The role of TMPRSS2:ERG in molecular stratification of PCa and its association with tumor aggressiveness: a study in Brazilian patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Reabilitação do assoalho pélvico em pacientes com incontinência urinária pós prostatectomia radical

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Valor prognóstico da avaliação urodinâmica e da força do assoalho pélvico na incontinência urinária pós prostatectomia radical

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The accuracy of pathological data for the prediction of insignificant prostate cancer

Introduction: The widespread screening programs prompted a decrease in prostate cancer stage at diagnosis, and active surveillance is an option for patients who may harbor clinically insignificant prostate cancer (IPC). Pathologists include the possibility of an IPC in their reports based on the Gleason score and tumor volume. This study determined the accuracy of pathological data in the identification of IPC in radical prostatectomy (RP) specimens. Materials and Methods: Of 592 radical prostatectomy specimens examined in our laboratory from 2001 to 2010, 20 patients harbored IPC and exhibited biopsy findings suggestive of IPC. These biopsy features served as the criteria to define patients with potentially insignificant tumor in this population. The results of the prostate biopsies and surgical specimens of the 592 patients were compared. Results: The twenty patients who had IPC in both biopsy and RP were considered real positive cases. All patients were divided into groups based on their diagnoses following RP: true positives (n = 20), false positives (n = 149), true negatives (n = 421), false negatives (n = 2). The accuracy of the pathological data alone for the prediction of IPC was 91.4%, the sensitivity was 91% and the specificity was 74%. Conclusion: The identification of IPC using pathological data exclusively is accurate, and pathologists should suggest this in their reports to aid surgeons, urologists and radiotherapists to decide the best treatment for their patients.

Surrogate endpoints for prostate cancer-specific mortality after radiotherapy and androgen suppression therapy in men with localised or locally advanced prostate cancer: an analysis of two randomised trials

Background Androgen suppression therapy and radiotherapy are used to treat locally advanced prostate cancer. 3 years of androgen suppression confers a small survival benefit compared with 6 months of therapy in this setting, but is associated with more toxic effects. Early identification of men in whom radiotherapy and 6 months of androgen suppression is insufficient for cure is important. Thus, we assessed whether prostate-specific antigen (PSA) values can act as an early surrogate for prostate cancer-specific mortality (PCSM). Methods We systematically reviewed randomised controlled trials that showed improved overall and prostate cancer-specific survival with radiotherapy and 6 months of androgen suppression compared with radio therapy alone and measured lowest PSA concentrations (PSA nadir) and those immediately after treatment (PSA end). We assessed a cohort of 734 men with localised or locally advanced prostate cancer from two eligible trials in the USA and Australasia that randomly allocated participants between Feb 2, 1996, and Dec 27, 2001. We used Prentice criteria to assess whether reported PSA nadir or PSA end concentrations of more than 0.5 ng/mL were surrogates for PCSM. Findings Men treated with radiotherapy and 6 months of androgen suppression in both trials were significantly less likely to have PSA end and PSA nadir values of more than 0.5 ng/mL than were those treated with radiotherapy alone (p<0.0001). Presence of candidate surrogates (ie, PSA end and PSA nadir values >0.5 ng/mL) alone and when assessed in conjunction with the randomised treatment group increased risk of PCSM in the US trial (PSA nadir p=0.0016; PSA end p=0.017) and Australasian trial (PSA nadir p<0.0001; PSA end p=0.0012). In both trials, the randomised treatment group was no longer associated with PCSM (p >= 0.20) when the candidate surrogates were included in the model. Therefore, both PSA metrics satisfied Prentice criteria for surrogacy. Interpretation After radiotherapy and 6 months of androgen suppression, men with PSA end values exceeding 0.5 ng/mL should be considered for long-term androgen suppression and those with localised or locally advanced prostate cancer with PSA nadir values exceeding 0.5 ng/mL should be considered for inclusion in randomised trials investigating the use of drugs that have extended survival in castration-resistant metastatic prostate cancer.

