Prognostic impact of histological discordance between transurethral resection and radical cystectomy.

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.

Associations between early changes in the neutrophil-to-lymphocyte ratio after radical nephroureterectomy and treatment outcomes.

OBJECTIVES: This study explored the impacts of peri-operative changes in the neutrophil-to-lymphocyte ratio (NLR) on the survival rate after radical nephroureterectomy. METHODS: This retrospective analysis included a multicentric cohort of patients diagnosed with upper tract urothelial carcinoma (UTUC) who had undergone radical nephroureterectomy from 2012 to 2021. We assessed the preoperative NLR, postoperative NLR, delta-NLR (difference between postoperative and preoperative NLRs), and NLR change (ratio of postoperative to preoperative NLR). Additionally, patients were categorized according to increases in their preoperative and/or postoperative NLRs. Associations of survival with peri-operative changes in the NLR were investigated using Cox multivariate regression models. RESULTS: A total of 488 patients were included in the study, with a median age of 73 years. Among the patients, 105 (21.5%) exhibited elevated preoperative and postoperative NLRs, 88 (18.0%) exhibited elevated preoperative NLR only, 53 (10.9%) exhibited elevated postoperative NLR only, and 242 (49.6%) exhibited normal NLRs. Multivariate analysis indicated significant negative correlations between both preoperative and postoperative increased NLRs and oncological outcomes, including nonurothelial tract recurrence-free survival and cancer-specific survival (hazard ratio [HR]: 1.65, P = 0.017; HR: 2.12, P = 0.014, respectively). CONCLUSION: This is the first study to evaluate the association between peri-operative changes in the NLR and the outcomes of patients with UTUC who underwent radical nephroureterectomy. Patients with elevated NLRs at both time points experienced considerably worse outcomes. Further research should explore whether increases in the NLR during long-term follow-up could indicate impending disease recurrence.

Survival outcome of chemotherapy-naïve castration-resistant prostate cancer treated with new-generation androgen receptor axis-targeted agents in real-world analysis.

PURPOSE: The androgen receptor axis-targeted (ARAT) agents abiraterone and enzalutamide have been introduced against castration-resistant prostate cancer (CRPC). However, determining which of these agents should be used first is a clinical challenge. Therefore, in this study, we compared the efficacy of first-line abiraterone and enzalutamide treatments in chemotherapy-naïve patients with CRPC. METHODS: A total of 242 chemotherapy-naïve CRPC cases treated with first-line ARAT were analyzed. Outcome measures were PSA response, PSA progression-free survival (PSA-PFS), time to treatment failure (TTF), cancer specific survival (CSS), and overall survival (OS). RESULTS: Abiraterone (A) and enzalutamide (E) were administered to 61 and 181 patients, respectively. The median PSA response rate (- 65.4% [A] and - 78.8% [E], p = 0.0341), PSA decline ≥ 30% (55.7% [A] and 72.9% [E], p = 0.0183), PSA-PFS (median 4 months [A] and 8 months [E], p = 0.0126), TTF (median 6 months [A] and 14 months [E], p < 0.0001), CSS (median 45 months [A] and not reached [E], p < 0.0001), and OS (median 28 months [A] and 80 months [E], p < 0.001) were significantly better in the enzalutamide group. In the multivariate analyses for CSS and OS, ALP (p = 0.00376) and ARAT (p < 0.001) (CSS), evidence of metastasis (p = 0.0467), Hb (p = 0.00205), and ARAT (p = 0.00514) (OS) were significant factors, respectively. CONCLUSION: This study showed that PSA response, PSA-PFS, TTF, CSS, and OS were better with first-line enzalutamide administration. Direct inhibition of androgen receptor signaling by enzalutamide is associated with better clinical outcomes.

Clinical characteristics of secondary bladder cancer developing after low-/high-dose-rate brachytherapy to treat localized prostate cancer.

