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Gleason Grade (gleason + grade)
Selected AbstractsEvaluation of molecular forms of prostate-specific antigen and human kallikrein 2 in predicting biochemical failure after radical prostatectomyINTERNATIONAL JOURNAL OF CANCER, Issue 3 2009Sven Wenske Abstract Most pretreatment risk-assessment models to predict biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer rely on total prostate-specific antigen (PSA), clinical stage, and biopsy Gleason grade. We investigated whether free PSA (fPSA) and human glandular kallikrein-2 (hK2) would enhance the predictive accuracy of this standard model. Preoperative serum samples and complete clinical data were available for 1,356 patients who underwent RP for localized prostate cancer from 1993 to 2005. A case-control design was used, and conditional logistic regression models were used to evaluate the association between preoperative predictors and BCR after RP. We constructed multivariable models with fPSA and hK2 as additional preoperative predictors to the base model. Predictive accuracy was assessed with the area under the ROC curve (AUC). There were 146 BCR cases; the median follow up for patients without BCR was 3.2 years. Overall, 436 controls were matched to 146 BCR cases. The AUC of the base model was 0.786 in the entire cohort; adding fPSA and hK2 to this model enhanced the AUC to 0.798 (p = 0.053), an effect largely driven by fPSA. In the subgroup of men with total PSA ,10 ng/ml (48% of cases), adding fPSA and hK2 enhanced the AUC of the base model to a similar degree (from 0.720 to 0.726, p = 0.2). fPSA is routinely measured during prostate cancer detection. We suggest that the role of fPSA in aiding preoperative prediction should be investigated in further cohorts. © 2008 Wiley-Liss, Inc. [source] How much does Gleason grade of follow-up biopsy differ from that of initial biopsy in untreated, Gleason score 4,7, clinically localized prostate cancer?THE PROSTATE, Issue 15 2007R. Choo Abstract OBJECTIVE To compare histologic grades between an initial biopsy and a follow-up biopsy in untreated, Gleason score (GS) 4,7, clinically localized prostate cancer. METHODS AND MATERIALS In a prospective single-arm cohort study, clinically localized, GS 4,7, prostate cancer was managed with active surveillance alone, provided that a pre-defined definition of disease progression was not met. One hundred five (63%) of a total of 168 eligible patients underwent a follow-up prostate biopsy during surveillance. Median time to a follow-up biopsy was 22 months (range: 7,81). Histologic grades between these two biopsies were compared to evaluate the extent of histologic grade change. RESULTS On the follow-up biopsy, GS was unchanged in 33 patients (31%), upgraded in 37 (35%), and downgraded in 34 (32%). Eleven (10%) had upgrading by 2 Gleason points or more. Eight (8%) had upgrading to GS 8 (none to GS 9 or 10); of these, six were among those with upgrading by 2 Gleason points or more. Twenty-seven (26%) had no malignancy on the follow-up biopsy. Negative follow-up biopsy was more prevalent in patients with a small volume of malignancy in the initial biopsy and a low baseline PSA. CONCLUSIONS No consistent change in histologic grade was observed on the follow-up biopsy at a median of 22 months in untreated, GS 4,7, clinically localized prostate cancer. Upgrading to GS ,8 or by 2 Gleason points or more was relatively uncommon. Prostate 67: 1614,1620, 2007. © 2007 Wiley-Liss, Inc. [source] Stat3 activation in prostatic carcinomasTHE PROSTATE, Issue 4 2002Rajiv Dhir Abstract BACKGROUND Activated Stat3 is found in various types of immortal cell lines and cancers. We and others have previously demonstrated that Stat3 is constitutively activated in rat and human prostate cancer cell lines, and that Stat3 activation is involved in IL-6-mediated signaling transduction in prostate cancer cells. The aim of this study is to examine quantitative Stat3 activity in benign and malignant human prostate tissues and analyze the association between Stat3 activity levels and the clinical and pathologic parameters. METHODS Stat3 activity levels were analyzed in a total of 104 human primary prostate tissues using electromobility shift assay and immunohistochemical staining for phosphorylated Stat3. The tissue samples used were 42 prostate carcinomas, 42 matched normal prostate tissues from patients with prostatic adenocarcinoma (normal adjacent to tumor), and 20 normal prostate tissues from organ donors. RESULTS Significantly higher levels of constitutive Stat3 activity were detected in both prostate carcinomas and the matched normal prostate tissues adjacent to tumors compared to the normal prostates from donors without prostate cancer. There was no significant difference of Stat3 activity in foci of tumor and normal prostate tissue adjacent to