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Introduction Primary or metastatic urethral tumors are extremely rare. However, treatment strategies differ between primary and metastatic tumors. Therefore, establishing an accurate diagnosis is critically needed for initiating timely and appropriate therapy. Case presentation We describe the case of a 79‐year‐old man with prostate cancer treated with radiotherapy and androgen deprivation therapy. He presented with macroscopic hematuria as a symptom of anterior urethral tumor at follow‐up. Endoscopic tumor resection was performed. Hematoxylin and eosin staining showed adenocarcinoma component. Immunohistochemical staining revealed presence of metastatic prostate cancer to the urethra. Conclusion Regarding urethral tumors diagnosis, urologists should consider the possibility of metastasis from prostate cancer and perform immunohistochemical examination for establishing accurate diagnosis. Furthermore, if androgen deprivation therapy fails to suppress symptoms, radiotherapy or urethrectomy might be considered.

The effects of the type of anesthesia (spinal (SA) vs. general (GA)) used for transurethral resection of bladder tumor (TURBT) on non-muscle invasive bladder cancer (NMIBC) recurrence and progression are controversial and our aim is to investigate their associations. We identified 300 NMIBC patients who underwent initial TURBT with SA or GA. Cox’s regression analysis was performed to examine the effects of anesthesia on tumor recurrence. Among 300 patients, 153 (51.0%) received GA and 147 (49.0%) SA. The 5-year recurrence-free survival (RFS) rate was 59.9% in the GA group, which was significantly lower than that in the SA group (74.4%, p = 0.029). GA (HR 1.57, p = 0.048), male sex (HR 2.72, p = 0.012), and tumor multiplicity (HR 1.96, p = 0.006) were independently associated with tumor recurrence. In a subgroup of 137 patients with high-risk NMIBC, the 5-year RFS rate was 50.3% in the GA group, which was significantly lower than that in the SA group (77.6%, p = 0.020), and GA remained an independent indicator of tumor recurrence (HR 2.35, p = 0.016). However, no significant differences were observed in the RFS rates of low- to intermediate-risk NMIBC patients between the GA and SA groups. The RFS rate was lower in NMIBC patients who received GA during TURBT than in those who received SA. Volatile anesthesia may increase tumor recurrence, particularly in high-risk NMIBC patients, which may be due to the inhibition of the immune response system during surgery.

The aim of this study was to evaluate the clinical significance of the on-treatment C-reactive protein (CRP) status during systemic treatment as the predictive marker for the response of subsequent nivolumab monotherapy in patients with refractory metastatic renal cell carcinoma (mRCC). A total of 73 mRCC patients treated with nivolumab were retrospectively reviewed. We evaluated the serum CRP levels before and after molecular-targeted treatments. Patients whose CRP did not exceed baseline value were defined as the CRP-control group and the others were defined as the CRP-progression group. The clinical impact of CRP-control on the efficacy of nivolumab was assessed. Twenty-four patients (33%) were categorized into the CRP-control group. The CRP-control group patients (median PFS not reached) had significantly longer PFS than the CRP-progression group (median PFS 11.9 months, 95% confidence interval, CI 4.1–19.8, p = 0.038). The CRP-control group had a tendency of longer OS from nivolumab initiation than the CRP-progression group (p = 0.071). By multivariate analysis, the on-treatment CRP-control was the independent predictive factor for PFS (hazard ratio HR 0.37, 95% CI 0.14–0.99, p = 0.047). The on-treatment CRP-control could be the predictive factor for the efficacy of nivolumab in refractory mRCC patients.

