Prostatectomy Gleason Score Research Articles

Cancer Care Ontario Guidelines for radical prostatectomy: striving for continuous quality improvement in community practice.

: Cancer Care Ontario has published an evidence-based guideline on their website "Guideline for Optimization of Surgical and Pathological Quality Performance for Radical Prostatectomy in Prostate Cancer Management: Surgical and Pathological Guidelines." The evidentiary base for this guideline was recently published in CUAJ. The CCO guideline proposes the following: a positive surgical margin (PSM) rate of <25% for organ-confined disease (pT2), a perioperative mortality of <1%, a rate of rectal injury <1%, and a blood transfusion rate <10% in non-anemic patients. The objective of this study was to review the radical prostatectomy practice at the Grey Bruce Health Services, an Ontario community hospital, and to compare our performance in relation to the Cancer Care Ontario guideline and the literature. : We conducted a retrospective review of all radical prostatectomies performed at the Grey Bruce Health Services from January 1, 2006 to December 31, 2007. The following data were obtained from clinical records and pathology reports: patient age, pre-biopsy prostate-specific antigen, biopsy Gleason score, resected prostate gland weight, radical prostatectomy Gleason score, surgical margin status, pathological tumour stage (pT), lymph node dissection status, perioperative incidence of transfusion of blood products and if the patient was anemic (hemoglobin <140 g/L) preoperatively, incidence of rectal injury, and perioperative mortality within 30 days following surgery. : Using the method proposed by D'Amico, most patients undergoing radical prostatectomy were intermediate risk (62%), with a minority of low-risk (24%) and high-risk (14%) patients. The overall PSM rate was 37%. The rate of PSMs in organ-confined disease (pT2) was 26%. There was a statistically significant trend between increasing D'Amico risk category and increasing rate of PSM (Cochran-Armitage trend test, p = 0.023). There was a strong correlation between the pathological tumour stage and the rate of PSM (Cochran-Armitage trend test, p = 0.0003). The rate of blood transfusion in non-anemic patients was 6%. There was 1 patient (0.8%) who experienced a rectal injury. There were no perioperative deaths in our study group. : Our results show that a community hospital group can appropriately select patients to undergo radical prostatectomy, as well as achieve an acceptable rate of PSMs. We believe that ongoing critical appraisal and reflective practice are essential to improving surgical outcomes and providing quality care.

Comparison of diffusion weighted imaging and transrectal ultrasound-guided biopsy in predicting aggressiveness of prostate cancer

Objective To retrospectively evaluate the utility of apparent diffusion coefficient (ADC) values in predicting aggressiveness of prostate cancer.Comparison was made with transrectal ultrasound-guided biopsy Gleason scores (GS) and prostatectomy GS.Methods Diffusion weighted images of 51 patients with biopsy-proven prostate cancer were obtained using 1.5 T MR with a pelvic phased-array coil.Regions of interest (ROIs) were drawn on areas of the suspicious lesion and the ADC values were calculated.The correlations between the ADC values and prostatectomy GS were assessed with Pearson correlation.The relationship between biopsy GS and prostatectomy GS were also evaluated.Meanwhile,receiver operating characteristic (ROC) curves were used to determine the ability of ADC values and biopsy GS in differentiating low-grade prostate cancer from intermediate/high grade prostate cancer.Results The accuracy of transrectal ultrasound-guided biopsy in predicting prostatectomy GS was 41.2％(21/51).Compared with prostatectomy GS,up to 11.8％ of the patients (n =6) was overestimated by biopsy,while 47.0％ (n =24) were underestimated.These 51 patients had a mean ADC value of (0.974 ±0.194) × 10-3 mm2/s.The mean ADC value of intermediate/high-grade tumors (n =35) was (0.907 ±0.160) ×10-3 mm2/s while that of low-grade tumors was (1.121 ±0.185) × 10-3 mm2/s (n =16).A significant negative correlation was found between mean ADC values of suspicious lesions and their prostatectomy GS (r =-0.761,P ＜ 0.01).No significant correlation was found between biopsy GS and prostatectomy GS (r =0.187,P =0.189).The area under the ROC curves of ADC and biopsy GS was 0.827 and 0.689,respectively.Conclusion The ADC values of cancerous areas in prostate perform better than biopsy GS in predicting aggressiveness of prostate cancer. Key words: Prostatic neoplasms; Magnetic resonance imaging; Comparative study

Prostate Total Tumor Extent Versus Index Tumor Extent—Which is Predictive of Biochemical Recurrence Following Radical Prostatectomy?

It is controversial whether tumor extent in radical prostatectomies predicts biochemical recurrence following surgery. We compared the predictive value of total tumor extent vs dominant nodule (index tumor) extent. A mean of 32 paraffin blocks was processed from prostate surgical specimens step sectioned at 3 to 5 mm intervals from 300 patients treated with radical retropubic prostatectomy. Each transverse section was subdivided into 2 anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a semiquantitative point count method. Dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer in the quadrants. Time to biochemical recurrence was analyzed by Kaplan-Meier product limit analysis. Prediction of shorter time to biochemical recurrence was determined by univariate and multivariate Cox proportional hazards models. Except for age and race, total and index tumor extent was significantly associated with higher preoperative prostate specific antigen, clinical stage T2, pathological stage greater than T2, positive surgical margins and higher radical prostatectomy Gleason score. Total and index tumor extent was significantly associated with time to biochemical recurrence in Kaplan-Meier estimates. Total and index tumor extent significantly predicted shorter time to biochemical recurrence on univariate analysis but only index tumor extent was an independent predictor of time to biochemical recurrence on multivariate analysis. The study indicates that any tumor extent estimate in surgical specimens should be related to the dominant nodule (index tumor) and not to total tumor extent.

