Delays in radical cystectomy for muscle-invasive bladder cancer.

BACKGROUND: Delays from the diagnosis of muscle-invasive bladder cancer (MIBC) to radical cystectomy (RC) longer than 12 weeks result in higher mortality and shorter progression-free survival. This study sought to identify factors associated with RC delays and to determine whether delays in care in the current treatment paradigm, which includes neoadjuvant chemotherapy (NAC), affect survival. METHODS: Subjects with American Joint Committee on Cancer stage II urothelial carcinoma of the bladder who underwent RC from 2004 to 2012 were identified from the linked Surveillance, Epidemiology, and End Results national cancer registry and the Medicare claims database and were stratified into RC groups with or without NAC. Cox multivariable proportional hazard models and multivariable logistic regression models assessed the significance of delays in RC for survival and identified independent characteristics associated with RC delays, respectively. RESULTS: This study identified 1509 patients with MIBC who underwent RC during the study period. In comparison with timely surgery, delays in RC increased overall mortality, regardless of the use of NAC (hazard ratio [HR] without NAC, 1.34; 95% confidence interval [CI], 1.03-1.76; HR after NAC, 1.63; 95% CI, 1.06-2.52). Patients proceeding to RC without NAC had higher odds of delayed care if they lived in a high-poverty neighborhood (odds ratio [OR], 1.37; 95% CI, 1.01-2.08) or nonmetropolitan area (OR, 1.61; 95% CI, 1.01-2.55), were men (OR, 2.22; 95% CI, 1.25-4.00), or required a provider transfer for bladder cancer care (OR, 1.82; 95% CI, 1.10-3.03). CONCLUSIONS: Delays in care from the time of either the initial diagnosis or the completion of NAC to RC are associated with worse overall survival among patients with MIBC. Timely surgery is fundamental in the treatment of MIBC, and this necessitates attention to disparities in access to complex surgical care and care coordination.

[Urologic malignancies in renal transplant candidates and recipients]. / Transplantation rénale et cancers urologiques.

OBJECTIVE: To review epidemiology and management of urologic neoplasms in renal transplant candidates and recipients. MATERIAL AND METHODS: Relevant publications were identified through Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) database using the following keywords, alone or in association, "neoplasms"; "prostate cancer"; "renal carcinoma"; "renal transplantation"; "transitional carcinoma"; "waiting list". Articles were selected according to methods, language of publication and relevance. A total of 7730 articles were identified including 781 for solid tumors, 1565 for renal cell carcinoma (RCC), 2674 for prostate cancer (Pca), 385 for transitional carcinoma (TC) and 56 for testicular cancer; after careful selection, 221 publications were eligible for our review. RESULTS: Renal transplant candidates and recipients are at higher risk of urologic neoplasms than general population, but prostate cancer has similar features. Thus, all therapeutic options are valid. Conversely to radiation therapy, radical prostatectomy provides precise staging and immediate affirmation of therapeutic success. Lymph nodes dissection needs to be discussed; systematic screening using PSA level and digital rectal examination should be offered in this specific population. RCC arising in native kidneys are usually low grade and stage and require total nephrectomy. In transplant candidates, there is no need to delay transplantation after treatment of low risk RCC according to published predictive nomograms. RCC of the allograft are rare, with a prevalence of 0.2 to 05% with a dialysis free survival ranging from 40 to 75% at 21.5 to 43 months. Treatment options are nephron sparing surgery, percutaneous ablation and immediate or deferred transplantectomy. Conversely to RCC or PCa, TC present with more unfavorable features as general population. Their management faces specific difficulties such as lower efficacy of BCG instillation or the technical challenge of urinary diversion. CONCLUSION: Application of appropriate indication for transplantectomy relies on benefit-risk balance between the interruption of immunosuppressive agents versus survival and quality of life impairment after returning to dialysis. No robust recommendation exists regarding switch of immunosuppressive drugs. Cancer predictive factors and access to a subsequent transplantation are key decisive elements.

Genomic and Clinical Prognostic Factors in Patients With Advanced Urothelial Carcinoma Receiving Immune Checkpoint Inhibitors.