BACKGROUND: To explore correlations between the clinical attributes of secondary bladder cancer and brachytherapy, we retrospectively reviewed our institutional database on patients with localized prostate cancer who underwent low-dose-rate brachytherapy (LDR-BT) or high-dose-rate brachytherapy (HDR-BT) with or without external beam radiation therapy (EBRT) or radical prostatectomy (RP). METHODS: From October 2003 to December 2014, 2551 patients with localized prostate cancer were treated at our institution. Of these, data on 2163 were available (LDR-BT alone: n = 953; LDR-TB with EBRT: n = 181; HDR-BT with EBRT: n = 283; RP without EBRT: n = 746). The times of secondary bladder cancer development subsequent to radical treatment, and their clinical characteristics, were studied. RESULTS: Age-adjusted Cox's regression analyses indicated that brachytherapy did not significantly impact the incidence of secondary bladder cancer. However, the pathological characteristics of such cancer differed between patients treated via brachytherapy and RP without EBRT; invasive bladder cancer was more common in such patients. CONCLUSION: The risk for secondary bladder cancer was not significantly increased after brachytherapy compared to non-irradiation therapy. However, brachytherapy patients exhibited a higher incidence of invasive bladder cancer. Therefore, meticulous follow-up is crucial for early detection and treatment of bladder cancer in such patients.

How long is long enough to secure disease control after low-dose-rate brachytherapy in combination with other modalities in intermediate-risk, localized prostate cancer?

PURPOSE: Previous studies have demonstrated excellent overall outcomes in patients who underwent low-dose-rate brachytherapy (LDR-BT) in intermediate-risk, localized prostate cancer (PCa). We thus investigated the appropriate length of time before completing prostate-specific antigen (PSA) monitoring after treatment. PATIENTS AND METHODS: Between 2003 and 2014, 710 localized, intermediate-risk PCa patients underwent LDR-BT with or without supplemental external beam radiotherapy (EBRT). Data from 567 of those patients was analyzed in this study. Neoadjuvant hormonal therapy (NHT) was administered to 315 patients (55.6 %) and NHT with adjuvant hormonal therapy (AHT) to 59 patients (10.4 %), as per the protocol of a prospective randomized controlled trial (SHIP0804). We stratified patients by posttreatment PSA levels at specific times and assessed the factors for association with biochemical recurrence (BCR) and for clinical progression (CP). RESULTS: The median follow-up was 109 months (range, 60-205 months). Of 529 patients who were BCR-free at 3 years after treatment, 56 subsequently developed BCR, and 47 developed CP. PSA at 3 and 5 years after treatment were significantly correlated with long-term oncological outcomes. No patients with 5-year PSA levels ≤0.1 ng/mL subsequently developed BCR or CP. CONCLUSION: Discontinuation of PSA monitoring could be discussed with patients with intermediate-risk PCa as a reasonable option if PSA levels remain ≤0.1 ng/mL at 5 years after LDR-BT, either alone or with other combined modalities, as subsequent recurrences are quite rare.

[The Effect of Local Therapy on Brain Metastasis of Renal Cell Carcinoma].

We compared brain metastasis of renal cell carcinoma (RCC) in patients who received tyrosine kinase inhibitors (TKIs) ; 17 received local therapy, while 16 did not. The median survival rate was 19 months in the local therapy group and 11 months in the tyrosine kinase inhibitor alone group, showing no significant difference (p＝0.52). Symptoms such as paralysis, headache, and dysarthria occurred due to brain metastasis. These symptoms improved in 8 out of 10 patients in the local therapy group. There were no cases of grade 3 or higher complications due to local therapy. Although local therapy did not prolong the overall survival, an improvement in symptoms was observed, suggesting that it is acceptable as palliative treatment.

Urethral catheter entrapped in vesicourethral anastomotic sutures after laparoscopic radical prostatectomy successfully removed by transurethral approach.

Introduction: Urethral catheter entrapped in vesicourethral anastomotic sutures after radical prostatectomy is a relatively common complication. We herein present a novel and safe technique to remove urethral catheter. Case presentation: A 64-year-old man was diagnosed with prostate cancer. Subsequently he underwent laparoscopic radical prostatectomy. On postoperative Day 7, the patient experienced difficulty in removing the catheter, and entanglement of the suture with the urinary catheter was suspected. After conservative follow-up, a rigid endoscope was inserted into the urethra beside urethral catheter, identifying suture entanglement with the catheter. Finally, the suture was cut with scissor forceps. Conclusion: To the best of our knowledge, this is the first reported case in which scissor forceps were used to cut the entangled thread in such a complication. This case highlights a novel but simple method for difficult removal of an entrapped catheter.