Role of Stereotactic Body Radiation Therapy in Oligometastatic, Hormone Refractory Prostate Cancer

2011 and had a preoperative 3T multiparametric erMRI comprised the study cohort. We performed multivariable logistic regression analyses in all men and the 100 with favorable-risk PC to analyze whether erMRI evidence of T3 disease was associated with prostatectomy T3 or Gleason score (GS) 8-10 (in patients with biopsy GS 7) PC, adjusting for age, PSA level, clinical T-category, biopsy GS, and percent positive biopsies. Results: The accuracy of erMRI for extracapsular extension and seminal vesicle invasion was 75% and 95%, respectively. For all men, erMRI evidence of a T3 lesion vs. T2 was associated with increased odds of pT3 disease (adjusted odds ratio (AOR) 4.81, 95% confidence interval (CI) (1.36, 16.98), p Z 0.015) and pGS 8-10 (AOR 5.56, CI (1.10, 28.18), p Z 0.038). In men with favorable-risk disease, these results (Table) were AOR 4.14, CI (1.03, 16.56), p Z 0.045 and AOR 7.71, CI (1.36, 43.62), p Z 0.021, respectively. Conclusion: Three-T multiparametric erMRI in men with favorable-risk PC provides information beyond that contained in known preoperative predictors about the presence of occult extraprostatic and/or high-grade PC which can be used to counsel men who plan to undergo RP or radiation therapy (RT) about the possible need for adjuvant RT or the clinical utility of adding hormone therapy, respectively. Author Disclosure: J. Hegde: None. M. Chen: None. R.V. Mulkern: None. F.M. Fennessy: None. C.M. Tempany: None. A.V. D’Amico: None.

Pathological Features of Lymph Node Metastasis for Predicting Biochemical Recurrence After Radical Prostatectomy for Prostate Cancer

Subclassification of nodal stage may have prognostic value in men with lymph node metastasis at radical prostatectomy. We explored the role of extranodal extension, size of the largest metastatic lymph node and the largest metastasis, and lymph node density as predictors of biochemical recurrence. We reviewed pathological material from 261 patients with node positive prostate cancer. We examined the predictive value when adding the additional pathology findings to a base model including extraprostatic extension, seminal vesicle invasion, radical prostatectomy Gleason score, prostate specific antigen and number of positive lymph nodes using the Cox proportional hazards regression and Harrell concordance index. The median number of lymph nodes removed was 14 (IQR 9, 20) and the median number of positive lymph nodes was 1 (IQR 1, 2). At a median followup of 4.6 years (IQR 3.2, 6.0) 155 of 261 patients experienced biochemical recurrence. The mean 5-year biochemical recurrence-free survival rate was 39% (95% CI 33-46). Median diameter of the largest metastatic lymph node was 9 mm (IQR 5, 16). On Cox regression radical prostatectomy specimen Gleason score (greater than 7 vs 7 or less), number of positive lymph nodes (3 or greater vs 1 or 2), seminal vesicle invasion and prostate specific antigen were associated with significantly increased risks of biochemical recurrence. On subset analysis metastasis size significantly improved model discrimination (base model Harrell concordance index 0.700 vs 0.655, p = 0.032). Our study confirms that the number of positive lymph nodes is a predictor of biochemical recurrence in men with node positive disease. The improvement in prognostic value of measuring the metastatic focus warrants further investigation.

The Number of Cores Taken in Patients Diagnosed with a Single Microfocus at Initial Biopsy is a Major Predictor of Insignificant Prostate Cancer

Patients with a single microfocus of prostate cancer at initial biopsy represent the ideal candidates for active surveillance. We investigate whether the number of cores taken affects the concordance rate between microfocus of prostate cancer and the confirmation of a pathologically insignificant prostate cancer at radical prostatectomy. Data were analyzed from 233 patients with a single microfocus of prostate cancer at initial transrectal prostate biopsy (a single focus of Gleason 6 involving 5% or less of the core) subsequently treated with radical prostatectomy. The chi-square test, cubic spline analyses and logistic regression analyses were used to depict the relationship between the number of cores taken and the probability of confirming the presence of an indolent disease (pathologically confirmed insignificant prostate cancer defined as radical prostatectomy Gleason score 6 or less, tumor volume 0.5 ml or less and organ confined disease). Overall 65 patients (27.9%) showed pathologically confirmed insignificant prostate cancer at radical prostatectomy. The rate of pathologically confirmed insignificant prostate cancer was 3.8%, 29.6% and 39.4% in patients who underwent biopsy of 12 or fewer cores, 13 to 18 cores and 19 or more cores, respectively (p <0.001). After adjusting for the available confounders, age (p = 0.04), number of cores taken (p <0.001) and prostate specific antigen density (p <0.02) were independent predictors of pathologically confirmed insignificant prostate cancer. Of patients diagnosed with a single microfocus of prostate cancer the number of biopsy cores taken was a major independent predictor of having pathologically confirmed insignificant prostate cancer at radical prostatectomy. Therefore, when active surveillance is considered as a possible alternative in patients with microfocus of prostate cancer, the number of cores taken should be taken into account in decision making.

