Comparison of perioperative outcomes and complications between intracorporeal, extracorporeal, and hybrid ileal conduit urinary diversion during robot-assisted radical cystectomy: a comparative propensity score-matched analysis from nationwide multi-institutional study in Japan.

BACKGROUND: To investigate the impact of different urinary diversion (UD) techniques on the peri- and postoperative complications of robot-assisted radical cystectomy (RARC) with ileal conduit. METHODS: We retrospectively analyzed 373 patients undergoing RARC with ileal conduit at 11 institutions in Japan between April 2018 and December 2021. Propensity score weighting was performed to adjust for confounding factors such as age, sex, body mass index, performance status, American Society of Anesthesiologists score, previous abdominal surgery, neoadjuvant chemotherapy, and preoperative high T stage (≥ cT3) and high N stage (≥ cN1). Perioperative complications were then compared among three groups: extracorporeal, intracorporeal, and hybrid urinary diversion (ECUD, ICUD, and HUD, respectively). RESULTS: A total of 150, 68, and 155 patients received ECUD, HUD, and ICUD, respectively. Bowel reconstruction time and UD time were significantly shorter in the ECUD group (p < 0.001), and console time was significantly longer and blood loss was significantly higher in the ICUD group (p < 0.001). For postoperative complications (Clavien-Dindo Classification grade ≥ 3), surgical site infection (p = 0.004), pelvic abscess (p = 0.013), anastomotic urine leak (p = 0.007), and pelvic organ prolapse (p = 0.011) significantly occurred in the ECUD group. For all grades, ileus was more common in the HUD group, whereas anastomotic stricture was more common in the ECUD group compared with the other groups (p < 0.05). CONCLUSIONS: Severe complications did not increase after HUD and ICUD compared with ECUD; however, console time tended to be longer and blood loss was slightly higher during RARC.

Unveiling the Genomic Landscape of Intraductal Carcinoma of the Prostate Using Spatial Gene Expression Analysis.

Intraductal carcinoma of the prostate (IDCP) has recently attracted increasing interest owing to its unfavorable prognoses. To effectively identify the IDCP-specific gene expression profile, we took a novel approach of characterizing a typical IDCP case using spatial gene expression analysis. A formalin-fixed, paraffin-embedded sample was subjected to Visium CytAssist Spatial Gene Expression analysis. IDCP within invasive prostate cancer sites was recognized as a distinct cluster separate from other invasive cancer clusters. Highly expressed genes defining the IDCP cluster, such as MUC6, MYO16, NPY, and KLK12, reflected the aggressive nature of high-grade prostate cancer. IDCP sites also showed increased hypoxia markers HIF1A, BNIP3L, PDK1, and POGLUT1; decreased fibroblast markers COL1A2, DCN, and LUM; and decreased immune cell markers CCR5 and FCGR3A. Overall, these findings indicate that the hypoxic tumor microenvironment and reduced recruitment of fibroblasts and immune cells, which reflect morphological features of IDCP, may influence the aggressiveness of high-grade prostate cancer.

Radical prostatectomy trends between 2010 and 2020 in Ehime, Japan, identified using data from the Medical Investigation Cancer Network (MICAN) study.

OBJECTIVES: The use of radical prostatectomy is increasing with the rising incidence of prostate cancer. We assessed the surgical trends related to radical prostatectomy using data from a multi-center, retrospective cohort study, the MICAN (Medical Investigation Cancer Network) study, which was conducted in all the urology-related medical facilities in Ehime Prefecture, Japan. METHODS: We compared data from the MICAN study with prostate biopsy registry data collected in Ehime between 2010 and 2020 and recorded the surgical trends. RESULTS: There was a significant increase in the mean age of patients with positive biopsies, and the positivity rate increased from 46.3% in 2010 to 60.5% in 2020, while the number of biopsies obtained decreased. The number of radical prostatectomies performed increased over the years, with robot-assisted radical prostatectomy becoming the predominant procedure. In 2020, robot-assisted radical prostatectomies accounted for 96.0% of the surgeries performed. The age at surgery also gradually increased. Of the registered patients aged ≤75 years, 40.5% underwent surgery in 2010, compared with 83.1% in 2020. The prevalence of surgery also increased from 4.6% to 29.8% in patients aged >75 years. There was a gradual increase in the proportion of high-risk cases, from 29.3% to 44.0%, but a decrease in that of low-risk cases, from 23.8% in 2010 to 11.4% in 2020. CONCLUSIONS: We have shown that the number of radical prostatectomies performed in Ehime is increasing in patients aged both ≤75 and >75 years. The proportion of low-risk cases has decreased, while that of high-risk cases has increased.