Docetaxel versus androgen receptor signaling inhibitor (ARSI) against chemo-naïve castration-resistant prostate cancer (CRPC): propensity score matched analysis in real world.

PURPOSE: Although docetaxel and ARSI are picked up as treatment options against chemo-naïve metastatic CRPC in clinical guidelines for prostate cancer, there is no clear evidence which agent should be introduced as first line treatment. Therefore, we investigated our CRPC cohort treated with docetaxel or ARSI as first-line agent against chemo-naïve CRPC to solve these clinical questions. PATIENTS AND METHODS: A total of 345 chemotherapy-naïve CRPC patients introduced to first-line docetaxel or ARSI (abiraterone or enzalutamide) between March 2006 and April 2017 at Jikei University Hospital and its affiliated institutions were included in this study. Propensity score matching method was used to minimize the patients' background. The outcome measures were PSA response rate, PSA decline ≥ 90%, cancer specific survival (CSS) and overall survival (OS). RESULTS: PSA decline correlated OS and CSS (p = 0.027, < 0.001, respectively) and median PSA decline rate was 60.4% in docetaxel group and 85.7% in ARSI group (p = 0.0311). Median OS was 33 m (95%CI: 27-53) in docetaxel group and 61 m (95%CI: 47-NA) in ARSI group (p = 0.0246). Median CSS was 34 m (95%CI: 27-53) in docetaxel group and NR (not reached) (95%CI: 61-NA) in ARSI group (p = 0.000133) in propensity score matching cohort. In multivariate analysis, ARSI induction first showed significantly better for OS and CSS (p = 0.0033 and < 0.001, respectively). CONCLUSION: In this study, better survival outcome with ARSI induction first than docetaxel against chemo-naïve CRPC. And the candidates who had survival benefit by induction docetaxel first could not be found in this study.

Site-Specific Differences of Eligibility for Adjuvant Immunotherapy Among Urothelial Carcinoma Patients Treated With Radical Surgery: Results From a Multicenter Cohort Study.

BACKGROUND: The CheckMate274 trial has reported enhanced disease-free survival rates in patients with stage pT3-4/ypT2-4 or pN+ urothelial carcinoma (UC) undergoing adjuvant nivolumab therapy. This study compares prognostic differences between urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analyzed data from 719 patients with UC who underwent radical surgery, stratifying to patients at stage pT3-4 and/or pN+ without neoadjuvant chemotherapy (NAC) or at ypT2-4 and/or ypN+ with NAC (potential candidates for adjuvant immunotherapy), and to those who were not candidates for adjuvant immunotherapy. We used Kaplan-Meier curves to assess oncological outcomes, particularly nonurothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Risk factors were identified by Cox regression analysis. RESULTS: Kaplan-Meier curves showed significantly lower NUTRFS, CSS, and OS for potential adjuvant immunotherapy candidates than for noncandidates in each UCB and UTUC group. NUTRFS, CSS, and OS did not differ significantly between adjuvant immunotherapy candidates with UBC or UTUC. Trends were similar among patients ineligible for adjuvant immunotherapy. Pathological T stage (pT3-4 or ypT2-4), pathological N stage, and lymphovascular invasion (LVI) were independent predictors of oncological outcomes on multivariate analysis. CONCLUSION: The criteria for adjuvant immunotherapy candidates from the CheckMate 274 trial can also effectively stratify UC patients after radical surgery. Substantial clinical significance is attached to LVI status as well as to pathological T and N status, suggesting that LVI status should be considered when selecting suitable candidates for adjuvant immunotherapy.

The Impact of ABO Blood Type on Developing Venous Thromboembolism in Cancer Patients: Systematic Review and Meta-Analysis.

