected and stratified according to the type of therapy used: maintenance avelumab group (27 [5.3%]), second-line (2 L) pembrolizumab group (103 [20%]) and 2 L cytotoxic chemotherapy group (74 [15%]). The progression-free survival and overall survival from the initiation of following therapy were compared. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors guideline v1.1 during the treatment period. A detailed analysis was performed in the maintenance avelumab group to investigate possible factors associated with response to avelumab therapy. RESULTS: The maintenance avelumab group had a longer overall survival, not progression-free survival, compared with the other two treatment groups. The median treatment-free interval between the last dose of first-line (1 L) chemotherapy and the initiation of avelumab therapy was 6 weeks (range, 3-22). Disease control rate of maintenance avelumab therapy in patients with a treatment-free interval of ≤6 weeks was higher than that in patients with a treatment-free interval of >6 weeks (77 vs 40%, P = 0.029). The patients showing objective response to 1 L chemotherapy were less likely to experience tumor relapse (4 of 19) after the initiation of avelumab therapy compared with those showing stable disease (7 of 8). CONCLUSIONS: Objective response to 1 L chemotherapy and early induction of maintenance avelumab therapy may be associated with increased benefit from maintenance avelumab therapy.

[Adrenal Hemangiomatous Endothelial Cyst That was Difficult to Differentiate from Adrenal Malignant Tumor: A Case Report].

A 65-year-old woman was referred to our hospital for fever and diagnosed with pyelonephritis. Abdominal computed tomography showed a right adrenal tumor incidentally, that was 6.5 cm in diameter. We could not rule out malignant disease by magnetic resonance imaging examination and performed resection of the right adrenal tumor. The histopathological examination revealed an adrenal hemangiomatous endothelial cyst, and there was no evidence of malignancy. It was difficult to differentiate between adrenal cyst and adrenal cancer in preoperative diagnostic imaging because the tumor contained hemorrhage and necrotic tissue.

[Efficacy of Recombinant Thrombomodulin for Sepsis-Associated Disseminated Intravascular Coagulation Caused by Urinary Tract Infections].

Severe urinary tract infections occasionally cause sepsis and disseminated intravascular coagulation (DIC). We examined the efficacy of recombinant thrombomodulin (rTM) for treating DIC caused by urosepsis. We enrolled 40 patients who were diagnosed with DIC caused by urosepsis at our hospital between April 2018 and May 2022. Twenty-six patients were treated with rTM (rTM group), while 14 patients did not receive rTM (non-rTM group). The DIC score before treatment in the rTM group was significantly higher than that in the non-rTM group (P＜0.01). There was no significant difference in disease-specific survival between the two groups. There was a significant improvement in DIC scores on days 1-3 after administering rTM. However, the duration of DIC in the rTM group was significantly longer than that in the non-rTM group (P＝0.038). The administration of rTM may have benefits in patients with DIC caused by urosepsis.

[Management of Internal Ureteral Stent (Double J-Stent) Occlusion].

Occlusion of internal ureteral stents commonly called double-J (DJ) stent leads to renal dysfunction, urinary tract infection, and difficulty in replacing the stent. We investigated the cause of stent occlusion and whether DJ stent occlusion persisted with change in the type of stent. The internal ureteral stent, Bird® Inlay™ Optima or Boston Scientific® Tria™, was inserted in 43 ureters of 33 patients who underwent replacement more than three times between September 2017 and June 2020. We defined stent occlusion as follows: a guide wire could not be passed through a stent during the replacement. In the first occlusion, the type of stent was changed. In the second occlusion, the stent placement interval was shortened from 12-13 weeks to 6-8 weeks. The presence of urinary stone and insertion of a urethral catheter had a high risk of DJ stent occlusion. Stent occlusion was observed in 20 of the 43 ureters. After the type of stent in 20 ureters with stent occlusion was changed, there were no DJ stent occlusions in 16 of the 20 ureters. Nevertheless, in 4 of the 20 ureters, even if we changed the type, DJ stent occlusion was still present; hence, the replacement interval was shortened. Therefore, changing the type of stent may be a recommended intervention for DJ stent occlusion.