Pathological Characteristics of Prostate Cancer Recurrence After Radiation Therapy: Implications for Focal Salvage Therapy

Focal therapy is currently under investigation as an alternative to salvage radical prostatectomy for locally recurrent prostate cancer after primary radiation therapy. If patients can be selected properly, focal therapy could enable tumor eradication without the morbidity associated with salvage radical prostatectomy. We describe the pathological features of recurrent prostate cancer in salvage radical prostatectomy specimens and the implications of these results for focal therapy. We gathered data on 50 consecutive patients who had recurrence after primary radiation therapy and underwent salvage radical prostatectomy between 1993 and 2008. Preoperatively prostate specific antigen was less than 10 ng/ml in 49 patients (98%) and biopsy Gleason score was 7 or less in 18 (36%). Salvage radical prostatectomy specimens were analyzed for tumor zonal origin, site and volume, Gleason score and pathological stage. Median preoperative prostate specific antigen was 3.4 ng/ml. Pathological stage was T2 in 23 patients (46%). The salvage radical prostatectomy Gleason score was 7 or less in 17 patients (34%) and surgical margins were negative in 43 (86%). A single cancer focus was found in 33 cases (66%) while there was bilateral involvement in 37 (74%). The base and apex were involved in 23 cases (46%) and 37 tumors (74%) were located within 5.0 mm of the urethra. Median tumor volume was 1.27 cm(3) (range 0.05 to 12.96). Prostate cancer recurrence after radiation therapy is often bilateral and involves multiple zones. It is often high grade, bulky and close to the urethra. These findings suggest that planning salvage focal therapy after radiation failure will be difficult.

506 EFFECT OF ADVANCED AGE (≥70 YRS) ON PROSTATE CANCER CHARACTERISTICS, SURVIVAL AND POSTOPERATIVE CONTINENCE IN PATIENTS UNDERGOING RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized II1 Apr 2012506 EFFECT OF ADVANCED AGE (≥70 YRS) ON PROSTATE CANCER CHARACTERISTICS, SURVIVAL AND POSTOPERATIVE CONTINENCE IN PATIENTS UNDERGOING RADICAL PROSTATECTOMY Inga Kunz, Ulla Roggenbuck, Virgilijus Klevecka, Michael Musch, and Darko Kroepfl Inga KunzInga Kunz Essen, Germany More articles by this author , Ulla RoggenbuckUlla Roggenbuck Essen, Germany More articles by this author , Virgilijus KleveckaVirgilijus Klevecka Essen, Germany More articles by this author , Michael MuschMichael Musch Essen, Germany More articles by this author , and Darko KroepflDarko Kroepfl Essen, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.577AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In elderly prostate cancer (PCA) patients conservative treatment is frequently advocated due to a presumed short life expectancy. However, in Germany men aged 70 and 80 yrs still have an average life expectancy of 13 and 8 yrs, respectively. We examined the effect of advanced age on PCA characteristics and outcome after radical prostatectomy (RP). METHODS Of 1636 patients who underwent RP between 06/97 and 09/09 1225 were <70 yrs (group PAT<70) and 411 were >70 yrs (group PAT>70). Both groups were compared for PCA characteristics, postoperative continence, and overall (OS) and cancer-specific survival (CSS). Multivariate analyses were conducted to estimate the effect of advanced age on OS, CSS and postoperative continence. RESULTS The median ages of PAT>70 and PAT<70 were 72 yrs (range 70-85) and 64 yrs (range 40-69) (p<0.0001), respectively. PAT>70 were assigned higher ASA classes (ASA 3 19.5 vs. 11.3%; p<0.0001) and presented more cT2c-3 tumors (21.8 vs. 16.2%; p=0.0301), biopsy Gleason scores 8-10 (13.4 vs. 8.3%; p=0.0020), pT3a-4a tumors (55.2 vs. 47.8%; p=0.0096) and prostatectomy Gleason scores 7 (37.8 vs. 31.8%) and 8-10 (16.4 vs. 12.8%) (p=0.0040). Accordingly, PAT>70 presented a higher proportion of high risk PCA (24.3 vs. 20.6%; p=0.0600). No differences were observed concerning preoperative PSA (8.2 vs. 8.0 ng/mL; p=0.8980), rate of pelvic lymph node dissection (94.7 vs. 95.0%; p=0.2313), pN+ (11.9 vs. 10.8%; p=0.5248) and R+ status (32.1 vs. 33.6%; p=0.5904). The Kaplan-Meier curves showed a significantly lower 10-year OS (67% vs. 82%; p=0.01) and a trend towards a lower 10-year CSS (70% vs. 83%; p=0.06) in PAT>70. However, on multivariate analysis advanced age was not an independent predictor of OS (p=0.1020) and CSS (p=0.1949), whereas pN+ status (p<0.0001), prostatectomy Gleason scores 8-10 (p=0.0009 and p<0.0001, respectively) and ASA class 3 (p=0.0369 and p=0.0279, respectively) were. Two-year postoperative continence was comparable (ICSmaleSF incontinence symptom score 2.10 vs. 2.01; p=0.9843). In multivariate analysis it depended only on the preoperative ICSmaleSF incontinence symptom score (p<0.0001) but not on advanced age (p=0.3410). CONCLUSIONS Advanced age was not an independent predictor of postoperative continence or survival after RP. Rather, survival was associated with adverse PCA features and severe comorbidities. Consequently, it seems unjustifiable to generally exclude elderly patients from RP. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e208 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Inga Kunz Essen, Germany More articles by this author Ulla Roggenbuck Essen, Germany More articles by this author Virgilijus Klevecka Essen, Germany More articles by this author Michael Musch Essen, Germany More articles by this author Darko Kroepfl Essen, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