IS A VISIBLE (HYPOECHOIC) LESION AT BIOPSY AN INDEPENDENT PREDICTOR OF PROSTATE CANCER OUTCOME?

The aim of this study was to evaluate the prognostic implications of the sonographic appearance of prostate cancers. All patients with biopsy-proven prostate cancer between January 2003 and July 2004 (and at least 5 years of follow-up) were selected retrospectively. After exclusions, 101 patients constituted our study population and were divided into isoechoic (or nonvisible) and hypoechoic (or visible) lesion. The clinical outcomes of these two groups were compared. The outcomes for the two groups were significantly different (p < 0.01). For nonvisible lesions, 37 of the 41 patients (90.2%) had no disease relapse and 2 (4.9%) had biochemical failure. For the visible lesions, 37 of the 60 (61.6%) patients were free of recurrence, 7 (11.7%) had systemic metastases and 10 (16.7%) died of complications related to prostate cancer. Our data show that patients with nonvisible prostate cancer had significantly better outcomes than patients with visible lesions during a five-year period of evaluation. (E-mail: fmuglia@fmrp.usp.br) (c) 2012 World Federation for Ultrasound in Medicine & Biology.

Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

Background: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). Methods: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. Results: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). Conclusion: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.

The negative binomial-beta Weibull regression model to predict the cure of prostate cancer

In this article, for the first time, we propose the negative binomial-beta Weibull (BW) regression model for studying the recurrence of prostate cancer and to predict the cure fraction for patients with clinically localized prostate cancer treated by open radical prostatectomy. The cure model considers that a fraction of the survivors are cured of the disease. The survival function for the population of patients can be modeled by a cure parametric model using the BW distribution. We derive an explicit expansion for the moments of the recurrence time distribution for the uncured individuals. The proposed distribution can be used to model survival data when the hazard rate function is increasing, decreasing, unimodal and bathtub shaped. Another advantage is that the proposed model includes as special sub-models some of the well-known cure rate models discussed in the literature. We derive the appropriate matrices for assessing local influence on the parameter estimates under different perturbation schemes. We analyze a real data set for localized prostate cancer patients after open radical prostatectomy.

Biochemical control of prostate cancer with iodine-125 brachytherapy alone: experience from a single institution

Brachytherapy is an adequate option as monotherapy for localised prostate cancer. The objective of this study was to evaluate and compare biochemical failure free survival (BFFS) after low-dose-rate brachytherapy (LDRB) alone for patients with prostate cancer using ASTRO and Phoenix criteria, and detect prognostic factors. Data on 220 patients treated between 1998 and 2002 with LDRB were retrospectively analysed. Neoadjuvant hormone therapy was used in 74 (33.6%) patients. Median follow-up was 53.5 months (24-116). Five year BFFS was 83.0% and 83.7% using, respectively, the ASTRO and Phoenix criteria. Low -and intermediate-risk patients presented, respectively, 86.7% and 77.8% 5-year BFFS using the ASTRO definition (p=0.069), and 88.5% and 78.6% considering the Phoenix criteria (p=0.016). Bounce was observed in 66 (30%) patients. Multivariate analysis detected PSA at diagnosis < 10 ng/ml and less than 50% positive biopsy fragments as favourable prognostic factors, regarding BF using both criteria. For the Phoenix criteria, also Gleason score < 7 and low-risk group were identified as independent favourable prognostic factors. LDRB alone should be considered mostly for low-risk patients. PSA level was a strong independent prognostic factor. We support the use of the Phoenix criteria for detection of BF in patients submitted to LDRB alone.