Spatial Gene Expression Analysis Reveals Characteristic Gene Expression Patterns of De Novo Neuroendocrine Prostate Cancer Coexisting with Androgen Receptor Pathway Prostate Cancer.

Neuroendocrine prostate carcinoma (NEPC) accounts for less than 1% of prostate neoplasms and has extremely poorer prognosis than the typical androgen receptor pathway-positive adenocarcinoma of the prostate (ARPC). However, very few cases in which de novo NEPC and APRC are diagnosed simultaneously in the same tissue have been reported. We report herein a 78-year-old man of de novo metastatic NEPC coexisting with ARPC treated at Ehime University Hospital. Visium CytAssist Spatial Gene Expression analysis (10× genetics) was performed using formalin-fixed, paraffin-embedded (FFPE) samples. The neuroendocrine signatures were upregulated in NEPC sites, and androgen receptor signatures were upregulated in ARPC sites. TP53, RB1, or PTEN and upregulation of the homologous recombination repair genes at NEPC sites were not downregulated. Urothelial carcinoma markers were not elevated. Meanwhile, Rbfox3 and SFRTM2 levels were downregulated while the levels of the fibrosis markers HGF, HMOX1, ELN, and GREM1 were upregulated in the tumor microenvironment of NEPC. In conclusion, the findings of spatial gene expression analysis in a patient with coexisting ARPC and de novo NEPC are reported. The accumulation of cases and basic data will help with the development of novel treatments for NEPC and improve the prognosis of patients with castration-resistant prostate cancer.

Association between previous negative biopsies and lower rates of progression during active surveillance for prostate cancer.

PURPOSE: To test any-cause discontinuation and ISUP GG upgrading rates during Active Surveillance (AS) in patients that underwent previous negative biopsies (PNBs) before prostate cancer (PCa) diagnosis vs. biopsy naive patients. METHODS: Retrospective analysis of 961 AS patients (2008-2020). Three definitions of PNBs were used: (1) PNBs status (biopsy naïve vs. PNBs); (2) number of PNBs (0 vs. 1 vs. ≥ 2); (3) histology at last PNB (no vs. negative vs. HGPIN/ASAP). Kaplan-Meier plots and multivariable Cox models tested any-cause and ISUP GG upgrading discontinuation rates. RESULTS: Overall, 760 (79.1%) vs. 201 (20.9%) patients were biopsy naïve vs. PNBs. Specifically, 760 (79.1%) vs. 138 (14.4%) vs. 63 (6.5%) patients had 0 vs. 1 vs. ≥ 2 PNBs. Last, 760 (79.1%) vs. 134 (13.9%) vs. 67 (7%) patients had no vs. negative PNB vs. HGPIN/ASAP. PNBs were not associated with any-cause discontinuation rates. Conversely, PNBs were associated with lower rates of ISUP GG upgrading: (1) PNBs vs. biopsy naïve (HR:0.6, p = 0.04); (2) 1 vs. 0 PNBs (HR:0.6, p = 0.1) and 2 vs. 0 PNBs, (HR:0.5, p = 0.1); (3) negative PNB vs. biopsy naïve (HR:0.7, p = 0.3) and HGPIN/ASAP vs. biopsy naïve (HR:0.4, p = 0.04). However, last PNB ≤ 18 months (HR:0.4, p = 0.02), but not last PNB > 18 months (HR:0.8, p = 0.5) were associated with lower rates of ISUP GG upgrading. CONCLUSION: PNBs status is associated with lower rates of ISUP GG upgrading during AS for PCa. The number of PNBs and time from last PNB to PCa diagnosis (≤ 18 months) appear also to be critical for patient selection.