325 DIFFERENCES IN TMPRSS2-ERG GENE FUSION AND SPINK1 OVEREXPRESSION IN PROSTATE CANCER IN AFRICAN-AMERICAN AND CAUCASIAN MEN

INTRODUCTION AND OBJECTIVES: Prostate cancer is known to exhibit differences among racial/ethnic groups, with AfricanAmericans (AA) having a higher incidence and mortality from the disease than Caucasians. TMPRSS2-ERG gene fusions, which are present in approximately 50% of prostate cancers overall, have not been studied in large cohorts of AA patients. Similarly, while overexpression of SPINK1 has been associated with more aggressive forms of prostate cancer, differential expression in patients of different ethnicities has yet to be characterized. METHODS: A tissue microarray (TMA) was constructed containing tumor samples from 105 AA men who underwent radical prostatectomy (RP) at our institution. The control group was derived from a cohort of 112 prostate cancers from Caucasian men treated by RP at the same institution. SPINK1 overexpression was evaluated by IHC using a monoclonal antibody (Abnova, clone 4D4). Any positive staining by tumor was considered overexpressed. TMPRSS2-ERG gene fusions were evaluated by both IHC and FISH using a monoclonal ERG antibody and break-apart probes, respectively. Comparison of these two molecular abnormalities between the two groups was made using Fisher’s Exact test. RESULTS: TMPRSS2-ERG gene fusions were identified in 48/112 tumors (42.9%) in the control group of Caucasian men. In the AA cohort, however, TMPRSS2-ERG gene fusions were found in 28/105 tumors (26.7%; p 0.015). There was no significant difference in the mechanism of gene fusion between the two cohorts (translocation vs. translocation with deletion; p 1). Interestingly, SPINK1 overexpression was present in 24/105 tumors (22.9%) from AA patients in contrast to 11/106 tumors (10.4%) from Caucasian patients (p 0.017). ERG gene fusion and SPINK1 overexpression were mutually exclusive in all cases. Neither SPINK1 overexpression nor ERG gene fusion was associated with BCR with a median follow-up of 45 months (range: 7-128 months). There were no differences between the cohorts with respect to age, BMI, pre-operative PSA, biopsy Gleason score (GS), prostatectomy GS, clinical stage, pathologic stage, tumor volume, margin status, or biochemical recurrence (BCR). CONCLUSIONS: Our findings suggest possible pathobiologic differences between prostate cancers from AA and Caucasian men, with TMPRSS2-ERG gene fusions playing a lesser role and SPINK1 overexpression a larger role in AA as compared to Caucasian men. Further studies are needed to determine if these molecular differences explain, in part, differences in incidence and mortality between these two racial groups.

1339 LIMITED PELVIC LYMPHADENECTOMY IS NOT SUFFICIENT FOR STAGING IN HIGH RISK PROSTATE CANCER PATIENTS

You have accessJournal of UrologyProstate Cancer: Localized VI1 Apr 20121339 LIMITED PELVIC LYMPHADENECTOMY IS NOT SUFFICIENT FOR STAGING IN HIGH RISK PROSTATE CANCER PATIENTS Senji Hoshi, Natuho Hayashi, Yuuta Kurota, Kiyotugu Hoshi, Akinori Muto, Kenji Numahata, and Osamu Sugano Senji HoshiSenji Hoshi Yamagata, Japan More articles by this author , Natuho HayashiNatuho Hayashi Yamagata, Japan More articles by this author , Yuuta KurotaYuuta Kurota Yamagata, Japan More articles by this author , Kiyotugu HoshiKiyotugu Hoshi Yamagata, Japan More articles by this author , Akinori MutoAkinori Muto Yamagata, Japan More articles by this author , Kenji NumahataKenji Numahata Yamagata, Japan More articles by this author , and Osamu SuganoOsamu Sugano Yamagata, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1721AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Lymphadenectomy for prostate cancer is limited to obturator lymph nodes, although the internal and external lymph nodes represent the primary landing zone of lymphatic drainage. We performed anatomically adequate extended pelvic lymphadenectomy to assess the incidence of lymph node metastasis in cases of clinically localized prostate cancer. METHODS A total of 124 consecutive patients underwent extended pelvic lymphadenectomy at radical retropubic prostatectomy comprising 8 selective fields, namely the external iliac, internal iliac, obturator and common iliac lymph nodes bilaterally. Histopathological findings were compared with serum prostate specific antigen (PSA), histopathological stage, preoperative biopsy and postoperative prostatectomy Gleason score. Extended pelvic lymphadenectomy was compared with radical retropubic prostatectomy and standard lymphadenectomy in 700 consecutive patients in terms of complications, the number of lymph nodes dissected and operative time. RESULTS There were no significant differences in age, preoperative PSA or mean biopsy Gleason score in patients who underwent extended pelvic and standard lymphadenectomy. Metastases were diagnosed in 26 of the 124 patients (21%) and in 25 of the 100 high risk patients (25%) who underwent the extended procedure. A mean of 22 lymph nodes (range 15 to 31) were dissected. Metastases were identified in the internal iliac and external regions despite negative obturator lymph nodes. In 25 of the 26 patients (96.2%) with lymph node metastasis PSA was greater than 10.5 ng./ml and preoperative biopsy Gleason sum was 7 or greater. A intermediate risk of 2% for lymph node disease was noted in patients with serum PSA6.7 ng./ml. and biopsy Gleason score 4+3. There were no significant differences in regard to intraoperative and postoperative complications, lymphocele formation or blood loss in the 2 groups. CONCLUSIONS Extended pelvic lymphadenectomy is associated with a high rate of lymph node metastasis outside of the fields of standard lymphadenectomy in cases of clinically localized prostate cancer. Lymphadenectomy including the internal and external iliac lymph nodes should be performed in all patients with prostate cancer who are at high risk for lymph node involvement, as indicated by PSA greater than 10.5 ng./ml. and biopsy Gleason sum 7 or greater. In the low risk group pelvic lymphadenectomy can be omitted. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e543 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Senji Hoshi Yamagata, Japan More articles by this author Natuho Hayashi Yamagata, Japan More articles by this author Yuuta Kurota Yamagata, Japan More articles by this author Kiyotugu Hoshi Yamagata, Japan More articles by this author Akinori Muto Yamagata, Japan More articles by this author Kenji Numahata Yamagata, Japan More articles by this author Osamu Sugano Yamagata, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