Standard surgical treatment for benign prostatic hyperplasia is safe for patients over 75 years: Analysis of 100 cases from a high-volume urologic center

OBJECTIVES: In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center. METHODS: We analyzed 100 consecutive patients older than 75 years who had undergone transurethral prostatic resection of the prostate or open prostatectomy for treatment of benign prostatic hyperplasia from January 2008 to March 2010. We analyzed patient age, prostate volume, prostate-specific antigen level, international prostatic symptom score, quality of life score, urinary retention, co-morbidities, surgical technique and satisfaction with treatment. RESULTS: Median age was 79 years. Forty-eight patients had undergone transurethral prostatic resection of the prostate, and 52 had undergone open prostatectomy. The median International Prostatic Symptom Score was 20, the median prostate volume was 83 g, 51% were using an indwelling bladder catheter, and the median prostate-specific antigen level was 5.0 ng/ml. The most common comorbidities were hypertension, diabetes and coronary disease. After a median follow-up period of 17 months, most patients were satisfied. Complications were present in 20% of cases. The most common urological complication was urethral stenosis, followed by bladder neck sclerosis, urinary fistula, late macroscopic hematuria and persistent urinary incontinence. The most common clinical complication was myocardial infarction, followed by acute renal failure requiring dialysis. Incidental carcinoma of the prostate was present in 6% of cases. One case had urothelial bladder cancer. CONCLUSIONS: Standard surgical treatments for benign prostatic hyperplasia are safe and satisfactory among the elderly. Complications are infrequent, and urethral stenosis is the most common. No clinical variable is associated with the occurrence of complications.

Are we able to correctly identify prostate cancer patients who could be adequately treated by focal therapy?

Introduction and Objective: Because of the improvements on detection of early stage prostate cancer over the last decade, focal therapy for localized prostate cancer (PC) has been proposed for patients with low-risk disease. Such treatment would allow the control of cancer, thereby diminishing side effects, such as urinary incontinence and sexual dysfunction, which have an enormous impact on quality of life. The critical issue is whether it is possible to preoperatively predict clinically significant unifocal or unilateral prostate cancer with sufficient accuracy. Our aim is to determine whether there is any preoperative feature that can help select the ideal patient for focal therapy. Material and methods: A total of 599 patients who underwent transrectal ultrasound, (TRUS)-guided prostate biopsy followed by radical prostatectomy to treat PC were examined in our laboratory between 2001 and 2009. We established very restricted criteria to select patients with very-low-risk disease for whom focal therapy would be suitable (only I biopsy core positive, tumor no larger than 80% of a single core, no perineural invasion, PSA serum level < 10 ng/ml, Gleason score < 7 and clinical stage T1c, T2a-b). We defined 2 groups of patients who would be either adequately treated or not treated by focal therapy. The primary endpoint was the evaluation of preoperative features in order to identify which parameters should be considered when choosing good candidates for focal therapy. Results: Fifty-six out of 599 patients met our criteria. The mean age was 59 years, and the mean number of biopsy cores was 14.4. Forty-seven (83.9%) were staged T1c, and 9 (16.1%) were staged T2a-b. Forty-four (78.6%) patients could be considered to have been adequately treated by focal therapy, and 12 (21.4%) could not. There was no statistical difference between the 2 groups considering age, clinical stage, PSA levels, Gleason score, and tumor volume in the biopsy. All 12 patients who could be considered inadequately treated had a bilateral, significant secondary tumor, 58.3% had Gleason >= 7, and 25% were staged pT3. Conclusion: Although focal therapy might be a good option for patients with localized prostate cancer, we are so far unable to select which of them would benefit from it based on preoperative data, even using very restricted criteria, and a considerable proportion of men would still be left undertreated. (c) 2012 Elsevier Inc. All rights reserved.

