ABSTRACT
PURPOSE: To evaluate the impact of presenting symptoms on survival in a contemporary series of patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: We prospectively recorded data on the presenting symptoms, pathology, and RCC-specific survival of 633 consecutive RCC patients who underwent surgery between 2003 and 2012. RESULTS: Four hundred thirty-three RCCs (68%) were incidental, 111 (18%) were associated with local symptoms, and 89 (14%) were associated with systemic symptoms. Among those with incidental RCC, 317 patients (73%) were completely asymptomatic and 116 patients (27%) presented with symptoms not related to the tumor. During a median follow-up interval of 40 months (interquartile range: 39 to 69 months), 77 patients died from RCC. In univariate analyses, symptom classification was significantly associated with RCC-specific survival (p<0.001). Patients with incidental RCC and unrelated symptoms tended to have worse prognosis than did patients who were completely asymptomatic, although this difference was not statistically significant (p=0.057). The symptom classification was associated with advanced TNM stages (p<0.001) and grade (p<0.001). CONCLUSIONS: This study confirms that presenting symptoms are associated with tumor characteristics and survival. The majority of RCCs are diagnosed incidentally in patients without any symptoms or with symptoms not related to RCC. Patients in the latter group tend to have a worse prognosis than do patients who are completely asymptomatic. With the increasing number of incidentally diagnosed RCCs, substratification of patients with incidental tumors may be prognostically relevant.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Carcinoma, Renal Cell/diagnosis , Follow-Up Studies , Kaplan-Meier Estimate , Kidney Neoplasms/diagnosis , Neoplasm Staging , Nephrectomy/methods , Prognosis , Prospective StudiesABSTRACT
Prostate cancer [PCa] represents a significant health burden and the high prevalence and natural course of the untreated disease make PCa ideal for screening and early detection. The aim of this review is to give an overview of the recent evidence on biomarkers for screening and early detection of PCa. A review of the current literature on prostate-specific antigen [PSA] and novel biomarkers in PCa diagnosis and screening was conducted using MEDLINE/PubMed to identify relevant publications. PSA is currently the main biomarker for PCa screening and diagnosis, and two out of three recent randomized controlled trials on PSA screening for PCa showed a 20-40% risk reduction of PCa-specific mortality in the screened group. In contrast, one study did not show any beneficial effect of PSA screening. Although each study had flaws, the study that reported no benefit from PSA screening had a high contamination rate in the control group and non-compliance in the screening group. However, PCa screening was associated with overdiagnosis, which led to overtreatment. Therefore, there is a need for novel biomarkers that are more specifically associated with PCa and its biological and clinical behaviour. Several such biomarkers are currently being investigated as an adjunct to PSA; however, none can currently replace PSA. Among novel biomarkers, PCa antigen 3 [PCA3] and TMPRSS2-ERG gene fusions appear to be most promising and, currently, PCA3 is reported as the more efficient diagnostic test in patients who have had a previous negative biopsy
ABSTRACT
To evaluate the long-term prognostic value of the combination of the EORTC risk calculator and proapoptotic, antiapoptotic, proliferation, and invasiveness molecular markers in predicting the outcome of intermediate- and high-risk non-muscle-invasive bladder cancer [NMIBC] treated with intravesical Bacille Calmette-Gurin [BCG] therapy. This study included 42 patients accrued prospectively presenting with intermediate- to high-risk NMIBC [high-grade T1 tumors or multiple rapidly recurrent tumors refractory to intravesical chemotherapy] treated with transurethral resection [TUR] and BCG. TUR samples were analyzed for the molecular markers p53, p21 waf1/cip, Bcl-2, CyclinD1, and metallothionein 9 [MMP9] using immunohistochemistry. Frequency of positivity, measured as a percentage, was assessed alone or in combination with EORTC risk calculator, for interaction with outcome in terms of recurrence and progression using univariate analysis and Kaplan-Meier survival curves. Median