Prospective evaluation of a urinary biomarker panel to detect and predict recurrence of non-muscle-invasive bladder cancer.

PURPOSE: To perform a feasibility phase study of a panel of putative protein biomarkers and determine whether it can identify and predict tumor recurrence in patients with non-muscle-invasive bladder cancer (NMIBC) on follow-up. METHODS: We prospectively analyzed the urine of 152 patients previously treated for NMIBC. Quantitative expression of plasminogen activator inhibitor-1 (PAI-1), DJ-1, apolipoprotein A-I (apoA-1), matrix metallopeptidase-9 (MMP-9), and interleukin-8 (IL-8) was assessed by enzyme-linked immunosorbent assay and compared amongst patients with and without bladder cancer recurrence at urine collection and during 3 years of follow-up. Tumor recurrence was confirmed by pathologic analysis. We performed a prediction analysis, excluding patients with recurrence at the start of the study, and assessed the influence of previous use of intravesical BCG on the level of biomarkers. RESULTS: Median follow-up time was 47 months (interquartile range 39-50 months). Sixteen patients (10.5%) were diagnosed with recurrence at the start of the study, and 21 (15.4%) were diagnosed during the study. Three biomarker proteins (apoA-1, MMP-9, and IL-8) appear to hold diagnostic potential [odds ratio (OR) = 12.9; 95% CI 3.5-47.4]; while, PAI-1 and IL-8 predict recurrence (OR = 4.1; 95% CI 1.4-11.4). Previous use of intravesical BCG did not affect biomarker levels. CONCLUSION: In the feasibility phase, the panel of urine biomarkers analyzed detected and predicted recurrence of NMIBC and provided reliable results in patients who had previously used intravesical BCG. Validation studies are required to confirm the panel clinical utility.

Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer.

OBJECTIVE: To evaluate the relation between serum total testosterone (TT) and prostate cancer (PCa) grade and the effect of race and demographic characteristics on such association. METHOD: We analyzed 695 patients undergoing radical prostatectomy (RP), of whom 423 had serum TT collected. Patients were classified as having hypogonadism or eugonadism based on two thresholds of testosterone: threshold 1 (300 ng/dL) and threshold 2 (250 ng/dL). We evaluated the relation between TT levels and a Gleason score (GS) ≥ 7 in RP specimens. Outcomes were evaluated using univariate and multivariate analyses, accounting for race and other demographic predictors. RESULTS: Out of 423 patients, 37.8% had hypogonadism based on the threshold 1 and 23.9% based on the threshold 2. Patients with hypogonadism, in both thresholds, had a higher chance of GS ≥ 7 (OR 1.79, p=0.02 and OR 2.08, p=0.012, respectively). In the multivariate analysis, adjusted for age, TT, body mass index (BMI) and race, low TT (p=0.023) and age (p=0.002) were found to be independent risk factors for GS ≥ 7. Among Black individuals, low serum TT was a stronger predictor of high-grade disease compared to White men (p=0.02). CONCLUSION: Hypogonadism is independently associated to higher GS in localized PCa. The effect of this association is significantly more pronounced among Black men and could partly explain aggressive characteristics of PCa found in this race.

Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer / Baixa testosterona sérica é prognóstica de doença de alto grau em pacientes com câncer de próstata

Summary Objective: To evaluate the relation between serum total testosterone (TT) and prostate cancer (PCa) grade and the effect of race and demographic characteristics on such association. Method: We analyzed 695 patients undergoing radical prostatectomy (RP), of whom 423 had serum TT collected. Patients were classified as having hypogonadism or eugonadism based on two thresholds of testosterone: threshold 1 (300 ng/dL) and threshold 2 (250 ng/dL). We evaluated the relation between TT levels and a Gleason score (GS) ≥ 7 in RP specimens. Outcomes were evaluated using univariate and multivariate analyses, accounting for race and other demographic predictors. Results: Out of 423 patients, 37.8% had hypogonadism based on the threshold 1 and 23.9% based on the threshold 2. Patients with hypogonadism, in both thresholds, had a higher chance of GS ≥ 7 (OR 1.79, p=0.02 and OR 2.08, p=0.012, respectively). In the multivariate analysis, adjusted for age, TT, body mass index (BMI) and race, low TT (p=0.023) and age (p=0.002) were found to be independent risk factors for GS ≥ 7. Among Black individuals, low serum TT was a stronger predictor of high-grade disease compared to White men (p=0.02). Conclusion: Hypogonadism is independently associated to higher GS in localized PCa. The effect of this association is significantly more pronounced among Black men and could partly explain aggressive characteristics of PCa found in this race.

Resumo Objetivo: Avaliar a relação entre testosterona sérica total (TT) e grau do câncer de próstata (CP) e o efeito da raça e de características demográficas sobre essa associação. Método: Foram analisados 695 pacientes submetidos a prostatectomia radical (PR), dos quais 423 tinham medidas dos níveis séricos de TT. Os pacientes foram classificados como portadores de hipogonadismo ou eugonadismo com base em dois limites de testosterona: limite 1 (300 ng/dL) e limite 2 (250 ng/dL). Avaliou-se a relação entre nível de TT e escore Gleason (GS) ≥ 7 em amostras de PR. Os resultados foram avaliados por análises univariada e multivariada, com ajuste para raça e outros fatores prognósticos demográficos. Resultados: Do total de 423 pacientes, 37,8% apresentavam hipogonadismo com base no limite 1, e 23,9% com base no limite 2. Os pacientes com hipogonadismo, independentemente do limite de referência, tiveram uma chance maior de GS ≥ 7 (OR 1,79, p=0,02 e OR 2,08, p=0,012, respectivamente). Na análise multivariada, após ajuste para idade, TT, índice de massa corporal (IMC) e raça, baixo TT (p=0,023) e idade (p=0,002) foram considerados fatores de risco independentes para GS ≥ 7. Entre os indivíduos negros, baixo TT sérico foi mais preditivo de doença de alto grau em comparação com os brancos (p=0,02). Conclusão: O hipogonadismo é independentemente associado a escores mais altos de GS no CP localizado. O efeito dessa associação é significativamente mais pronunciado entre homens negros, o que poderia explicar, em parte, as características agressivas do CP observadas nessa população.

Carcinosarcoma of the bladder following local schistosomiasis infection.

A young patient from central Africa presented acute renal insufficiency due to extrinsic compression of the distal ureters by a pelvic mass. After initial medical management, a biopsy revealed poorly differentiated bladder cancer and Schistosoma haematobium eggs embedded in the bladder wall. The initial workup showed evidence of locoregional disease. Radical cystectomy with an incontinent urinary diversion was performed with no complications. Carcinosarcoma of the bladder was diagnosed by pathological analysis of the surgical specimen. After a short follow-up, the patient was readmitted presenting with lung and bone metastases. At 60 days after diagnosis, he died of respiratory insufficiency caused by pulmonary metastatic disease.