Active surveillance for prostate cancer: comparison between incidental tumors vs. tumors diagnosed at prostate biopsies.

PURPOSE: To test discontinuation rates during Active Surveillance (AS) in patients diagnosed with incidental prostate cancers (IPCa) vs. tumors diagnosed at prostate biopsies (BxPCa). METHODS: Retrospective single center analysis of 961 vs. 121 BxPCa vs. IPCa patients (2008-2020). Kaplan-Meier plots and multivariable Cox regression models tested four different outcomes: (1) any-cause discontinuation; (2) discontinuation due to ISUP GG upgrading; (3) biopsy discontinuation due to ISUP GG upgrading or > 3 positive cores; (4) biopsy discontinuation or suspicious extraprostatic extension at surveillance mpMRI. Then, multivariable logistic regression models tested rates of clinically significant PCa (csPCa) (ISUP GG ≥ 3 or pT ≥ 3a or pN1) after radical prostatectomy (RP). RESULTS: Median time follow-up was 35 (19-64) months. IPCa patients were at lower risk of any-cause (3-year survival: 79.3 vs. 66%; HR: 0.5, p = 0.001) and biopsy/MRI AS discontinuation (3-year survival: 82.3 vs. 72.7%; HR: 0.5, p = 0.001), compared to BxPCa patients. Conversely, IPCa patients exhibited same rates of biopsy discontinuation and ISUP GG upgrading over time, relative to BxPCa. In multivariable logistic regression models, IPCa patients were associated with higher rates of csPCa at RP (OR: 1.4, p = 0.03), relative to their BxPCa counterparts. CONCLUSION: AS represents a safe management strategy for IPCa. Compared to BxPCa, IPCa patients are less prone to experience any-cause and biopsy/MRI AS discontinuation. However, the two mentioned groups present similar rates of biopsy discontinuation and ISUP GG upgrading over time. In consequence, tailored AS protocols with scheduled repeated surveillance biopsies should be offered to all newly diagnosed IPCa patients.

Summary of the Clinical Practice Guidelines for Penile Cancer 2021 by the Japanese Urological Association.

Penile cancer is a rare cancer for which no medical guidelines have been established before in Japan. These guidelines aim to standardize, as much as possible, the therapeutic modality for penile cancer, for which empirical evidence is limited on a global scale, thereby bolstering therapeutic outcomes for patients with penile cancer. The new guidelines conform to the Minds Guide for Developing Clinical Practice Guidelines (2017) as much as possible. However, virtually no randomized comparative studies and meta-analyses based on such randomized studies have been conducted. Therefore, only the findings available at present were listed after conducting an exhaustive literature review of items with extremely low evidence levels and for which bodies of evidence and grades of recommendation were not evaluated. Clinical questions were set for items with a relatively large number of studies, including retrospective studies. However, since it is virtually impracticable to summarize bodies of evidence by systematic reviews, recommendation grades and evidence levels were discussed and determined by the consensus panel of the Preparatory Committee. The following were outlined: epidemiological, pathological, diagnostic, therapeutic, follow-up, and quality of life-related findings. Additionally, seven clinical questions were established to determine recommendation grades and evidence levels. We hope that these guidelines will prove to be useful to medical professionals engaged in clinical practice related to penile cancer in Japan and anticipate that critical reviews of the guidelines will lead to further refinement of the next edition.

PSMA-positive membranes secreted from prostate cancer cells have potency to transform vascular endothelial cells into an angiogenic state.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is highly expressed in poorly differentiated, metastatic, and castration-resistant prostate cancers. Recently, 68Ga-PSMA positron emission tomography/computed tomography has been successfully developed as an effective diagnostic tool for prostate cancer. However, the pathophysiological functions of PSMA in prostate tumors remain unclear. METHODS: We examined the protein expression of PSMA in tumor endothelial cells in human prostate tumors by immunohistochemistry. Prostate cancer tissues were resected by robotic surgery in 2019 at Ehime University from patients with prostate cancer. In vitro, we prepared conditioned medium (CM) derived from a PSMA-positive human prostate cancer cell line, LNCaP, cultured on collagen I gels. We then examined PSMA expression in human umbilical vascular endothelial cells (HUVECs) cultured with the CM. We assessed angiogenic activities by treatment of HUVECs with LNCaP-derived CM using a tube formation assay that mimics angiogenesis. RESULTS: Immunohistochemistry of PSMA and CD31, a marker of endothelial cells, and PSMA-expressing tumor endothelial cells were observed in 4 of 33 prostate cancer patients (12.1%). We also found that the 10,000g pellet fraction of the LNCaP-derived CM containing PSMA-positive membranes, such as microvesicles transformed HUVECs "PSMA-negative" into "PSMA-positive." Furthermore, treatment of HUVECs with the 10,000g pellet fraction of the LNCaP-derived CM significantly promoted tube formation, mimicking angiogenesis in a PSMA-dependent manner. CONCLUSIONS: Our findings revealed the existence of PSMA-positive tumor endothelial cells in human prostate tumors, which enhances tumor angiogenesis in prostate cancer tissues.