Optimal timing of ureteroscopic lithotripsy after the initial drainage treatment and risk factors for postoperative febrile urinary tract infection in patients with obstructive pyelonephritis: a retrospective study.

BACKGROUND: A history of preoperative obstructive pyelonephritis has been reported as a risk factor for febrile urinary tract infection (fUTI) after ureteroscopic lithotripsy (URSL). But there is no clear evidence of risk factors for developing fUTI including the optimal timing of URSL after obstructive pyelonephritis treatment. METHODS: Of the 1361 patients, who underwent URSL at our hospital from January 2011 to December 2017, 239 patients had a history of pre-URSL obstructive pyelonephritis. The risk factors were analyzed by comparing the patients' backgrounds with the presence or absence of fUTI after URSL. The factors examined were age, gender, body mass index, comorbidity, presence or absence of preoperative ureteral stent, stone position, stone laterality, stone size, Hounsfield unit (HU) value on computed tomography scan, history of sepsis during obstructive pyelonephritis, period from antipyresis to URSL, ureteral stenting period, operation time, and presence or absence of access sheath at URSL. In addition, the stone components and renal pelvic urinary culture bacterial species during pre-URSL pyelonephritis were also examined. RESULTS: Post-URSL fUTI developed in 32 of 239 patients (13.4%), and 11 of these 32 cases led to sepsis (34.4%). Univariate analysis showed that stone position, stone maximum HU value, presence of sepsis during obstructive pyelonephritis, period from antipyresis to URSL, pre-URSL ureteral stent placement, operation time were risk factors of fUTI. Stone components and urinary cultures during pyelonephritis were not associated with risk of fUTI. Multivariate analysis showed that renal stone position, pre-URSL ureteral stent placement > 21 days, and operation time > 75 min were independent risk factors of fUTI following the URSL. CONCLUSIONS: F-UTI following the URSL could be avoided by ureteral stent placement period 21 days or less and operation time 75 min or less in patients with obstructive pyelonephritis.

Supplementary granulocyte macrophage colony-stimulating factor to chemotherapy and programmed death-ligand 1 blockade decreases local recurrence after surgery in bladder cancer.

Despite advances and refinements in surgery and perioperative chemotherapy, there are still unmet medical needs with respect to radical cystectomy for muscle-invasive bladder cancer (MIBC). We investigated the potential benefit of supplementary granulocyte macrophage colony-stimulating factor (GM-CSF) to chemoimmunotherapy with programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis blockade and standard neoadjuvant chemotherapy in bladder cancer. We inoculated 2 × 105 MBT2 cells s.c. in C3H mice to create a syngeneic animal model of local recurrence (LR). When the tumor diameter reached 12 mm, the mice were allocated randomly as follows: (i) non-treated control (vehicle only); (ii) anti-mPD-L1 monotherapy; (iii) mGM-CSF monotherapy; (iv) anti-mPD-L1 plus mGM-CSF; (v) gemcitabine and cisplatin (GC); (vi) GC plus anti-mPD-L1; (vii) GC plus mGM-CSF; and (viii) GC plus anti-mPD-L1 plus mGM-CSF. After completing 2-week neoadjuvant therapy, tumors were resected for resection margin evaluation and immunohistochemical staining and blood was collected for flow cytometry and ELISA. Operative wounds were sutured, and the operative site was monitored to detect LR. Addition of anti-mPD-L1 and mGM-CSF to neoadjuvant GC chemotherapy enhanced the antitumor effect and reduced positive resection margins (50% vs 12.5%). Combination of GC, anti-mPD-L1, and mGM-CSF resulted in longer LR-free survival and cancer-specific survival compared to those in other groups. These effects involved an immunotherapy-related decrease in oncological properties such as tumor invasion capacity and epithelial-mesenchymal transition. mGM-CSF significantly decreased the accumulation of myeloid-derived suppressor cells in both the blood and tumor microenvironment and blood interleukin-6 levels. Supplementary GM-CSF to neoadjuvant GC plus PD-L1 blockade could decrease LR after radical surgery by immune modulation in the blood and tumor microenvironment.