BACKGROUND: Recently data suggest that telomerase reverse transcripatase (TERT) promoter mutations portend superior outcomes with immune checkpoint inhibitor (ICI) therapy in mUC. In our retrospective analysis from 2 tertiary cancer centers, we assessed the predictive role of TERT mutations along with other parameters. METHODS: Patient registries were queried for patients treated with ICI for mUC with available genomic and clinical data. Select clinical and laboratory parameters, in addition to primary tumor site, histology, treatment modality, and setting were recorded. Tumor mutational burden (TMB), and mutational status of TERT, CDKN2A, CDKN2B, TMB, TP53, RB1, KMT2D, ARID1A, ERBB2, KDM6A, PIK3CA, FGFR3, and ATM were noted. Univariate analysis of significance concerning overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) was conducted. RESULTS: In total, 113 patients were found to meet inclusion criteria. In our study, ORR was 55%, median PFS was 5.1 months (0.2-71.8), and median OS was 13.4 months (0.2-84.8). On univariate analysis, female sex, NLR>5, and ATM mutation were associated with inferior PFS and OS, whereas upper tract primary disease and ECOG score ≥ 2 were associated with worse OS. On multivariate analysis, NLR >5 was associated with worse PFS and OS whereas upper tract primary disease, albumin <3.4 g/dL, hemoglobin <10 g/dL and ATM mutation were significantly associated with worse OS on multivariate analysis. No significant differences were seen in ORR, PFS, or OS regarding TERT promoter mutations. CONCLUSION: TERT promoter mutations were not significantly associated with any difference in outcome in patients treated with ICI.

Upper tract urothelial carcinoma with Oligometastasis to the right ventricle, surgical considerations, and management.

Right ventricular (RV) metastasis from an upper tract urothelial carcinoma without inferior vena cava or right atrial involvement is an extremely rare event which highlights the heterogeneity of this disease process. We report a case of a 43-year-old man presenting for long-standing hematuria and left flank pain. Computed tomography revealed a left renal mass with para-aortic lymphadenopathy, in addition to a potential mass in the RV. The mass involving the RV was confirmed on subsequent cardiac evaluation with magnetic resonance imaging (MRI) and echocardiography. After discussion in a multidisciplinary tumor board, the patient underwent a left nephrectomy, regional lymphadenectomy, and excision of metastatic RV tumor with bovine patch reconstruction. Final pathology reported invasive urothelial carcinoma in the left kidney with involvement of regional para-aortic lymph nodes and metastatic tumor in the RV (T4N3M1, AJCC 8th edition). The patient did well postoperatively and completed adjuvant Cisplatin-Gemcitabine systemic chemotherapy. This is an important addition to the literature as it highlights the aggressive and heterogeneous nature of urothelial carcinoma and the utility of cardiac MRI in surgical planning.

Transitional cell carcinoma in untreated adult bladder exstrophy: A rare case report.

Untreated adult bladder exstrophy is a very rare entity and has a higher risk of developing bladder cancer. A 41-year old man with acute kidney injury and bilateral hydronephrosis was consulted to Urology Division. Examination revealed bladder exstrophy with suspected malignancy. The incisional biopsy result showed transitional cell carcinoma which is the most common bladder cancer, but extremely rare in bladder exstrophy. Radical cystectomy and urinary diversion with double-barrel ureterocutaneostomy were conducted. Abdominal defect was closed with surgical mesh application and rotational skin flap. The patient was well recovered with improved quality of life.

Femoral metastasis in previously treated bladder cancer patient: A case report.

Although treated appropriately, bladder cancer can recur and metastasize. We are reporting the case of a patient with a well-cured bladder cancer who presented after 14 months with femoral pain which turned out to be a bony metastasis. The patient underwent surgical excision followed by chemotherapy.

Systematic Review of the Role of BCG in the Treatment of Urothelial Carcinoma of the Prostatic Urethra.