Systemic therapy for metastatic renal cell carcinoma in the first-line setting: a systematic review and network meta-analysis.

PURPOSE: Management of metastatic renal cell cancer (mRCC) has undergone a paradigm shift with immune-checkpoint inhibitors (ICI) in the first-line setting. However, direct comparative data are inadequate to inform treatment decisions. Therefore, we aimed to assess first-line therapy for mRCC and indirectly compare the efficacy and safety of currently available treatments. MATERIALS AND METHODS: Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or progression-free survival (OS/PFS) and/or adverse events (AEs) in mRCC patients were considered eligible. RESULTS: Six studies matched our eligibility criteria. For OS, pembrolizumab plus axitinib [hazard ratio (HR) 0.85, 95% credible interval (CrI) 0.73-0.98] and nivolumab plus ipilimumab (HR 0.86, 95% CrI 0.75-0.99) were significantly more effective than sunitinib, and pembrolizumab plus axitinib was probably the best option based on analysis of the treatment ranking. For PFS, pembrolizumab plus axitinib (HR 0.86, 95% CrI 0.76-0.97) and avelumab plus axitinib (HR 0.85, 95% CrI 0.74-0.98) were statistically superior to sunitinib, and avelumab plus axitinib was likely to be the preferred option based on analysis of the treatment ranking, closely followed by pembrolizumab plus axitinib. Nivolumab plus ipilimumab had significantly lower rates of serious AEs than sunitinib. CONCLUSION: Pembrolizumab plus axitinib seemed to be the most efficacious first-line agents, while nivolumab plus ipilimumab had the most favorable efficacy-tolerability equilibrium. These findings may facilitate individualized treatment strategies and inform future direct comparative trials in an expanding treatment options without direct comparison between approved drugs.

Prognostic role of the systemic immune-inflammation index in upper tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

PURPOSE: To investigate the prognostic role of the preoperative systemic immune-inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS). RESULTS: Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis. CONCLUSIONS: Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.

The Risk of New Onset Dementia and/or Alzheimer Disease among Patients with Prostate Cancer Treated with Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis.

PURPOSE: Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMed® and Web of Science™ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I2 statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months). RESULTS: A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11-1.33 and HR 1.16, 95% CI 1.09-1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07-1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77-1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97-1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69-2.79 for exposure greater than 12 months). CONCLUSIONS: Men who receive androgen deprivation therapy for prostate cancer have an increased risk of dementia and/or Alzheimer disease compared to men who do not receive androgen deprivation therapy; this was more pronounced when androgen deprivation therapy was given longer than 12 months.

The recurrence and progression risk after simultaneous endoscopic surgery of urothelial bladder tumour and benign prostatic hyperplasia: a systematic review and meta-analysis.