The impact of ABO blood type in the development of venous thromboembolism in cancer patients remains controversial. To develop a sense of the current opinion in this area, we conducted a systematic review and meta-analysis. In March 2021, we performed a systematic search of PubMed, the Cochrane library, and Scopus for studies that compared cancer patients who had a blood type of either O or non-O (A, B, and AB). Our objective was to use multivariate logistic regression analysis to determine how ABO blood type was associated with the development of venous thromboembolism. Our selection criteria were met by a total of nine studies in 25,884 patients for the systematic review and five studies in 22,777 patients for the meta-analysis. In cancer patients, we found that non-O blood type was associated with a nearly two-fold increase in risk of venous thromboembolism (pooled OR: 1.74, 95% CI: 1.44-2.10). Additionally, among the eligible patients, 21,889 patients were post-operative urological cancer patients. In these patients, the analysis also showed an association between non-O blood type and increasing risk of venous thromboembolism after pelvic surgery for malignancy (pooled OR: 1.73, 95% CI: 1.36-2.20). Our meta-analysis suggested that non-O blood type is a risk factor for venous thromboembolism among patients with cancer. As blood type is routinely determined preoperatively by objective and standardized methods, we anticipate that our results will be useful for managing venous thromboembolism in cancer patients, especially after pelvic surgery for urological cancers.

Clear identification of the rare solitary external iliac lymph node metastasis of testicular cancer by using indocyanine green fluorescence guidance.

INTRODUCTION: There are few reports on indocyanine green fluorescence-guided surgery in testis-related diseases. CASE PRESENTATION: A 38-year-old man underwent orchiectomy for left testicular cancer. Pathological diagnosis was pT1 seminoma. Seven years after the surgery, solitary left external iliac lymph node metastasis was suspected. We decided to perform laparoscopic lymph node dissection combined with indocyanine green fluorescence injection. During the operation, we injected indocyanine green fluorescence into his left inner inguinal ring and found that the lymph node was directly drained from the injection point. The pathological diagnosis of the indocyanine green fluorescence-positive left external iliac lymph node was testicular cancer metastasis. CONCLUSION: We experienced a case of solitary left external iliac lymph node recurrence in testicular cancer. Using indocyanine green fluorescence injection, we could visualize the lymphatic drainage route, which helped us identify the lymph node as the primary landing site of metastasis.

Performance of Indocyanine Green Fluorescence for Detecting Lymph Node Metastasis in Prostate Cancer: A Systematic Review and Meta-analysis.

PURPOSE: The use of sentinel lymph node dissection in several cancers has been gaining attention with the emergence of indocyanine green fluorescence. We performed a meta-analysis to assess the diagnostic performance of indocyanine green fluorescence in detecting lymph node metastasis in prostate cancer patients. METHODS: A literature search was conducted using PubMed, Cochrane Library, and SCOPUS on November 30, 2020, to identify eligible studies. Studies were eligible if they investigated the diagnostic performance of indocyanine green fluorescence before pelvic lymph node dissection in prostate cancer patients and reported the number of true positives, false positives, false negatives, and true negatives on lymph node-based analysis in comparison to histopathologic findings in the dissected specimen. RESULTS: Our systematic review covered 11 studies published between 2011 and 2020, with 519 patients, and our meta-analysis included 9 studies with 479 patients. Based on lymph node analysis of indocyanine green fluorescence, the results showed pooled sensitivity and specificity at 0.75 (95% confidence interval [CI] 0.49 to 0.90) and 0.66 (95% CI 0.61 to 0.70), respectively. The diagnostic odds ratio was 6.0 (95%CI 2 to 21). Several lymphatic drainage routes also showed sentinel lymph nodes localized outside the ordinal pelvic lymph node template. CONCLUSIONS: We noted relatively low diagnostic performance for lymph node metastasis, suggesting that indocyanine fluorescence may not currently be a viable alternative to pelvic lymph node dissection in prostate cancer patients. However, this technique shows novel lymphatic drainage routes and underscores the importance of lymph nodes not removed in ordinary dissection.

Everolimus-induced gastric antral vascular ectasia in advanced renal cancer.

INTRODUCTION: Although several medical, endoscopic, and surgical treatment options are available, the management of gastric antral vascular ectasia remains clinically challenging. We report a case of gastric antral vascular ectasia due to everolimus use in a patient with advanced renal cancer. CASE PRESENTATION: A 71-year-old man was diagnosed with right-sided renal cancer and multiple lung metastases. In the period of everolimus as third-line therapy, endoscopy of the upper gastrointestinal tract revealed everolimus-induced gastric antral vascular ectasia. Endoscopic argon plasma coagulation and variceal ligation were repeated seven times within a month of everolimus cessation. Subsequently, an antrectomy was performed; his postoperative course was uneventful. CONCLUSION: Based on our experience, we believe that an antrectomy is important in the management of mammalian target of rapamycin inhibitor-related gastric antral vascular ectasia.