First danish single-institution experience with radical prostatectomy: impact of surgical margins on biochemical outcome

This study aimed to investigate the impact of positive surgical margins (PSMs), stratified by location and extension, on biochemical outcome after radical retropubic prostatectomy (RRP). The study included data from 605 consecutive patients treated with RRP for localized prostate cancer. Patients with node-positive disease were excluded. Biochemical recurrence-free survival was calculated using the Kaplan-Meier method. Univariate and multivariate analysis was used to assess risk factors. The overall PSM rate was 35.4%. Eighty-three per cent (82.7%) of these had a single PSM, whereas 17.3% of patients had two or more PSMs. Apical PSMs were present in 42.5% and non-apical in 57.5%. The presence of any PSM had a significant impact on the risk of biochemical recurrence (BR) [hazard ratio (HR) = 3.3, p < 0.0001]. Compared with margin-negative patients, both apical and non-apical PSMs increased the risk of BR (HR = 2.1 and 4.2, p = 0.02 and p < 0.0001, respectively). The number of PSMs also influenced the risk of BR (one PSM: HR = 2.8, p < 0.0001, vs two or more PSMs: HR = 5.5, p < 0.0001). In multivariate analysis, pT category, PSA and prostatectomy Gleason score independently increased the risk of BR. In an exploratory multivariate analysis of pT2 tumours, the impact of apical PSMs on biochemical recurrence-free survival (BRFS) was not statistically significant, although with an HR of 2.1. Non-apical PSM was associated with a significantly increased risk of BR (HR = 3.4, p = 0.01). Number of PSMs did not influence the risk of BR in multivariate analysis. The presence of PSMs after RRP is associated with a higher risk of BR. Multiple and non-apical PSMs are associated with a significantly higher risk of BR compared to single and apical PSMs.

Cancer/Testis antigens as potential predictors of biochemical recurrence of prostate cancer following radical prostatectomy

BackgroundThe Cancer/Testis Antigens (CTAs) are an important group of proteins that are typically restricted to the testis in the normal adult but are aberrantly expressed in several types of cancers. As a result of their restricted expression patterns, the CTAs could serve as unique biomarkers for cancer diagnosis/prognosis. The aim of this study was to identify promising CTAs that are associated with prostate cancer (PCa) recurrence following radical prostatectomy (RP).MethodsThe expression of 5 CTAs was measured by quantitative multiplex real-time PCR using prostate tissue samples obtained from 72 patients with apparently clinically localized PCa with a median of two years follow-up (range, 1 to 14 years).ResultsThe expression of CTAs namely, CEP55, NUF2, PBK and TTK were significantly higher while PAGE4 was significantly lower in patients with recurrent disease. All CTAs with the exception of TTK were significantly correlated with the prostatectomy Gleason score, but none were correlated with age, stage, or preoperative PSA levels. In univariate proportional hazards models, CEP55 (HR = 3.59, 95% CI: 1.50-8.60), p = 0.004; NUF2 (HR = 2.28, 95% CI: 1.11-4.67), p = 0.024; and PAGE4 (HR = 0.44, 95% CI: 0.21-0.93), p = 0.031 were significantly associated with the risk of PCa recurrence. However, the results were no longer significant after adjustment for prostatectomy Gleason score.ConclusionsTo our knowledge, this is the first study to identify CTAs as biomarkers that can differentiate patients with recurrent and non-recurrent disease following RP and underscores its potential impact on PCa prognosis and treatment.

Prostate MRI: diffusion-weighted imaging at 1.5T correlates better with prostatectomy Gleason grades than TRUS-guided biopsies in peripheral zone tumours

To investigate the usefulness of Apparent Diffusion Coefficients (ADC) in predicting prostatectomy Gleason Grades (pGG) and Scores (GS), compared with ultrasound-guided biopsy Gleason Grades (bGG). Twenty-four patients with biopsy-proven prostate cancer were included in the study. Diffusion-weighted images were obtained using 1.5-T MR with a pelvic phased-array coil. Median ADC values (b0,500,1000 s/mm²) were measured at the most suspicious areas in the peripheral zone. The relationship between ADC values and pGG or GS was assessed using Pearson's coefficient. The relationship between bGG and pGG or GS was also evaluated. Receiver operating characteristic (ROC) curve analysis was performed to assess the performance of each method on a qualitative level. A significant negative correlation was found between mean ADCs of suspicious lesions and their pGG (r = -0.55; p < 0.01) and GS (r = -0.63; p < 0.01). No significant correlation was found between bGG and pGG (r = 0.042; p > 0.05) or GS (r = 0.048; p > 0.05). ROC analysis revealed a discriminatory performance of AUC = 0.82 for ADC and AUC = 0.46 for bGG in discerning low-grade from intermediate/high-grade lesions. The ADC values of suspicious areas in the peripheral zone perform better than bGG in the correlation with prostate cancer aggressiveness, although with considerable intra-subject heterogeneity. • Prostate cancer aggressiveness is probably underestimated and undersampled by routine ultrasound-guided biopsies. • Diffusion-weighted MR images show good linear correlation with prostate cancer aggressiveness. • DWI information may be used to improve risk-assessment in prostate cancer.