OBJECTIVES: To evaluate recurrence and progression risk after simultaneous endoscopic surgery of bladder cancer and benign prostatic hyperplasia (BPH), as simultaneous surgery is not an unusual scenario and theoretically simultaneous transurethral resection of bladder tumour (TURBT) and transurethral resection of the prostate (TURP) can lead to an increased risk of recurrence in the bladder neck and prostatic urethra (BN/PU). METHODS: We conducted a systematic review and meta-analysis to assess the risk of recurrence (i.e. whole bladder and/or BN/PU) and tumour progression as outcomes after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone. We queried PubMed and Web of Science database on 1 January 2020. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to the I2 statistic, respectively. RESULTS: Nine retrospective and three clinical trial studies were selected after considering inclusion and exclusion criteria. We conducted the meta-analysis on retrospective and randomised controlled trials (RCTs) separately. Eight retrospective and three RCT studies were included to assess the BN/PU recurrence risk and the summarised risk ratio (RR) was 1.02 (95% confidence interval [CI] 0.74-1.41) and 0.93 (95% CI 0.47-1.84), respectively. Five retrospective and two RCT studies were included to assess the progression risk and the summarised RR was 0.91 (95% CI 0.56-1.48) and 1.16 (95% CI 0.30-4.51), respectively. Eight retrospective and three RCT studies were included to assess the whole bladder recurrence risk and the summarised RR was 0.87 (95% CI 0.78-0.97) and 0.89 (95% CI 0.65-1.21), respectively. CONCLUSION: We did not observe any increased risk of total bladder recurrence, BN/PU recurrence, or progression after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone.

Association of De Ritis ratio with oncological outcomes in patients with non-muscle invasive bladder cancer (NMIBC).

PURPOSE: The De Ritis ratio (aspartate aminotransferase/alanine aminotransferase, DRR) has been linked to oncological outcomes in several cancers. We aimed to assess the association of DRR with recurrence-free survival (RFS) and progression-free survival (PFS) in patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: We conducted a retrospective analysis of 1117 patients diagnosed with NMIBC originating from an established multicenter database. To define the optimal pretreatment DRR cut-off value, we determined a value of 1.2 as having a maximum Youden index value. The overall population was therefore divided into two De Ritis ratio groups using this cut-off (lower, < 1.2 vs. higher, ≥ 1.2). Univariable and multivariable Cox regression analyses were used to investigate the association of DRR with RFS and PFS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). RESULTS: Overall, 405 (36%) patients had a DRR ≥ 1.2. On univariable Cox regression analysis, DRR was significantly associated with RFS (HR: 1.23, 95% CI 1.02-1.47, p = 0.03), but not with PFS (HR: 0.96, 95% CI 0.65-1.44, p = 0.9). On multivariable Cox regression analysis, which adjusted for the effect of established clinicopathologic features, DRR ≥ 1.2 remained significantly associated with worse RFS (HR:1.21, 95% CI 1.00-1.46, p = 0.04). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.683 vs. C-index = 0.681). On DCA the inclusion of DRR did not improve the net-benefit of the prognostic model. CONCLUSION: Despite the statistically significant association of the DRR with RFS in patients with NMIBC, it does not seem to add any prognostic or clinical benefit beyond that of currently available clinical factors.

Prognostic value of the preoperative albumin-globulin ratio in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

OBJECTIVE: To assess the value of preoperative albumin to globulin ratio for predicting pathologic and oncological outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy in a large multi-institutional cohort. MATERIALS AND METHODS: Preoperative albumin to globulin ratio was assessed in a multi-institutional cohort of 2492 patients. Logistic regression analyses were performed to assess the association of the albumin to globulin ratio with pathologic features. Cox proportional hazards regression models were performed for survival endpoints. RESULTS: The optimal cut-off value was determined to be 1.4 according to a receiver operating curve analysis. Lower albumin to globulin ratios were observed in 797 patients (33.6%) compared with other patients. In a preoperative model, low preoperative albumin to globulin ratio was independently associated with nonorgan-confined diseases (odds ratio 1.32, P = 0.002). Patients with low albumin to globulin ratios had worse recurrence-free survival (P < 0.001), cancer-specific survival (P = 0.001) and overall survival (P = 0.020) in univariable and multivariable analyses after adjusting for the effect of standard preoperative prognostic factors (recurrence-free survival: hazard ratio (HR) 1.31, P = 0.001; cancer-specific survival: HR 1.31, P = 0.002 and overall survival: HR 1.18, P = 0.024). CONCLUSIONS: Lower preoperative albumin to globulin ratio is associated with locally advanced disease and worse clinical outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. As it is difficult to stage disease entity, low preoperative serum albumin to globulin ratio may help identify those most likely to benefit from intensified care, such as perioperative systemic therapy, and the extent and type of surgery.