tumor. No correlation was seen between Stat3 activity and Gleason grade or serum PSA levels in samples from prostate carcinomas. CONCLUSIONS These results indicate that Stat3 is constitutively activated in prostate cancer. The high level of Stat3 activity in both the prostate carcinomas and the normal prostate tissues adjacent to tumors suggests that Stat3 activation may occur before detectable histological alterations of the prostate. Prostate 51: 241,246, 2002. © 2002 Wiley-Liss, Inc. [source] A pretreatment nomogram predicting biochemical failure after salvage cryotherapy for locally recurrent prostate cancerBJU INTERNATIONAL, Issue 2 2010Philippe E. Spiess Study Type , Prognosis (retrospective cohort) Level of Evidence 2b OBJECTIVE To gather a pooled database from six tertiary-care referral centres using salvage cryotherapy (SC) for locally recurrent prostate cancer, and develop a pretreatment nomogram allowing a prediction of the probability of biochemical failure after SC, based on pretreatment clinical variables. PATIENTS AND METHODS We retrospectively analysed 797 men treated at six tertiary-care referral centres with SC for locally recurrent disease after primary radiotherapy with curative intent. The median duration of follow-up from the time of SC to the date of last contact was 3.4 years. The primary study endpoint was biochemical failure, defined as a serum prostate-specific antigen (PSA) level after SC of >0.5 ng/mL. RESULTS Overall, the rate of biochemical failure was 66% with a median of 3.4 years of follow-up. A logistic regression model was used to predict biochemical failure. Covariates included serum PSA level at diagnosis, initial clinical T stage, and initial biopsy Gleason score. On the basis of these results, a pretreatment nomogram was developed which can be used to help select patients best suited for SC. Our pretreatment nomogram was internally validated using 500 bootstrap samples, with the concordance index of the model being 0.70. CONCLUSION A pretreatment nomogram based on several diagnostic variables (serum PSA level at diagnosis, biopsy Gleason grade, and initial clinical T stage) was developed and might allow the selection of ideal candidates for SC. [source] The independent value of tumour volume in a contemporary cohort of men treated with radical prostatectomy for clinically localized diseaseBJU INTERNATIONAL, Issue 4 2010Sima P. Porten Study Type , Prognosis (case series) Level of Evidence 4 OBJECTIVE To determine if prostate tumour volume is an independent prognostic factor in a contemporary cohort of men who had a radical prostatectomy (RP) for clinically localized disease, as the effect of tumour volume on prostate cancer outcomes has not been consistently shown in the era of widespread screening with prostate-specific antigen (PSA). PATIENTS AND METHODS The study included 856 men who had RP from 1998 to 2007 for localized prostate cancer. Tumour volume based on pathology was analysed as a continuous and categorized (<0.26, 0.26,0.50, 0.51,1.00, 1.01,2.00, 2.01,4.00, >4.00 mL) variable using Cox proportional hazards regression and Kaplan-Meier analysis. A multivariable analysis was also conducted controlling for PSA level, Gleason grade, surgical margins, and pathological stage. RESULTS Tumour volume had a positive association with grade and stage, but did not correlate with biochemical recurrence-free survival on univariate analysis as a continuous variable (hazard ratio 1.00, P = 0.09), and was only statistically significant for volumes of >4 mL as a categorical variable. No tumour volume was an independent predictor of prostate cancer recurrence on multivariate analysis. There was no difference between tumour volume and time to cancer recurrence for organ-confined tumours using Kaplan-Meier analysis. In low-risk patients (PSA level <10 ng/mL, Gleason score ,6, clinical stage T1c/T2a) tumour volume did not correlate with biochemical recurrence-free survival in univariate or multivariable analysis. CONCLUSIONS There is no evidence that tumour volume is an independent predictor of prostate cancer outcome and it should not be considered as a marker of tumour risk, behaviour or prognosis. [source] Urinary incontinence after radical retropubic prostatectomy: the outcome of a surgical techniqueBJU INTERNATIONAL, Issue 4 2003A. Moinzadeh It is a reflection of the many manuscripts submitted on urological oncology in general, and prostate cancer in particular, that I am publishing 10 papers in this section this month. Seven of these relate to the latter subject. The authors from the Lahey Clinic describe their technique of radial prostatectomy and include a novel method of posterior bladder plication. They report an early return to continence and conclude that the technique is important in achieving their excellent results. In another study the group from Stockport show that