Dual benefit of supplementary oral 5-aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model.

BACKGROUND: Normal tissue damage caused by radiotherapy remains the largest dose-limiting factor in radiotherapy for cancer. Therefore, the aim of this study was to investigate the supplementary oral 5-aminolevulinic acid (ALA) to standard radiation therapy as a novel radioprotective approach that would not compromise the antitumor effect of radiation in normal rectal and bladder mucosa in a syngenic prostate cancer (PCa) model. METHODS: To evaluate the radiosensitizing effect of ALA in vitro, clonogenic survival assays were performed in DU145, PC3, and MyC-CaP cell lines. To evaluate the effect of ALA in vivo a single dose (25 Gy) of radiation with or without ALA was given to healthy mice. Next, a syngenic PCa model of MyC-CaP cells in FVB mice was created, and multiple doses (12 Gy total) of radiation were administered to the mouse pelvic area with or without ALA administration. Resected tumors, recta, and urinary bladders were immunostained with antibodies against Ki-67, γ-H2AX, CD204, and uroplakin-III. Total RNA levels in recta and urinary bladders were analyzed via RT2 Profiler polymerase chain reaction (PCR) arrays related to "Stress & Toxicity PathwayFinder," "Mitochondria," and "Inflammasomes." RESULTS: The addition of in vitro single or in vivo repeated administration of exogenous ALA acted as a radiosensitizer for PCa cells. Rectal toxicity was characterized by histological changes including loss of surface epithelium, fibrosis, severe DNA damage, and the aggregation of M2 macrophages. Urinary bladder toxicity was characterized by bladder wall thickening and urothelium denuding. The higher dose (300 mg/kg/day) of ALA exerted a better radioprotective profile than the lower dose (30 mg/kg/day) in normal recta and urinary bladders. Out of the 252 genes tested, 35 (13.4%) were detected as relevant genes which may be involved in the radioprotective role of ALA administration. These included interleukin-1a (IL-1a), IL-1b, IL-12, chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL3, and NLRP3. CONCLUSIONS: Our study provides novel and comprehensive insights into the dual benefits including radiosensitizing PCa tumor tissues and radioprotection of normal pelvic organs from radiation therapy. Knowledge of the underlying mechanism will facilitate the search for optimal treatment parameters for supplemental oral ALA during radiotherapy for PCa.

Preoperative predictive factors focused on inflammation-, nutrition-, and muscle-status in patients with upper urinary tract urothelial carcinoma undergoing nephroureterectomy.

OBJECTIVE: The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with upper urinary tract urothelial carcinoma (UTUC) undergoing curative nephroureterectomy (NUx). METHODS: The study enrolled 125 patients and the preoperative variables assessed included age, body mass index, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), serum fibrinogen level (Fib), C-reactive protein (CRP), modified Glasgow prognostic score, serum albumin level (Alb), prognostic nutritional index (PNI), skeletal muscle index (SMI), psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables and their prognostic values after NUx were evaluated. RESULTS: Five inflammation markers (NLR, MLR, PLR, Fib and CRP) were positively correlated. Fib was positively correlated with NLR, PLR and CRP, but inversely correlated with SMI. PNI was inversely correlated with age and the four inflammation markers (p < 0.001). Age was not significantly correlated with the inflammation markers, but older age was associated with lower Alb, PNI, SMI, PMI, and PEF. Disease-specific survival was independently predicted by preoperative ipsilateral hydronephrosis and low PNI. Overall survival was independently associated with high Fib and low PNI. CONCLUSION: The preoperative inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for UTUC.

The diagnostic utility of retroperitoneoscopic tissue biopsy for unresectable retroperitoneal lesions excluding urogenital cancers.