BACKGROUND: In patients with non-invasive urothelial carcinoma of the prostatic urethra (PUC), treatment with Bacillus Calmette-Guérin (BCG) could be beneficial. OBJECTIVE: To assess the response rates to BCG in the different tumor stages, to describe the clinical impact of transurethral resection of the prostate (TURP) before BCG treatment, and to review the side effects of BCG treatment for PUC. METHODS: A systematic search was conducted using the PubMed database to identify original studies between 1977 and 2019 reporting on PUC and BCG. RESULTS: Of a total of 865 studies, ten were considered for evidence synthesis. An indication for BCG treatment was found in non-stromal invasive stages (Tis pu, Tis pd) and in stromal infiltrating cases (T1) of primary and secondary PUC when transitional cell carcinoma was the histology of origin. Studies including patients treated with TURP before BCG showed a better local response in the prostatic urethra with a higher disease free survival (DFS) (80-100% vs. 63-89%) and progression free survival (PFS) (90-100% vs. 75-94%) than patients in studies in which no TURP was performed. However, this difference in recurrence and progression in the prostate neither affected the total PFS (57-75% vs. 58-93%), nor the disease specific survival (70-100% vs. 66-100%). CONCLUSIONS: The use of resection loop biopsies of the prostatic urethra in appropriate cases during the primary work-up for suspected PUC, as well as the use of the current TNM classification for PUC, need to be improved. BCG therapy for non-stromal invasive stages of PUC show a good local response. Local response is further improved by a TURP before BCG therapy, although the overall prognosis does not seem to be affected. Further evidence for BCG treatment in the rare cases of stromal invasive PUC is needed. Specific side effects of BCG treatment for PUC are not reported.

Therapeutic strategies for upper tract urothelial carcinoma.

INTRODUCTION: Many controversies exist regarding the appropriate management of patients with upper tract urothelial carcinoma (UTUC), including staging, surgical management, use of systemic therapy, and prevention of bladder recurrence. Due to the rarity of this condition, high-level evidence is often lacking and in many cases guidelines are extrapolated from existing evidence on urothelial bladder cancer. Areas covered: This review paper summarizes the evidence on proper diagnosis and staging, surgical techniques, prevention of bladder recurrences, the use of local or systemic treatments in both neoadjuvant and adjuvant settings as well as special consideration for hereditary UTUC. Expert commentary: UTUC is a rare malignancy and slow progress is being made in the acquisition of high-quality evidence in this field. Treatments that facilitate preservation of the kidney are being explored such as advanced endoscopic techniques or partial resection of ureteral disease with seemingly acceptable oncological results. Further prospective evidence is needed.

Microcystic transitional cell carcinoma: a rare tumor of the urinary bladder.

Microcystic urothelial carcinoma is a rare variant of invasive transitional cell carcinoma recognized by the WHO classification. It is characterized by its deceptively benign appearance. The clinical course of this uncommon variety of carcinoma is not well known and their histological and immunohistological features are not well defined. We report a case of a 37-year-old man with a microcystic transitional cell carcinoma of the urinary bladder. He was diagnosed 4 years ago with cystitis glandularis lesions and nephrogenic adenoma. Through this observation we will try to define the clinical and pathological features of this uncommon tumor which must be differentiated from a number of proliferative lesions of the urothelium. The poor prognosis and aggressiveness of this tumor seems to be related to a higher stage and grade at diagnosis.

Primary carcinoma of the ureteral stump following radical nephrectomy for renal cell carcinoma: A case report and literature review.

The occurrence of primary carcinoma of the ureteral stump following radical nephrectomy for renal cell carcinoma is extremely rare; 7 patients with the disease have been reported previously. All these patients were males with transitional cell carcinoma. The current study reports the case of a 61-year-old woman, who presented with gross hematuria following a radical nephrectomy for local clear cell renal carcinoma. A computed tomography scan revealed the presence of a mass on the ureteral stump. The patient underwent a left ureteral stump and bladder cuff excision. The histological diagnosis was high-grade transitional cell carcinoma of the ureteral stump, with focal interstitial cancer cell infiltrates. There was no evidence of recurrence during a follow-up period of 35 months. In addition, the present study reviewed the literature for previous patients with ureteral stump carcinoma following a radical nephrectomy for renal cell carcinoma; 7 previous patients with the disease were identified. The present study suggests that, if patients who have previously undergone a radical nephrectomy for renal cell carcinoma present with hematuria, the possibility of ureteral stump carcinoma should be considered, particularly in East Asian countries. The existence or a history of bladder carcinoma should be considered as a high-risk factor for developing ureteral stump carcinoma. A ureteral stump and bladder cuff excision should be performed once ureteral stump carcinoma is diagnosed.

