Real-world sequential treatment patterns and clinical outcomes among patients with advanced urothelial carcinoma in Japan.

OBJECTIVES: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. METHODS: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. RESULTS: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. CONCLUSIONS: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.

[Advanced Bladder Cancer with Multiple Pulmonary Metastases Treated with Paclitaxel/Ifosfamide/Nedaplatin Therapy : Two Case Reports].

The standard treatment for advanced urothelial carcinoma includes platinum-based chemotherapy and programmed cell death protein 1 or programmed death ligand 1 inhibitors. However, urothelial carcinomas are often associated with both intrinsic and acquired resistance to these treatments. Paclitaxel, ifosfamide, and nedaplatin (TIN) chemotherapy has been proven to be effective as the second- or third-line treatment for platinum-resistant advanced urothelial cancer. Herein, we report two cases of patients with advanced bladder cancer resistant to platinum-based chemotherapy or pembrolizumab, who were treated with TIN chemotherapy. The first case was in a 66-year-old woman treated with gemcitabine and cisplatin (GC) chemotherapy followed by gemcitabine, paclitaxel, and cisplatin chemotherapy for multiple pulmonary metastases after radical cystectomy. Following reduction in pulmonary metastases after six courses of TIN treatment, metastasectomy and two courses of adjuvant TIN treatment were administered, with no recurrence for eight years. The other case was in a 70-year-old man treated with GC chemotherapy and pembrolizumab for invasive bladder cancer and multiple pulmonary metastases. We treated this patient with salvage pelvic exenteration. Pulmonary metastases significantly decreased after six courses of TIN chemotherapy. After a partial response for seven months; the patient died due to a novel cerebellar metastasis after six courses of TIN chemotherapy. Thus, we conclude that TIN chemotherapy can be considered as a third line treatment for advanced urothelial cancer resistant to platinum-based chemotherapy and pembrolizumab.

Immune-related adverse events in urothelial cancer patients: Adjustment for immortal time bias.

To investigate the association between the onset, severity, and type of immune-related adverse events (irAEs) and the efficacy of pembrolizumab in patients with platinum-pretreated advanced urothelial carcinoma (UC), we retrospectively collected clinical datasets of 755 patients and conducted landmark analysis. Patients who survived for fewer than 3 months were excluded from the evaluation to reduce the immortal time bias. In total, 620 patients were evaluated, of whom 220 patients (35.5%) experienced grade ≥2 irAEs, including 134 patients with grade 2 irAEs and 86 with grade ≥3 irAEs. Propensity score matching extracted 198 patients with and without grade ≥2 irAEs. The onset of grade ≥2 irAEs was associated with longer median progression-free survival (PFS) (8.3 months vs. 4.5 months, p = 0.003) and overall survival (OS) (20.4 months vs. 14.3 months, p = 0.031) and a higher objective response rate (ORR) (44.8% vs. 30.2%, p = 0.004). Patients with grade 2 irAEs had significantly better oncological outcomes (PFS, OS, and ORR) than grade ≤1 and ≥3 irAEs. Patients with grade ≥3 irAEs had worse outcomes than grade 2 irAEs. Endocrine and skin irAEs were related with better survival outcomes, and the rate of severities was lower in these categories. In conclusion, the occurrence of irAEs, particularly low-grade irAEs, was predictive of pembrolizumab efficacy in patients with platinum-pretreated advanced UC.

Baseline factors and surgical procedures affecting changes in lower urinary tract symptoms after robot-assisted radical prostatectomy: the impact of nerve-sparing.

PURPOSE: To determine baseline factors and surgical procedures associated with clinically meaningful improvement or deterioration of lower urinary tract symptoms (LUTS) after robot-assisted radical prostatectomy (RARP). METHODS: We retrospectively reviewed our RARP database and analyzed the changes in the International Prostate Symptom Score (IPSS) at baseline and 1, 3, 6, and 12 months postoperatively. Multivariable ordinal logistic regression analysis was performed to determine variables that predicted clinically meaningful improvement (∆IPSS ≤ -5) or deterioration (∆IPSS ≥ 5) in LUTS after RARP. RESULTS: A total of 172 patients were eligible for analysis. Patients aged ≥ 70 reported a higher IPSS before and after RARP (all p < 0.05). Patients with a prostate volume of > 30 mL or body mass index of < 24 kg/m2 had worse preoperative LUTS; however, the difference disappeared after RARP. While patients with or without nerve-sparing (NS) had a similar preoperative LUTS burden, the NS group reported significantly lower IPSS than the non-NS group at all postoperative time points (p < 0.05). Twelve months after RARP, LUTS improved in 27% and worsened in 6% of patients in the NS group, compared with 20% and 24% of those in the non-NS group, respectively (p = 0.018). Preoperative IPSS (OR, 0.84; 95% CI, 0.79-0.89) and NS (OR, 0.39; 95% CI, 0.18-0.83) were independently associated with clinically meaningful changes of LUTS at 12 months after RARP. CONCLUSION: Other than baseline LUTS severity, NS was the only independent factor associated with clinically meaningful changes in LUTS after RARP.