BACKGROUND: Retroperitoneal tumors are an uncommon disease known to consist of a diverse group of benign and malignant neoplasms. Treatment of unresectable retroperitoneal lesions requires pathological diagnosis. Here, we report the utility and safety of retroperitoneoscopic biopsy for unresectable retroperitoneal lesions excluding urogenital cancers. METHODS: We analyzed 47 patients consisting of 23 (49%) and 24 (51%) cases that underwent retroperitoneoscopic tissue biopsy and open biopsy, respectively. The clinicopathological features, including postoperative complications, were compared between the two groups. RESULTS: Tumor pathology was diagnosed successfully with a single operation in all patients. Malignant pathology (68%) was more common than benign pathology (32%). The most common pathology was malignant lymphoma, which accounted for about 50% of all cases. There was no significant difference with respect to the age, sex, tumor size, presence of tumor-related symptom, histopathology, operative time, and complications. Three (13%) of 23 patients in the retroperitoneoscopic biopsy group received percutaneous needle biopsy before laparoscopic excisional biopsy because the evaluation of needle cores failed to confirm subclasses of diagnosed pathologies. One patient was converted to open surgery just after the initiation of operation due to severe adhesion of adjacent structures. We had two cases with iatrogenic urinoma due to ureteral injury after retroperitoneoscopic biopsy. CONCLUSIONS: We conclude that retroperitoneoscopic biopsy is a safe and useful tool for benign and malignant retroperitoneal lesions, in comparison to open biopsy. It is critical to carefully examine the preoperative imaging for the location of tumors, especially those close to the renal pelvis and ureter.

[Spontaneous Tumor Lysis Syndrome in a Patient with Testicular Malignant Lymphoma : A Case Report].

A 75-year-old man, highly suspected as having malignant lymphoma originating from his left testis, underwent exploratory orchiectomy for a definitive diagnosis. Laboratory examinations before the surgery showed high lactate dehydrogenase (652 IU/l), elevated serum creatinine level (1.85 mg/dl) and sIL-2R level (8,930 U/ml). As the postoperative course passed uneventfully, the patient was discharged from the hospital on the eighth day after the surgery. Ten days after the surgery the patient was transferred to the emergency room of the hospital complaining of severe abdominal pain and malaise. Laboratory examinations revealed highly elevated lactate dehydrogenase (2,807 IL/l), uric acid (24.9 mg/dl) and serum creatinine (5.31 mg/dl). Computed tomography demonstrated rapid growth of the retroperitoneal mass and occurrence of bilateral hydronephroses. Under the diagnosis of spontaneous tumor lysis syndrome, the patient was urgently treated with hemodialysis, steroidal pulse and rituximab following percutaneous nephrostomy for the right kidney. After improvement of the laboratory data, the patient was transferred to another hospital for the treatment of malignant lymphoma.

Clinical Features and Risk Factors of Skeletal-Related Events in Genitourinary Cancer Patients with Bone Metastasis: A Retrospective Analysis of Prostate Cancer, Renal Cell Carcinoma, and Urothelial Carcinoma.

OBJECTIVE: The objective of the present study was to report the incidence of skeletal-related events (SREs) and identify risk factors for SREs in patients with genitourinary cancer with newly diagnosed bone metastasis. METHODS: This retrospective study included 180 patients with bone metastasis from prostate cancer (PCa; n = 111), renal cell carcinoma (RCC; n = 43), and urothelial carcinoma (UC; n = 26). Clinical factors at the time of diagnosis of bone metastasis were evaluated with Cox proportional hazards regression analysis to identify independent risk factors for SREs. RESULTS: During follow-up, 29 (26%) patients with PCa, 30 (70%) with RCC, and 15 (58%) with UC developed SREs. Treatment with bone-modifying agents (BMAs) before the development of SREs and within 6 months from the diagnosis of bone metastasis significantly delayed the time to first SRE as compared to nonuse of BMAs. Multivariate analysis identified type of primary cancer (PCa vs. RCC, PCa vs. UC), performance status, and bone pain as significant independent predictive risk factors for SREs. CONCLUSIONS: Treatment with BMAs significantly delayed the development of first SREs. The identified predictors of SREs might be useful to select patients who would benefit most from early treatment with BMAs.

[Predictive Factors of Biochemical Recurrence in Positive Surgical Margin Patients by Radical Prostatectomy].