follow-up was 88 months [mean, 99; range, 14-212 months]. The overall recurrence rate was 61.9% and progression rate was 21.4%. In univariate analysis, CyclinD1 and EORTC risk groups were significantly associated with recurrence [P value 0.03 and 0.02, respectively], although none of the markers showed a correlation to progression. In combining EORTC risk groups to markers expression status, high-risk group associated with positive MMP9, Bcl-2, CyclinD1, or p21 was significantly correlated to tumor recurrence [log rank P values <0.001, 0.03, 0.02, and 0.006, respectively] and when associated with positive MMP9 or p21, it was significantly correlated to progression [log rank P values 0.01 and 0.04, respectively]. Molecular markers have a long-term prognostic value when combined with EORTC scoring system and they may be used to improve the predictive accuracy of currently existing scoring system. Larger series are needed to confirm these findings
ABSTRACT
El carcinoma urotelial de la vejiga (CUV) tiene una tasa de recurrencia muy alta y por tanto requiere seguimiento por toda la vida, consistiendo tradicionalmente en cistoscopias y citologías seriadas. Ambos test son invasivos y caros, con considerable variabilidad inter usuario e interinstitucional. Además la sensibilidad de la citología para detectar tumores de bajo grado es baja. En consecuencia ha habido una investigación muy activa en biomarcadores urinarios que pudieran, ya sea suplementar o reemplazar estos test. En este momento, hay sólo seis test basados en orina que están aprobados por la FDA en el seguimiento del CUV (BTA STAT y TRAK, Inmuno Cyt, NMP22, Urovysion). Sin embargo, se está estudiando una gran variedad de otros biomarcadores. En esta revisión, describimos la racionalidad y enfatizamos los hallazgos más recientes y relevantes de los biomarcadores aprobados por la FDA, tales como el Antígeno Tumoral de Vejiga, InmunoCyt, la Matriz Nuclear de la Proteína-22 y la Hibridización Fluorescente in situ, como también aquellos biomarcadores en investigación más prometedores (test UCB Urinario, BLCA-1, BLCA-4, Acido hialurónico, Hialuronidasa, el antígeno Lewis X, análisis micro satélite, Quanticyt, Fas soluble, Survivina, Telomerasa y CK20). Se discuten los fundamentos biológicos, las metodologías y el desempeño diagnóstico de los principales biomarcadores y también sus principales características comparadas con la citología urinaria. La mayoría de los estudios comparativos han mostrado que los biomarcadores no invasivos tienen igual o mayor sensibilidad para la detección del CUV que la citología, aun en cánceres de alto grado. Sin embargo, ninguno de estos test llenan todos los criterios de un biomarcador tumoral ideal. Se requiere aún una estandarización mejorada y automatización de los métodos, como también una validación prospectiva a gran escala en poblaciones heterogéneas de pacientes. Sin embargo, pese a la utilización...
Urothelial Carcinoma (UC) is highly recurrent and therefore lifetime follow up is mandatory. Standard follow up is done with serial urinary cytology and cystoscopy. Both tests are invasive and expensive. Also, the results are highly variable among different institutions. Furthermore, urine cytology shows poor sensitivity in low grade tumors. For these reasons, there is active research looking for urine biomarkers that could replace current standard tests. At present, there are 6 FDA-approved urine based tests for UC follow up: BTA, STAT and TRAK; Immunocyt, NMP 22, Urovision . In this review, we describe FDA-approved tests like Bladder Tumor Antigen, Immunocyt, Protein22 Nuclear Matrix and FISH. Also, we describe some promising markers like Urinary UCB test, BLCA-1, BLCA-4, Hyaluronic Acid, Hyaluronidase, Lewis X Antigen, Microsatelite Analysis, Quanticyt, Soluble Fas, Survivine, Telomerase and CK20. Biological basis, methods and diagnostic performance are discussed. Most studies show that non-invasive biomarkers are equal or better than urinary cytology for the diagnosis of UC. However, none of them fulfill the criteria for an ideal biomarker. These new tests need to be validated in prospective studies using large groups of patients. The goal is to identify a biomarker that could eventually replace or complement urinary cytology. In the future these biomarkers will be used for screening in high risk patients or to predict recurrences. In that way, the use of invasive tests will decrease.