patients often make decisions about types of treatment for prostate cancer having been strongly influenced by their partner, who in turn may have had pre-existing conceptions about this. They recommend early involvement of the partner to help in this very important decision-making. The two papers on bladder cancer describe possible prognostic factors, both clinical and laboratory-based, from a large experience in Hamburg and Mansoura. OBJECTIVE To analyse the incidence of incontinence after radical retropubic prostatectomy (RRP) and the time to return of continence, using an RRP technique including a novel posterior bladder plication PATIENTS AND METHODS We retrospectively reviewed the medical records of 200 consecutive patients who underwent RRP between September 1995 and February 1997, by one surgeon, at our institution. Patient characteristics including age, preoperative prostate-specific antigen (PSA) level and Gleason grade, were assessed. Continence was assessed before and after RRP by either a third-party patient interview or a prospective validated questionnaire. Continence was defined as not requiring the use of any sanitary pads or diapers. The continence rate was determined immediately after catheter removal, and at 3, 6, 12 and 15 months after RRP. RESULTS The mean age of the patients was 59.4 years, the preoperative PSA level 8.5 ng/mL and the Gleason grade 6.1. The time to continence and percentage of continent patients was 63.5% immediately, 82% at 3 months, 91% at 6 months, and 98.5% at 12 months after RRP. At 15 months, 199 of 200 consecutive patients were continent (99.5%). CONCLUSION With our technique there was an early return to continence and only a minor incontinence rate at 15 months. The cumulative effect of sequential technical manoeuvres in our RRP technique, including posterior bladder plication, is critical for continence after RRP. [source] Evaluation of HER-2/neu expression in prostatic adenocarcinomaCANCER, Issue 8 2002A request for a standardized, organ specific methodology Abstract BACKGROUND Some evidence suggests a role for HER-2/neu overexpression in prostate carcinoma progression. Reported rates of HER-2/neu overexpression in patients with prostate carcinoma vary greatly. METHODS The authors studied radical prostatectomy specimens from 38 patients who had biochemical failure after undergoing radical prostatectomy for prostate carcinoma. Immunohistochemistry for HER-2/neu overexpression using the HercepTest kit (Dako Corporation, Carpenteria, CA) was employed. Two different antigen-retrieval techniques were used: 1) the standard U.S. Food and Drug Administration (FDA)-approved HercepTest assay and 2) a modified HercepTest, which employed an alkaline citrate buffer, pH 9.0, for antigen retrieval and a 1-hour primary antibody incubation time. The level of HER-2/neu expression was evaluated on a scale from 0 (no staining) to 3+ according to the published guidelines. Fluorescent in situ hybridization for gene amplification was performed on all specimens. RESULTS With the standard technique, only one specimen had 2+ staining, and no specimens had 3+ staining. With the modified technique, 10 specimens (26%) had 2+ staining, and 9 specimens (24%) had 3+ staining. There was a significant association between the level of HER-2/neu expression shown with the modified technique and tumor stage (P = 0.03) as well as Gleason grade (P = 0.01). None of the specimens had HER-2/neu gene amplification. CONCLUSIONS The authors report a simple modification of the HercepTest that resulted in an increased rate of HER-2/neu expression, which was correlated with poor-risk pathologic findings. The findings suggest that adenocarcinoma of the prostate should be evaluated for HER-2/neu expression with a prostate specific immunohistochemical procedure that differs from the FDA-approved standard procedure. Cancer 2002;95:1650,5. © 2002 American Cancer Society. DOI 10.1002/cncr.10839 [source] A comprehensive and novel predictive modeling technique using detailed pathology factors in men with localized prostate carcinomaCANCER, Issue 7 2002Louis Potters M.D. Abstract BACKGROUND The purpose of the current study was to evaluate modeling strategies using sextant core prostate biopsy specimen data that would best predict biochemical control in patients with localized prostate carcinoma treated with permanent prostate brachytherapy (PPB). METHODS One thousand four hundred seventy,seven patients underwent PPB between 1992 and 2000. The authors restricted analysis to those patients who had sextant biopsies (n = 1073). A central pathology review was undertaken on all specimens. Treatment consisted of PPB with either I-125 or Pd-103 prescribed to 144 Gy or 140 Gy, respectively. Two hundred twenty,eight patients (21%) received PPB in combination with external radiotherapy and 333 patients (31%) received neoadjuvant