Background The current guideline lacks evidence for creating individualized surveillance strategies for upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). Objective To create a novel risk model and to simulate individualized surveillance duration that dynamically illustrates the changing risk relationship of UTUC-related death and non-UTUC death, considering the impact of cigarette smoking. Design, setting, and participants This multicenter cohort study comprised 714 pTa-T4N0M0 UTUC patients, with a median follow-up duration of 65 mo. There were 279 (39.1%) nonsmokers, 260 (36.4%) current smokers, and 175 (24.5%) ex-smokers. Intervention All patients underwent RNU. Outcome measurements and statistical analysis The risks of UTUC death and non-UTUC death over time were estimated using parametric models for time to failure with Weibull distributions. Age-specific, stage-specific, and smoking status-specific surveillance durations were simulated based upon Weibull estimates. Results and limitations The hazard rate (HR) of non-UTUC death gradually increased over time in all age groups regardless of the smoking status, whereas that of UTUC-related death decreased markedly according to the pathological T (pT) stage and was affected by the smoking status. Among current smokers, the baseline HR of UTUC-related death in pT3/4 was higher than that of pT ≤2 and remained high even 10 yr after RNU. Among heavy smokers, the HR of UTUC-related death in all pT stages was highest at baseline and remained high after RNU, compared with nonsmokers, current smokers, or ex-smokers. We simulated specific time points when the risk of non-UTUC death was greater than that of UTUC-related death. Among patients ≥80 yr of with pT3N0M0, the risk of non-UTUC death was greater than that of UTUC-related death 1 yr after RNU in nonsmokers, but 7 yr for heavy smokers. Conclusions Our result revealed that smokers bear a long-term risk burden of UTUC-related death more than the risk of non-UTUC death. For UTUC smokers, longer-term surveillance duration is recommended even in elderly stage. Patient summary In the present study, we evaluated the risk transition of upper tract urothelial carcinoma (UTUC)-related death and non-cancer-related death over time. We found that smoking weighed a huge impact upon UTUC-related death compared with death from other cause, and therefore, we created a more individualized surveillance duration model.

Background Prostate cancer harboring cyclin-dependent kinase 12 (CDK12) abnormalities is a hot topic due to its distinctive clinical features, such as sensitivity to immune checkpoint inhibitors. In the last few years, precision medicine using comprehensive genome sequencing has become familiar, and the era of precision oncology has arrived in the field of prostate cancer. This study aimed to present the demographic characteristics of patients with CDK12 alterations. Methods In 12 patients with detected CDK12 alterations in our hospital between 2015 and 2021, we evaluated their genomic features and clinical course. CDK12 allelic status was classified into three groups: monoallelic loss, potentially biallelic loss, and biallelic loss based on the genome analyses. Results Seven patients already had metastatic cancer at the time of diagnosis, and all 12 patients had Gleason grade ≥ 4. Most cases of biallelic loss or potentially biallelic loss were metastatic cancers at the initial staging, and all these cases were categorized into Gleason grade 5. Two of the 12 patients had BRCA2/RB1 co-loss, and the other two had whole genome duplication. Five patients had a long-term survival of > 6 years, but two patients died within 4 years of diagnosis. Conclusion This is the first Japanese prostate cancer case series with CDK12 alterations. CDK12-altered prostate cancer is a heterogeneous disease, and accumulating cases with detailed information leads to precision oncology.

Background The use of whole-genome sequencing in clinical practice has revealed variable genomic characteristics across cancer types, one of which is whole-genome doubling (WGD), which describes the duplication of a complete set of chromosomes. Yet it is relatively rare in prostate cancer and no such case has ever been reported in Japanese patients. Case presentation A 54-year-old patient with prostatic adenocarcinoma with bone and lymph node metastases was started on androgen-deprivation therapy. As the prostate cancer turned castration-resistant, multimodal therapies including taxane- and platinum-based chemotherapy, androgen-receptor antagonist inhibitors, radiotherapy and radium-233 were introduced. Good controls of serum prostate-specific antigen (PSA) level and bone metastases were achieved for more than 13 years since after the initial treatment. During the treatment, a metastatic lymph node biopsy was performed to confirm the tumor histology, and spinal decompression surgery were performed for spinal compression due to lumber vertebral metastases. The immunohistochemical analysis identified PSA and androgen receptor positive tumor cells in both metastatic lesions, while no variable cancer cells were detected in the prostate on second biopsy. Whole-genome sequencing was performed on the biopsied metastatic lymph node in search for another possible treatment and it revealed that the tumor had WGD and CDK12 mutation. The WGD-positive tumor cells contained large and polymorphic nucleus, presumably reflecting on the ploidy abnormality of the chromosomes. Conclusions This report is the first case of a Japanese patient presenting with WGD, who survived more than 13 years with multimodal chemotherapies and radiotherapies.