Associations Among Hypersensitivity, Vagal Tone, and Mood State in Adults.

Although many previous studies have reported the relationship between hypersensitivity and vagal function in children, the relationship in adults is unclear. This study investigates the relationship between hypersensitivity and vagal function, discomfort to sensory stimuli, and daily mood states in healthy adults. Using a questionnaire, 39 healthy adults were divided into hypersensitivity and control groups. We compared the baseline respiratory sinus arrhythmia (RSA), reflecting vagal tone and reactivity, subjective discomfort to sensory stimuli, and daily mood status between groups. Those in the hypersensitivity group had significantly lower baseline RSA and were more likely to experience greater RSA variability and discomfort during exposure to sensory stimuli than the control group. We found no significant difference between groups in daily mood status. These findings suggest that vagal function is an important marker of hypersensitivity in healthy adults.

Relationships Among Hypersensitivity, Parasympathetic Function, and Mood States in AdultsPrevious studies in children have reported many associations between sensory characteristics, such as hypersensitivity to sensory stimuli, and parasympathetic function, but the association in adults is not clear. This study divided 39 healthy adults into a hypersensitivity group and a control group and compared their parasympathetic function, discomfort to sensory stimuli, and daily mood. We found that the hypersensitivity group had significantly lower baseline parasympathetic function and tended to experience greater fluctuations in parasympathetic activity and discomfort during sensory stimulation than the control group. However, we found no significant difference in daily mood between the groups. This suggests that parasympathetic function is an important marker of hypersensitivity in healthy adults. This may help therapists support those with hypersensitivity. Future research is needed in clinical practice.

Capture of emotional responses under a simulated earthquake experience using near-infrared spectroscopy and virtual reality.

AIM: In a previous study, we reported that watching two-dimensional videos of earthquakes significantly reduced sympathetic nerve activity in healthy young adults. In the present study, we aimed to investigate the emotional responses to earthquakes using immersive virtual reality (VR), which can provide a more realistic experience. METHODS: In total, 24 healthy young adults (12 males, 21.4 ± 0.2 years old) participated. Participants were required to watch earthquake and neutral videos while wearing a head-mounted display and near-infrared spectroscopy (NIRS), during which physiological signals, including pulse rate and cerebral blood flow (CBF) in the dorsolateral prefrontal cortex, were measured. We also analyzed changes in sympathetic and parasympathetic indices and obtained seven emotion ratings: valence, arousal, dominance, fear, astonishment, anxiety, and panic. RESULTS: The VR earthquake videos evoked negative subjective emotions, and the pulse rate significantly decreased. Sympathetic nerve activity tended to decrease, whereas CBF in the left prefrontal cortex showed a slight increase, although this was not significant. CONCLUSIONS: This study showed that measurements combined with NIRS and immersive VR have the potential to capture emotional responses to different stimuli.

Preoperative ipilimumab/nivolumab combination therapy reduced operation risk by downstaging the inferior vena cava tumor thrombus extending to the right atrium in a metastatic renal cell carcinoma: A case report.

The success of immune checkpoint inhibitors in metastatic renal cell carcinoma (RCC) has renewed interest in studying these agents in preoperative settings. Here, we present a case of metastatic RCC with an inferior vena cava (IVC) tumor thrombus extending to the right atrium. Preoperative systemic therapy with ipilimumab/nivolumab was initiated for four cycles. The IVC tumor thrombus level was significantly downstaged from IV to I according to the Mayo classification, which enabled us to perform cytoreductive nephrectomy and IVC thrombectomy without extracorporeal circulation. Preoperative ipilimumab/nivolumab may lead to significant downstaging of caval tumor thrombus in metastatic RCC.