hormones. In addition to clinical stage, biopsy Gleason sum, and pretreatment prostate specific antigen (pretx-PSA), the following detailed biopsy variables were considered: mean percentage of cancer in an involved core; maximum percentage of cancer; mean primary and secondary Gleason grades; maximum Gleason grade (primary or secondary); percentage of cancer in the apex, mid, and base; percent of cores positive; maximum primary and secondary Gleason grades in apex, mid, and base; maximum percent cancer in apex, mid, and base; maximum Gleason grade in apex, mid, and base; maximum primary Gleason grade; and maximum secondary Gleason grade. In all, 23 biopsy variables were considered. Four modeling strategies were compared. As a base model, the authors considered the pretx-PSA, clinical stage, and biopsy Gleason sum as predictors. For the second model, the authors added percent of cores positive. The third modeling strategy was to use stepwise variable selection to select only those variables (from the total pool of 26) that were statistically significant. The fourth strategy was to apply principal components analysis, which has theoretical advantages over the other strategies. Principal components analysis creates component scores that account for maximum variance in the predictors. RESULTS The median followup of the study cohort was 36 months (range, 6,92), and the Kattan modification of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition was used to define PSA freedom from recurrence (PSA-FFR). The four models were compared in their ability to predict PSA-FFR as measured by the Somers D rank correlation coefficient. The Somers D rank correlation coefficients were then corrected for optimism with use of bootstrapping. The results for the four models were 0.32, 0.34, 0.37, and 0.39, respectively. CONCLUSIONS The current study shows that the use of principal components analysis with additional pathology data is a more discriminating model in predicting outcome in prostate carcinoma than other conventional methods and can also be used to model outcome predictions for patients treated with radical prostatectomy and external beam. Cancer 2002;95:1451,6. © 2002 American Cancer Society. DOI 10.1002/cncr.10869 [source] Immunohistochemical detection of cysteine-rich secretory protein 3 in tissue and in serum from men with cancer or benign enlargement of the prostate glandTHE PROSTATE, Issue 6 2006Anders Bjartell Abstract BACKGROUND Recently, the gene for cysteine-rich secretory protein 3 (CRISP-3) was reported to be highly upregulated in prostate cancer (PCa) compared to benign prostatic tissue. The current aims were to investigate diagnostic use of tissue expression and immunodetection in serum of CRISP-3 for detection or monitoring of PCa. METHODS Radical prostatectomy specimens and tissue microarrays from transurethral resections and metastases were analyzed for CRISP-3 and PSA by immunohistochemistry. CRISP-3 in tissue homogenates and in serum was measured by an in-house ELISA and PSA by a commercially available immunoassay. RESULTS Immunostaining for CRISP-3 in benign prostatic epithelium was generally weak or not detectable. Specific and strong immunostaining was found in a major proportion of cells in high-grade prostatic-intraepithelial-neoplasia (HG-PIN,12/17 patients), in most primary tumors (111/115), and in lymph node (11/15) and bone (12/15) metastases. CRISP-3 immunostaining intensity was regularly strong in areas of Gleason grades 4/5, where PSA-immunoreaction was less intense. Serum levels of CRISP-3 were not different in patients with PCa (n,=,152) compared to men with BPH (n,=,81). There was a very weak co-variation between levels of CRISP-3 versus PSA in serum from PCa patients (P,<,0.05). After orchiectomy, levels of CRISP-3 in serum decreased in median with 11% compared to a 97% median decrease of PSA in serum from 15/20 patients with advanced PCa. CONCLUSIONS Strong immunostaining for CRISP-3 is common in HG-PIN and preserved in most PCa specimens, which warrant further immunohistochemical studies of CRISP-3 in PCa. Serum levels of CRISP-3 do not primarily reflect PCa. Prostate 66:591,603, 2006. © 2005 Wiley-Liss, Inc. [source] Body mass index is weakly associated with, and not a helpful predictor of, disease progression in men with clinically localized prostate carcinoma treated with radical prostatectomyCANCER, Issue 10 2005Kozhaya N. Mallah M.D. Abstract BACKGROUND Several studies have recently suggested an association between body mass index (BMI) and disease progression after radical prostatectomy. In the current study, the authors examined this association and that between the reciprocal of BMI (INVBMI, 1/BMI) and progression-free probability in men treated with radical retropubic prostatectomy (RRP) for clinically localized prostate carcinoma. METHODS The authors retrospectively