Can We Stop Prostate Specific Antigen Testing 10 Years After Radical Prostatectomy?

The risk of biochemical recurrence is inversely related to the relapse-free interval after radical prostatectomy. We examined predictors of late biochemical recurrence, and the relationship between timing of biochemical recurrence and long-term survival outcomes. Of 10,609 men treated with radical prostatectomy 1,684 had biochemical recurrence. We examined predictors of late biochemical recurrence (more than 10 years after radical prostatectomy), and calculated metastasis-free and cancer specific survival rates from the time of biochemical recurrence. In the subset of 1,583 men with an undetectable prostate specific antigen at 10 years we calculated actuarial metastasis-free and cancer specific survival estimates at 20 years after radical prostatectomy. Of the biochemical recurrence studied 77.0%, 16.6%, 4.9% and 1.5% occurred at 5 or less, greater than 5 to 10, greater than 10 to 15 and more than 15 years postoperatively. Late recurrence was associated with more favorable pathological features, as well as higher metastasis-free and cancer specific survival rates. For men with an undetectable prostate specific antigen at 10 years the actuarial probability of biochemical recurrence and metastasis at 20 years varied by stage and grade, with no metastases in patients with a prostatectomy Gleason score 6 or less. A single patient with an undetectable prostate specific antigen at 10 years died of prostate cancer within 20 years after radical prostatectomy. Men with an undetectable prostate specific antigen for more than 10 years have a low risk of subsequent biochemical recurrence, with correspondingly lower rates of metastasis and death. These patients should be counseled that their risk of subsequent cancer related morbidity and mortality is low. Furthermore, these results suggest that annual prostate specific antigen testing may be safely discontinued after 10 years for men with a prostatectomy Gleason score 6 or less and/or limited life expectancy.

The Potential Impact of Reproducibility of Gleason Grading in Men With Early Stage Prostate Cancer Managed by Active Surveillance: A Multi-Institutional Study

We evaluated the reproducibility of Gleason grading as relevant to the clinical treatment of men on active surveillance. Three sets of digital images of prostatic adenocarcinoma in biopsies were reviewed and assigned Gleason scores by a total of 11 pathologists from 7 institutions. Interobserver and intra-observer reproducibility were assessed for assignment of the highest Gleason pattern (3 vs 4 or higher). We also identified 97 consecutive patients on active surveillance. Prostate biopsy glass slides from 82 of the patients were available for re-review and the frequency of carcinoma requiring the distinction of tangentially sectioned Gleason pattern 3 from 4 was determined. Interobserver reproducibility for classic Gleason patterns was substantial (Light's κ 0.76). Interobserver reproducibility for the histological distinction of tangentially sectioned Gleason pattern 3 from Gleason pattern 4 was only fair (Light's κ 0.27). Intra-observer reproducibility ranged from 65% to 100% (mean 81.5%). Of the 82 patients on active surveillance 61 had carcinoma and 15 (24.5%) had a set of biopsies with at least 1 focus in which the distinction between tangentially sectioned Gleason pattern 3 and poorly formed pattern 4 glands had to be considered. The reproducibility of grading classic Gleason patterns is high. However, variability in grading occurred when distinguishing between tangentially sectioned pattern 3 glands and the poorly formed gland subset of pattern 4. Developing universally accepted histological and/or molecular criteria to distinguish these patterns and subsequently characterizing their natural history would be useful when treating patients on active surveillance.

Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer

Prostasomes are microvesicles (mean diameter, 150 nm) that are produced and secreted by normal and malignant prostate acinar cells. It has been hypothesized that invasive growth of malignant prostate cells may cause these microvesicles, normally released into seminal fluid, to appear in interstitial space and therewith into peripheral circulation. The suitability of prostasomes as blood biomarkers in patients with prostate cancer was tested by using an expanded variant of the proximity ligation assay (PLA). We developed an extremely sensitive and specific assay (4PLA) for detection of complex target structures such as microvesicles in which the target is first captured via an immobilized antibody and subsequently detected by using four other antibodies with attached DNA strands. The requirement for coincident binding by five antibodies to generate an amplifiable reporter results in both increased specificity and sensitivity. The assay successfully detected significantly elevated levels of prostasomes in blood samples from patients with prostate cancer before radical prostatectomy, compared with controls and men with benign biopsy results. The medians for prostasome levels in blood plasma of patients with prostate cancer were 2.5 to sevenfold higher compared with control samples in two independent studies, and the assay also distinguished patients with high and medium prostatectomy Gleason scores (8/9 and 7, respectively) from those with low score (≤ 6), thus reflecting disease aggressiveness. This approach that enables detection of prostasomes in peripheral blood may be useful for early diagnosis and assessment of prognosis in organ-confined prostate cancer.