Fitas adesivas, “Vanish” e técnica clareadora caseira: aspectos importantes a serem considerados

Em trabalhos experimentais, o peróxido de hidrogênio revelou-se um promotor da carcinogênese química bucal e em outras mucosas gastrintestinais. O peróxido de hidrogênio representa um cocarcinógeno, pois não inicia sozinho uma neoplasia maligna epitelial, mas pode potencializar outros agentes iniciadores. Na boca, onde atuam vários carcinógenos, a mucosa está, em sua maior parte, desprotegida, pois não tem em sua superfície uma espessa e contínua camada de queratina, como a pele. Em qualquer forma de ação, o peróxido de hidrogênio - o único clareador de dentes - requer técnica que proteja a mucosa e a região cervical do esmalte na junção com o cemento, e dificulte que seja engolido, indo para as partes mais inferiores do trato gastrintestinal. Este trabalho centra-se principalmente na necessidade de convencer pacientes, profissionais e agentes do mercado de que a forma mais correta e segura de clarear dentes está no consultório dos profissionais treinados e conscientes.

Quantification of fractal dimension and Shannon’s entropy in histological diagnosis of prostate cancer

Background: Prostate cancer is a serious public health problem that affects quality of life and has a significant mortality rate. The aim of the present study was to quantify the fractal dimension and Shannon’s entropy in the histological diagnosis of prostate cancer. Methods: Thirty-four patients with prostate cancer aged 50 to 75 years having been submitted to radical prostatectomy participated in the study. Histological slides of normal (N), hyperplastic (H) and tumor (T) areas of the prostate were digitally photographed with three different magnifications (40x, 100x and 400x) and analyzed. The fractal dimension (FD), Shannon’s entropy (SE) and number of cell nuclei (NCN) in these areas were compared. Results: FD analysis demonstrated the following significant differences between groups: T vs. N and H vs. N groups (p < 0.05) at a magnification of 40x; T vs. N (p < 0.01) at 100x and H vs. N (p < 0.01) at 400x. SE analysis revealed the following significant differences groups: T vs. H and T vs. N (p < 0.05) at 100x; and T vs. H and T vs. N (p < 0.001) at 400x. NCN analysis demonstrated the following significant differences between groups: T vs. H and T vs. N (p < 0.05) at 40x; T vs. H and T vs. N (p < 0.0001) at 100x; and T vs. H and T vs. N (p < 0.01) at 400x. Conclusions: The quantification of the FD and SE, together with the number of cell nuclei, has potential clinical applications in the histological diagnosis of prostate cancer.

Standard surgical treatment for benign prostatic hyperplasia is safe for patients over 75 years: analysis of 100 cases from a high-volume urologic center

OBJECTIVES: In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center. METHODS: We analyzed 100 consecutive patients older than 75 years who had undergone transurethral prostatic resection of the prostate or open prostatectomy for treatment of benign prostatic hyperplasia from January 2008 to March 2010. We analyzed patient age, prostate volume, prostate-specific antigen level, international prostatic symptom score, quality of life score, urinary retention, co-morbidities, surgical technique and satisfaction with treatment. RESULTS: Median age was 79 years. Forty-eight patients had undergone transurethral prostatic resection of the prostate, and 52 had undergone open prostatectomy. The median International Prostatic Symptom Score was 20, the median prostate volume was 83 g, 51% were using an indwelling bladder catheter, and the median prostatespecific antigen level was 5.0 ng/ml. The most common comorbidities were hypertension, diabetes and coronary disease. After a median follow-up period of 17 months, most patients were satisfied. Complications were present in 20% of cases. The most common urological complication was urethral stenosis, followed by bladder neck sclerosis, urinary fistula, late macroscopic hematuria and persistent urinary incontinence. The most common clinical complication was myocardial infarction, followed by acute renal failure requiring dialysis. Incidental carcinoma of the prostate was present in 6% of cases. One case had urothelial bladder cancer. CONCLUSIONS: Standard surgical treatments for benign prostatic hyperplasia are safe and satisfactory among the elderly. Complications are infrequent, and urethral stenosis is the most common. No clinical variable is associated with the occurrence of complications.

The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer

Choline positron emission tomography (PET)/computed tomography (CT) is a currently used diagnostic tool in restaging prostate cancer (PCa) patients with increasing prostate-specific antigen (PSA) after either radical prostatectomy (RP) or external-beam radiation therapy (EBRT). However, no final recommendations have been made on the use of this modality for patient management.