studied 2210 patients who underwent RRP at Memorial Sloan-Kettering Cancer Center between September 1986 and May 2003. Clinicopathologic variables analyzed included BMI (kg/m2), preoperative serum prostate-specific antigen level (ng/mL), clinical T classification, year of surgery, race, biopsy-derived primary and secondary Gleason grades, and INVBMI, known to better correlate with percent body fat than BMI. Cox regression analysis was used to examine the possible association between BMI or its reciprocal with disease progression after controlling for the effects of common prognostic factors. The areas under the receiver operating curve (AUC) for models with and without INVBMI were calculated RESULTS Of the 2210 patients analyzed, 251 experienced disease progression in a median follow-up time of 25.9 months (range, 0,143 months). After adjusting for all clinical variables, both BMI (P = 0.071; hazards ratio [HR] = 1.027) and INVBMI (P = 0.041; HR < 0.001) were associated with disease progression. However, the areas under AUC for models with and without INVBMI were similar (range, 0.794,0.798). CONCLUSIONS Although conflicting evidence has been reported regarding the link between obesity and an increased risk of developing prostate carcinoma, as well as an increased risk of developing aggressive disease and prostate carcinoma-related mortality, the authors found weak associations with disease progression for both BMI and INVBMI. These variables were of negligible prognostic value in men who received surgery. Studies with longer follow-up, that examine alternative end points, and that follow treatment(s) besides surgery are needed. Cancer 2005. © 2005 American Cancer Society. [source] A comprehensive and novel predictive modeling technique using detailed pathology factors in men with localized prostate carcinomaCANCER, Issue 7 2002Louis Potters M.D. Abstract BACKGROUND The purpose of the current study was to evaluate modeling strategies using sextant core prostate biopsy specimen data that would best predict biochemical control in patients with localized prostate carcinoma treated with permanent prostate brachytherapy (PPB). METHODS One thousand four hundred seventy,seven patients underwent PPB between 1992 and 2000. The authors restricted analysis to those patients who had sextant biopsies (n = 1073). A central pathology review was undertaken on all specimens. Treatment consisted of PPB with either I-125 or Pd-103 prescribed to 144 Gy or 140 Gy, respectively. Two hundred twenty,eight patients (21%) received PPB in combination with external radiotherapy and 333 patients (31%) received neoadjuvant hormones. In addition to clinical stage, biopsy Gleason sum, and pretreatment prostate specific antigen (pretx-PSA), the following detailed biopsy variables were considered: mean percentage of cancer in an involved core; maximum percentage of cancer; mean primary and secondary Gleason grades; maximum Gleason grade (primary or secondary); percentage of cancer in the apex, mid, and base; percent of cores positive; maximum primary and secondary Gleason grades in apex, mid, and base; maximum percent cancer in apex, mid, and base; maximum Gleason grade in apex, mid, and base; maximum primary Gleason grade; and maximum secondary Gleason grade. In all, 23 biopsy variables were considered. Four modeling strategies were compared. As a base model, the authors considered the pretx-PSA, clinical stage, and biopsy Gleason sum as predictors. For the second model, the authors added percent of cores positive. The third modeling strategy was to use stepwise variable selection to select only those variables (from the total pool of 26) that were statistically significant. The fourth strategy was to apply principal components analysis, which has theoretical advantages over the other strategies. Principal components analysis creates component scores that account for maximum variance in the predictors. RESULTS The median followup of the study cohort was 36 months (range, 6,92), and the Kattan modification of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition was used to define PSA freedom from recurrence (PSA-FFR). The four models were compared in their ability to predict PSA-FFR as measured by the Somers D rank correlation coefficient. The Somers D rank correlation coefficients were then corrected for optimism with use of bootstrapping. The results for the four models were 0.32, 0.34, 0.37, and 0.39, respectively. CONCLUSIONS The current study shows that the use of principal components analysis with additional pathology data is a more discriminating model in predicting outcome in prostate carcinoma than other conventional methods and can also be used to model outcome predictions for patients treated with radical prostatectomy and external beam. Cancer 2002;95:1451,6. © 2002 American Cancer Society. DOI 10.1002/cncr.10869 [source] |