Abstract 2815: Urine TMPRSS2:ERG for prostate cancer risk stratification in men with elevated serum PSA

Abstract Background: Over 1,000,000 men undergo prostate biopsy each year in the U.S., most for “elevated” serum PSA. Given the lack of sensitivity and specificity, and unclear mortality benefit of PSA testing, methods to individualize management of elevated PSA are needed. We evaluated urine expression of TMPRSS2:ERG, a gene fusion occurring in 50% of prostate cancers, for risk-stratifying men presenting for biopsy. Methods: TMPRSS2:ERG was measured by a clinical grade, transcription-mediated-amplification assay in prospectively collected whole-urine from 1,094 men undergoing biopsy at 10 academic and community clinics. Findings: Urine TMPRSS2:ERG was associated with indicators of clinically significant cancer at biopsy and prostatectomy, including tumor size, high prostatectomy Gleason score and upgrading at prostatectomy. TMPRSS2:ERG in combination with urine PCA3, improved the multivariate PCPT risk calculator performance for predicting cancer on biopsy (AUC in test set, 0.79 vs. 0.64, p&amp;lt;0.001). Using a three-class stratification, men in the highest and lowest TMPRSS2:ERG+PCA3 score groups had markedly different rates of cancer (69% vs. 21%, p&amp;lt;0.001), clinically significant cancer by Epstein criteria (61% vs. 15%, p&amp;lt;0.001) and high grade cancer (40% vs. 7%, p&amp;lt;0.001) on biopsy. Interpretation: Urine TMPRSS2:ERG, in combination with urine PCA3, enhances the utility of serum PSA for predicting prostate cancer and clinically relevant cancer on biopsy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2815. doi:10.1158/1538-7445.AM2011-2815

Abstract 899: TMPRSS2:ERG urine test identifies Gleason score upgrading and significant prostate cancer

Abstract Objective: In men diagnosed with prostate cancer (PCa) at biopsy, a major challenge is correctly stratifying those with indolent versus significant PCa for treatment selection. The extent and grade of PCa is assessed in part based on standard risk factors, biopsy Gleason score (bx GS) and the number of positive biopsy cores. However, due to under-sampling at biopsy, upgrading in Gleason score is often seen from biopsy to prostatectomy. In this study we evaluated a TMPRSS2:ERG (T2:ERG) urine test for its ability to identify significant cancer and upgrading at prostatectomy. Methods: Post-DRE urine specimens were prospectively collected from 218 men referred for prostatectomy. T2:ERG mRNA copies were quantified using a transcription-mediated amplification assay and normalized to PSA mRNA copies to calculate a T2:ERG score. The prototype T2:ERG urine assay detects the gene fusion mRNA isoform TMPRSS2 exon 1 to ERG exon 4. T2:ERG score was correlated to prostatectomy Gleason score (px GS) and significant cancer as defined by the Epstein criteria at prostatectomy. Results: Of 185 men scheduled for radical prostatectomy, 61 had low risk of significant cancer based on having bx GS&amp;lt;6 and % positive biopsy cores&amp;lt;33%, yet upon prostatectomy, 57% of these men were found to harbor a significant PCa. The T2:ERG assay identified an additional 31% prostatectomy significant cancer in the biopsy low-risk disease cancer group. In a multivariate model, adding T2:ERG to bx GS and % positive cores significantly increased the accuracy for predicting significant PCa at prostatectomy from 0.84 to 0.89 (p=0.0002). Sensitivity increased by 8% for detecting prostatectomy significant cancer when T2:ERG was added to these biopsy criteria (sens/spec=85%/87% vs 77%/87%). T2:ERG also significantly correlated with Gleason score upgrading from biopsy to prostatectomy (bx GS/px GS = 6/ 6 vs bx GS/px GS = 6/&amp;gt;7, p = 0.0076). At biopsy, 70 men were found to have low-grade cancer (bx GS&amp;lt;6), but upon prostatectomy, upgrading was seen in 50% of these men. T2:ERG was able to identify 40% of men with bx GS&amp;lt;6 that were later upgraded. Conclusions: A T2:ERG urine test may help identify significant cancers and Gleason score upgrading, and increase predictive accuracy when used in combination with currently available methods. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 899. doi:10.1158/1538-7445.AM2011-899

994 GLEASON SCORE UPGRADING AFTER PROSTATECTOMY DEPENDS ON TUMOR FOCUS CHARACTERISTICS IN PATIENTS DIAGNOSED VIA STANDARDIZED 12-CORE PROSTATE BIOPSY