Sequential immune-targeted surgical therapy resulted in disease-free survival in a case with advanced renal cell carcinoma.

BACKGROUND: Currently, immunotherapy is indicated for patients with metastatic RCC or unresectable RCC, but there is no indication for immunotherapy in the neoadjuvant setting. We report a case in which the combined use of nivolumab and ipilimumab and sequential TKI therapy enabled surgical treatment. CASE PRESENTATION: A 71-year-old female was diagnosed with a metastatic clear-cell renal cell carcinoma with a level IV tumor thrombus. She was started on nivolumab-ipilimumab therapy, and was switched to pazopanib monotherapy because the tumor thrombus progressed within the right atrium. The tumor shrank to resectable status with sequential therapy. She then underwent right nephrectomy and thrombectomy. Pathological analysis showed 10-20% residual tumor in the primary tumor, but no viable cells in tumor thrombus. She remains clinically disease-free 1 year after surgery. CONCLUSION: This case suggests the utility of sequential immune-targeted therapy as neoadjuvant therapy in advanced renal cell carcinoma.

A low RENAL Nephrometry Score can avoid the need for the intraoperative insertion of a ureteral catheter in robot-assisted partial nephrectomy.

BACKGROUND: Intraoperative urinary collecting system entry (CSE) in robot-assisted partial nephrectomy (RAPN) may cause postoperative urinary leakage and extend the hospitalization. Therefore, identifying and firmly closing the entry sites are important for preventing postoperative urine leakage. In RAPN cases expected to require CSE, we insert a ureteral catheter and inject dye into the renal pelvis to identify the entry sites. We retrospectively analyzed the factors associated with intraoperative CSE in RAPN and explored the indications of intraoperative ureteral catheter indwelling in RAPN. METHODS: Of 104 Japanese patients who underwent RAPN at our institution from August 2016 to March 2020, 101 were analyzed. The patients were classified into CSE and non-CSE groups. The patients' background characteristics, RENAL Nephrometry Score (RNS), and surgical outcomes were analyzed. RESULTS: Intraoperative CSE was observed in 41 patients (41%). The CSE group had a significantly longer operative time, console time, ischemic time, and hospital stay than the non-CSE group. In a multivariable analysis, the N-score (odds ratio [OR] = 3.9, P < 0.05) and RNS total score excluding the L-score (OR = 3.1, P < 0.05) were associated with CSE. In a logistic regression analysis, CSE showed a moderate correlation with the RNS total score excluding the L-score (AUC 0.848, cut-off 5, sensitivity 0.83, specificity 0.73). CONCLUSION: A ureteral catheter should not be placed in patients with an RNS total score (excluding the L-score) of ≤ 4.

Predictors of Hypotension after Adrenalectomy for Pheochromocytoma.

The management of blood pressure is a significant concern for surgeons and anesthesiologists performing adrenalectomy for pheochromocytoma. We evaluated clinical factors in pheochromocytoma patients to identify the predictors of postoperative hypotension. The medical records of patients who underwent adrenalectomy for pheochromocytoma between 2001 and 2017 were retrospectively reviewed and clinical and biochemical data were evaluated. Of 29 patients, 13 patients needed catecholamine support in the perisurgical period while 16 patients did not. There were significant differences in median age, tumor size, and blood pressure drop (maxmin) between the 2 groups (68 vs 53 years old, p=0.045; 50 vs 32 mm diameter, p=0.022; 110 vs 71 mmHg, p=0.015 respectively). In univariate logistic analysis, age > 65.5 years, tumor size > 34.5 mm, urine metanephrine > 0.205 mg/day and urine normetanephrine > 0.665 mg/day were significant predictors of prolonged hypotension requiring postoperative catecholamine support. Tumor size and urine metanephrine and urine normetanephrine levels were correlated with postoperative hypotension. These predictors may help in the safe perioperative management of pheochromocytoma patients treated with adrenalectomy.