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle‐invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa‐4N0‐2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2‐4N0‐2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer‐specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non‐MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC., We conducted a multicenter cohort study describing the clinicopathological characteristics of muscle‐invasive bladder recurrence developed after surgical management of upper tract urothelial carcinoma.

INTRODUCTION AND OBJECTIVE:The mechanism of radiation cystitis (RC) remains unknown, however, angiogenesis induced by hypoxia might be associated with it because hyperbaric oxygen therapy is clinic...

INTRODUCTION AND OBJECTIVE:The incidence of elderly males with VUR increases with age, likely to be due to the higher number of men with bladder outlet obstruction. Therefore, intravesical BCG inst...

Objective The indications of neoadjuvant chemotherapy (NAC) for lymph node-positive upper tract urothelial carcinoma (UTUC) have not been investigated regarding improved survival outcomes. Our specific aim was to compare the clinical outcomes of clinically node-positive UTUC patients who were treated by NAC followed by radical nephroureterectomy (RNU) or upfront RNU followed by adjuvant chemotherapy (AC). Materials and methods Among 966 UTUC patients, we identified 89 with clinical nodal involvement who received either NAC before RNU nor AC after upfront RNU. Cox proportional hazard models were employed to evaluate the impact of chemotherapy modality on the oncological outcomes. Results Of the patient cohort, 36 (40.4%) received NAC followed by RNU, whereas 53 (59.6%) underwent RNU followed by AC. Multivariate analysis revealed that tumor size ≥3 cm, clinical T4, and gemcitabine and cisplatin regimen were independent risk factors for disease recurrence, whereas NAC followed by RNU was an independent factor for favorable RFS. Furthermore, regarding cancer-specific survival (CSS), NAC followed by RNU remained an independent factor for favorable CSS. According to Kaplan-Meier analysis, the 1-year and 2-year RFS were 67.9% and 47.0%, respectively, in the NAC+RNU group, which were significantly higher than those in the RNU+AC group (43.9% and 24.6%, respectively, P = 0.006). Moreover, the 1-year and 2-year CSS were 80.5% and 64.2%, respectively, in the NAC+RNU group, which were higher than those in the RNU+AC group (68.6% and 48.2%, respectively, P = 0.016). Conclusion For node-positive UTUC patients, NAC followed by RNU was more clinically beneficial than RNU followed by AC.

This study aimed to investigate the long-term oncologic outcomes of laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) for patients with clinical and pathologic T3N0M0 upper tract urothelial carcinoma (UTUC). Among 375 UTUC patients who underwent radical nephroureterectomy, this study identified 144 pT3N0M0 patients as cohort 1 after propensity score (PS) matching. Among 399 UTUC patients, the study identified 110 cT3N0M0 patients as cohort 2 after PS matching. Oncologic outcomes such as intravesical recurrence-free survival (IVRFS) and cancer-specific survival (CSS) were assessed by multivariate Cox’s regression analysis. Cohort 1 of pT3N0M0 UTUC had 3-year CSS and IVRFS rates of 67.9 and 52.7%, respectively, in the LRNU group, which were significantly lower than in the ORNU group (81.4%, p = 0.039 and 71.6%, p = 0.046). The multivariate Cox’s regression analysis identified the type of surgical approach (LRNU vs. ORNU) as one of the independent prognostic factors for CSS (hazard rate [HR], 1.88, p = 0.043) and IVRFS (HR, 1.75, p = 0.049). Cohort 2 of cT3N0M0 UTUC had 3-year CSS and IVRFS rates of 48.5 and 41.4%, respectively, in the LRNU group, which were significantly lower than in the ORNU group (65.8%, p = 0.049 and 67.2%, p = 0.047), and the type of surgical approach (LRNU vs. ORNU) remained as one of the independent prognostic factors for CSS and IVRFS. Based on clinical and pathologic T3N0M0 UTUC populations after PS adjustments, LRNU resulted in poorer CSS and IVRFS than ORNU.