You have accessJournal of UrologyProstate Cancer: Localized1 Apr 2011994 GLEASON SCORE UPGRADING AFTER PROSTATECTOMY DEPENDS ON TUMOR FOCUS CHARACTERISTICS IN PATIENTS DIAGNOSED VIA STANDARDIZED 12-CORE PROSTATE BIOPSY Michael Musch, Ulla Roggenbuck, Michael Sahm, Stephan Stoerkel, and Darko Kroepfl Michael MuschMichael Musch Essen, Germany More articles by this author , Ulla RoggenbuckUlla Roggenbuck Essen, Germany More articles by this author , Michael SahmMichael Sahm Essen, Germany More articles by this author , Stephan StoerkelStephan Stoerkel Wuppertal, Germany More articles by this author , and Darko KroepflDarko Kroepfl Essen, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1027AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Gleason grading heterogeneity has been observed in multifocal prostate cancer (PCA). We hypothesized that the existence of small secondary tumor foci representing the highest Gleason grade in the prostatectomy specimen contributes to Gleason score upgrading after prostatectomy. METHODS Between 12/00 and 10/06 a total of 931 PCA patients underwent radical retropubic prostatectomy. In 162 of these patients PCA was initially diagnosed via standardized 12-core transrectal prostate biopsy in our institution. Pathohistological examination of the prostatectomy specimen included determination of predominant Gleason grade and volume of all tumor foci. The correlation of biopsy and prostatectomy Gleason scores (2–6, 7, 8–10) was calculated. In addition, the influence of small secondary tumor foci representing the highest Gleason grade in the prostatectomy specimen on the incidence of Gleason score upgrading was examined. RESULTS Due to missing data 146 of the initial 162 patients were suitable for analysis. Based on the prostatectomy specimen Gleason scores 4–6 were assigned to 91 (62.3%) patients, Gleason score 7 to 42 (28.8%) and Gleason scores 8–10 to 13 (8.9%). Upgrading was observed in 24 (16.4%) and downgrading in 13 (8.9%) cases (kappa 0.49; 95% CI 0.35–0.63). In 76/146 (52.0%) patients a small secondary tumor focus showed the highest Gleason grade in the prostatectomy specimen. The Gleason grade of the largest tumor focus was consistent with the overall highest Gleason grade in 48.0% (70/146) of cases. The median volume of the 76 small secondary tumor foci was significantly smaller than the median volume of the 70 largest tumor foci (0.21cc [range 0.01–2.68] vs. 0.83cc [range 0.01–9.67]; p<0.0001). In the 76 patients with a small secondary tumor focus representing the highest Gleason grade upgrading was observed in 23 (30.3%) cases. In contrast, in the 70 patients in whom the largest tumor focus represented the highest Gleason grade upgrading was observed in only 1 (1.4%) case. In a multivariate logistic regression adjusting for PSA, total tumor volume and prostate volume existence of a small secondary tumor focus representing the highest Gleason grade in the prostatectomy specimen remained the only independent risk factor for Gleason score upgrading (p=0.0005). CONCLUSIONS In PCA patients diagnosed via standardized 12-core prostate biopsy Gleason score upgrading after prostatectomy is significantly more frequent when small secondary tumor foci represent the highest Gleason grade in the prostatectomy specimen. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e400-e401 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Musch Essen, Germany More articles by this author Ulla Roggenbuck Essen, Germany More articles by this author Michael Sahm Essen, Germany More articles by this author Stephan Stoerkel Wuppertal, Germany More articles by this author Darko Kroepfl Essen, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1791 IMPACT OF POSITIVE SURGICAL MARGINS ON CLINICAL OUTCOME FOLLOWING LAPAROSCOPIC RADICAL PROSTATECTOMY (LRP)–LONG TERM RESULTS

You have accessJournal of UrologyProstate Cancer: Localized1 Apr 20111791 IMPACT OF POSITIVE SURGICAL MARGINS ON CLINICAL OUTCOME FOLLOWING LAPAROSCOPIC RADICAL PROSTATECTOMY (LRP)–LONG TERM RESULTS Jonas Busch, Carsten Stephan, Carsten Kempkensteffen, Stefan Hinz, Annett Klutzny, Steffen Weikert, Kurt Miller, and Ahmed Magheli Jonas BuschJonas Busch Berlin, Germany More articles by this author , Carsten StephanCarsten Stephan Berlin, Germany More articles by this author , Carsten KempkensteffenCarsten Kempkensteffen Berlin, Germany More articles by this author , Stefan HinzStefan Hinz Berlin, Germany More articles by this author , Annett KlutznyAnnett Klutzny Berlin, Germany More articles by this author , Steffen WeikertSteffen Weikert Berlin, Germany More articles by this author , Kurt MillerKurt Miller Berlin, Germany More articles by this author , and Ahmed MagheliAhmed Magheli Berlin, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2141AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The role of positive surgical margins (PSM) in prostatectomy specimens for the prediction of biochemical recurrence (BCR) has been heavily debated in the medical literature. It is a general conception that PSM are an adverse finding. However, especially in LRP, on intermediate-term follow up, PSM have been shown to have a limited influence on BCR. The aim of this study was to investigate the impact of PSM on clinical outcome following LRP in patients with extended follow up. METHODS We reviewed the records of 1,920 patients who underwent LRP from 1999 to 2007. Clinical outcome of patients with and without PSM was compared using the log rank test. The independent predictive value of PSM on outcome when taking into account other predictors of BCR was investigated by Cox regression analysis. RESULTS Overall, 447 (23.3%) patients had a positive surgical margin. Mean postoperative follow up was 60.5 months. BCR-free survival at 10 years was 77 % and 54% for patients with and without PSM, respectively (p<0.001). On univariate Cox-regression analysis, radical prostatectomy Gleason score (p<0.001), surgical margin status (p<0.001), pathological stage (p<0.001), and PSA (p<0.001) were predictors of biochemical recurrence. On multivariable Cox-regression analysis, including all statistical significant variables from the univariate model, PSA (p=0.012), pathological stage (p<0.001), radical prostatectomy Gleason score (p<0.001) and surgical margin status (p=0.016) remained independent predictors of BCR. CONCLUSIONS In contrast to other investigators who showed a limited impact of surgical margin status on BCR rates in patients undergoing LRP, we demonstrated its independent predictive value for BCR in our large cohort of LRP patients with extended follow-up. This underlines the importance of meticulous surgical dissection in minimally-invasive prostate surgery to reduce positive surgical margins. Our results could potentially be transferred to robotic assisted RP, in which long-term follow-up is lacking. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e719-e720 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jonas Busch Berlin, Germany More articles by this author Carsten Stephan Berlin, Germany More articles by this author Carsten Kempkensteffen Berlin, Germany More articles by this author Stefan Hinz Berlin, Germany More articles by this author Annett Klutzny Berlin, Germany More articles by this author Steffen Weikert Berlin, Germany More articles by this author Kurt Miller Berlin, Germany More articles by this author Ahmed Magheli Berlin, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...