The predictive factors for biochemical recurrence (BCR) were investigated in patients with positive surgical margin of the extirpated prostate by radical retropubic prostatectomy (RRP). The records of 365 patients who underwent RRP in our hospital between January 2002 and December 2014 were retrospectively analyzed. Patients who had received additional therapy before or after RRP, who had not been followed up for more than a year after surgery, and who had pN1 lesions were excluded from the study. Positive surgical margin was observed in 112 cases. Prostate specific antigen (PSA) before surgery ≥20 ng/ml, biopsy positive core ratio ≥40%, Gleason score of the surgical specimen ≥8, and postoperative PSA nadir ≥0.01 ng/ml were identified as significant predictors of BCR.

[Predictive Factors of Positive Surgical Margin in Radical Prostatectomy].

To identify the predictive factors for positive surgical margin after radical prostatectomy, we retrospectively analyzed the records of 381 patients who underwent radical prostatectomy in our hospital between January 2002 and December 2014. Patients who had received hormonal therapy before surgery were excluded from the study. Positive surgical marginwas observed in121 cases (31.8%), and prostate specific antigen (PSA) before surgery ≧10 ng/ml (HR1.89 : 95%CI 1.17-3. 07) and BMI≧25 kg/m2 (HR2.73 : 95%CI 1.60-4. 68) were identified as significant predictors of positive surgical margin. The existence of PSM significantly correlated to the operation time of 240 minutes or longer (HR2.27 : 95%CI 1. 35-3.79), pT2c or higher local stage (HR2.08 : 95%CI 1.17-3.72) and 7 or higher Gleason score of the resected specimen(HR1.63 : 95%CI 1.03-2.59).

Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort.

The clinical significance of regulatory T cells (Treg) and tumor-associated macrophages (TAM) in the tumor microenvironment of human bladder cancer remains unclear. The aim of this study is to explore their relevance to oncological features in non-muscle invasive bladder cancer (NMIBC). We carried out immunohistochemical analysis of forkhead box P3 (FOXP3, Treg maker), CD204 (TAM marker), and interleukin-6 (IL6) using surgical specimens obtained from 154 NMIBC patients. The Treg and TAM counts surrounding the cancer lesion and IL6-positive cancer cell counts were evaluated against clinicopathological variables. We focused on the ability of the Treg and TAM counts around the cancer lesion to predict outcomes after adjuvant intravesical Bacille Calmette-Guérin (BCG) treatment. High Treg counts were associated with female patients, older age, T1 category, and high tumor grade. TAM count was significantly correlated with Treg count and with IL6-positive cancer cell count. In our analysis of 71 patients treated with BCG, high counts of Treg and TAM were associated with shorter recurrence-free survival, and the former was an independent predictor of recurrence. Poor response to intravesical BCG was associated with Treg and TAM in the tumor microenvironment. Disrupting the immune network can be a supplementary therapeutic approach for NMIBC patients receiving intravesical BCG.

[The efficacy of the use of acetic acid test in a case of local recurrence of penile carcinoma].

A 62-old-year male presented to our hospital with induration of the prepuce and bleeding from the glans penis that occurred during sexual intercourse. Scrape cytology was performed, which showed class V, suspected squamous cell carcinoma. Computed tomography showed no metastases, and magnetic resonance imaging revealed no invasion of the corpus spongiosum. Circumcision and resection of the glanstumor were performed. Histopathological examination revealed squamous cell carcinoma in situ. We diagnosed the case as penile carcinoma in situ (pTisN0M0, UICC stage 0, and Jackson stage I). At 6 months postoperatively, local recurrence of penile carcinoma was detected by visual inspection after 5% acetic acid staining, and tumor resection was performed. At 9 months postoperatively (after the 2nd resection), the patient has remained disease-free, with no evidence of recurrence.

[Case of inflammatory pseudotumor occurring in the renal pelvis].