The Prognostic Impact of Intraductal Carcinoma of the Prostate: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aimed to assess the prognostic impact of intraductal carcinoma of the prostate in patients with prostate cancer. MATERIALS AND METHODS: A systematic search was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. We searched PubMed®, Web of Science™, the Cochrane Library and Scopus® up to October 2019. The end points were biochemical recurrence-free, cancer specific and overall survival. RESULTS: We identified 32 studies with 179,766 patients. A total of 31 studies containing 179,721 patients with localized and advanced prostate cancer were eligible for meta-analysis. In localized prostate cancer intraductal disease was associated with adverse outcomes including lower biochemical recurrence-free survival (pooled HR 2.09, 95% CI 1.75-2.50) and cancer specific survival (pooled HR 2.93, 95% CI 2.25-3.81). In advanced prostate cancer overall survival was lower in patients with vs without intraductal disease (pooled HR 1.75, 95% CI 1.43-2.14). Subgroup analysis by specimen type revealed that intraductal carcinoma of the prostate is a significant negative prognostic factor in both biopsies and prostatectomy specimens. Moreover, subgroup analyses based on the histopathological definitions of intraductal carcinoma of the prostate indicated that intraductal disease was significantly associated with lower biochemical recurrence-free, cancer specific and overall survival for almost all definitions. CONCLUSIONS: Intraductal disease is a histopathological feature of biologically and clinically aggressive prostate cancer. It confers worse oncologic outcomes in both localized and advanced prostate cancer, whether assessed in biopsy or prostatectomy specimen. The pathologist should assess for and report on the presence of intraductal disease in all prostate specimens. The urologist and radiation oncologist should consider this adverse feature in their clinical decision making.

Bladder-preserving strategies for Bacillus Calmette-Guérin unresponsive non-muscle invasive bladder cancer; where are we and what will be expected?

PURPOSE OF REVIEW: Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) is a new definition including patients who failed intravesical BCG therapy and should not receive more BCG because of the very low efficacy and disproportionately poor prognosis. Radical cystectomy as the standard of care for these patients is associated with significant morbidity and altered quality of life. Therefore, the FDA has accepted phase II single-arm studies as a threshold to approve new agents in this setting. RECENT FINDINGS: Efforts to find an effective and safe bladder sparing strategy for BCG unresponsive patients have not been successful yet. Studies that assess nanoparticle-bound, combination or device-assisted intravesical chemotherapy to increase drug delivery and efficacy have been partly promising but suffer from limitations. Systemic immunotherapy such as checkpoint inhibitors therapy PD1/PDL1 and intravesical immunotherapy such as rAd-IFN/Syn3 have shown satisfactory efficacy so far. SUMMARY: Although this is much effort and enthusiasm, no bladder-sparing strategy has met the criteria set for the successful alternative to radical cystectomy in BCG unresponsive NMIBC. For BCG unresponsive patients who refuse or are unfit for radical cyctectomy, there is new hope arising with novel strategies limiting the threshold for clinical use and a multitude of promising agents in clinical trials.

Prognostic value of testosterone for the castration-resistant prostate cancer patients: a systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to assess the prognostic value of testosterone in patients with castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: PubMed, Web of Science, and Scopus databases were systematically searched until December 2019, according to the Preferred Reporting Items for Systemic Review and Meta-analysis statement. The endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: We identified 11 articles with 4206 patients for systematic review and nine articles with 4136 patients for meta-analysis. Higher testosterone levels were significantly associated with better OS (pooled HR 0.74, 95% CI 0.58-0.95) and better PFS (pooled HR 0.51, 95% CI 0.30-0.87). Subgroup analyses based on the treatment type revealed that higher testosterone levels were significantly associated with better OS in CRPC patients treated with androgen receptor-targeted agents (ARTAs) (pooled HR 0.64, 95% CI 0.55-0.75), but not in those treated with chemotherapy (pooled HR 0.78, 95% CI 0.53-1.14). CONCLUSION: This meta-analysis demonstrated that the PFS and OS were significantly greater in patients with CRPC in those with higher testosterone levels than that of those with lower testosterone levels. In the subgroup analyses, lower testosterone levels were a consistently poor prognostic factor for OS in patients treated with ARTAs, but not in those treated with chemotherapy. Therefore, higher testosterone levels could be a useful biomarker to identify patient subgroups in which ARTAs should be preferentially recommended in the CRPC setting.