[Aristolochic acid nephropathy ("Chinese herb nephropathy")]. / Néphropathie aux acides aristolochiques (« néphropathie aux herbes chinoises ¼).

Aristolochic acid nephropathy is a renal disease of toxic origin characterized by a progressive interstitial fibrosis and frequently associated with urinary tract cancer. It was initially reported in Belgium after the intake of slimming pills containing root extracts of a Chinese herb, Aristolochia fangchi. In the following decades, numerous cases have been reported worldwide, particularly in Asian countries. Several experimental models of aristolochic acid nephropathy (AAN) have been designed. They confirm the causal link between AA exposure and the onset of acute and chronic renal toxicity, as well as urinary tract cancer. These experimental models offer the opportunity to study the mechanisms of renal interstitial fibrosis and carcinogenesis. In terms of public health, the history of this nephropathy demonstrates that it is mandatory to submit all "natural medicinal products" to the same controls of efficacy, toxicity and conformity applied to the classical drugs derived from the pharmaceutical producers. Any unusual observation of renal failure and/or cancer of the urinary tract should lead to a questioning about any prior exposure to AA. The confirmation of the ingestion of AA containing compounds by phytochemical analysis is not always feasible. However, the renal biopsy remains a crucial diagnostic point through the demonstration of a hypocellular interstitial fibrosis with a decreasing corticomedullary gradient, mostly in advanced cases of kidney disease. Moreover, the detection of AA-related DNA adducts within a renal or urothelial tissue sample could confirm the prior AA exposure. The persistence of these specific DNA adducts in renal tissue is very long (up to 20 years). Finally, considering the highly carcinogenic properties of AA, a systematic endo-urological screening is absolutely necessary.

Survival of patients with squamous cell malignancies of the upper urinary tract.

BACKGROUND: Carcinomas of the renal pelvis and ureter are rare diseases, accounting for only about 1% of all urogenital malignancies. Previous reports suggest that squamous cell histology is associated with inferior survival. We present the largest population based analysis to date of survival in patients with upper urinary tract malignancies. METHODS: We analyzed the Surveillance, Epidemiology and End Results database for cancer specific survival rates in patients with renal pelvis and ureteral malignancies who were diagnosed between 1973 and 2003 in the SEER catchment geographic areas. The primary exposure of interest was the underlying histology, squamous cell versus transitional cell differentiation. We performed descriptive statistics, non parametric survival analysis, and cox proportional hazard analysis. RESULTS: We identified 13,213 eligible patients, 7,716 renal pelvis and 5,497 ureteral carcinomas. Among this cohort, 179 patients had squamous cell carcinoma (SCC), 12,395 had transitional cell carcinoma (TCC), including 121 papillary, and 619 had other histologies. Overall, patients with SCC histology fared worse. The median overall survival time was 10 months for SCC and 63 months for TCC. The cox analysis revealed a HR 3.7 (95% CI 3.0-4.5) for SCC when compared to TCC and corrected for decade of diagnosis, age, gender, prior treatment, and race. The difference between the two groups was entirely attributable to survival differences in patients with loco-regional disease. However, when stratified by lymph node involvement this difference disappeared for patients with locally involved lymph nodes (P = 0.84) and for patients with clear lymph nodes (P = 0.92). CONCLUSIONS: SCCs of the upper urinary tract present at a higher clinical stage and appear to represent more aggressive disease when compared to other histologies. However, when appropriately staged according to lymph node status, the survival of TCC and SCC of the upper urinary tract is identical when compared stage by stage.