Inflammatory pseudotumor most commonly involves the lung. However, inflammatory pseudotumor has been reported in various sites in the abdomen, including the kidneys, retroperitoneum and urinary tract. We present a rare case of pathologically proven inflammatory pseudotumor in the renal pelvis. A 45-year-old woman was referred to our hospital with gross hematuria. Computed tomography demonstrated a mass around the right renal pelvocalyceal system suggestive of cystic renal cell carcinoma. Retrogradepyelography was done. Pelvic urine cytology was class III. The possibility of urothelial carcinoma could not be denied. Retroperitoneoscopic nephroureterectomy with open bladder cuff excision was performed. The histological examination revealed an inflammatory pseudotumor. She showed no evidence of disease 44 months after the operation.

[Renal pelvic tumor with difficult radiological diagnosis : a report of two cases].

Case 1 : A 60-year-old man presented with right flank pain. A computed tomography (CT) scan revealed a large right renal tumor, multiple lung metastases, multiple liver metastases, and tumor thrombus of the right renal vein. These findings were strongly suggestive of renal cell carcinoma. The patient suddenly complained of dyspnea at night due to bilateral pulmonary embolism, and the patient died 11 days after onset. Needle necropsy showed that the tumors were squamous cell carcinomas of the renal pelvis. Case 2 : A 66-year-old man presented with macrohematuria. An abdominal CT scan revealed a right renal mass and liver metastasis. The differential diagnosis was between renal cell carcinoma and urothelial carcinoma. A renal biopsy revealed urothelial carcinoma of the renal pelvis. The patient died of the disease 3 months after initiation of chemotherapy with gemcitabine and cisplatin. We report these 2 cases to emphasize the importance of renal biopsy and thorough histological analysis for the determination of treatment strategies against unresectable renal tumors.

Impact of Complete Surgical Resection of Metastatic Lesions in Patients with Advanced Renal Cell Carcinoma in the Era of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors.

Complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) has demonstrated efficacy in the cytokine era, but its effectiveness in the era of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) remains unclear. A multi-institutional database included clinicopathological data of 367 patients with mRCC. Patients were divided into two groups: the CM group and the non-CM group. These two groups were compared before and after propensity score matching (PSM). Cox proportional hazard models were used to detect factors associated with disease-free survival (DFS) and overall survival (OS) from mRCC diagnosis. The CM group showed a significant association with longer overall survival compared to the non-CM group in the PSM-unadjusted cohorts (p < 0.001, hazard ratio 0.49, 95% confidence interval 0.35-0.69), but no superiority was noted in the adjusted cohorts. The median DFS after CM was 24 months, with no significant differences based on relapse timing. Notably, the international metastatic RCC database consortium risk categories and metastatic burden were associated with DFS. This study supports the potential of CM in mRCC management during the TKI/ICI era, although limitations including sample size and selection bias need to be considered.

A Multicenter, Single-Arm, Prospective Trial to Evaluate Efficacy and Safety of Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Carboplatin (DD-MVACarbo) Chemotherapy for Cisplatin-Ineligible Patients with Advanced Urothelial Cancer: Study Protocol of the CARBUNCLE Trial.

Unresectable, metastatic, advanced urothelial carcinoma (aUC) is an aggressive disease and is treated with platinum-containing first-line chemotherapy, followed by immune checkpoint inhibitors and antibody-drug conjugates. Response to first-line chemotherapy is a vital priority in sequential treatment strategies because a better response to first-line chemotherapy is associated with a better response to subsequent therapies. Gemcitabine plus carboplatin chemotherapy is conventionally recommended for cisplatin-ineligible patients. This multicenter, single-arm prospective trial will investigate whether dose-dense methotrexate, vinblastine, doxorubicin, and carboplatin (DD-MVACarbo) chemotherapy is superior to gemcitabine plus carboplatin chemotherapy in terms of efficacy in platinum-naïve, cisplatin-ineligible patients with aUC. After screening and registration, a total of 46 patients will be treated with this novel chemotherapy regimen. The primary endpoint is the objective response rate. The secondary endpoints include disease control rate, patient-reported outcomes, and adverse events. No evidence of this novel intervention is available as of July 2024. The results are expected to change the standard of care and improve the management of patients with aUC.