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Objective: To establish predictors of clinical failure in patients operated with radical prostatectomy (RP) for clinically localized prostate cancer (PC) by analyzing the pathological characteristics of positive surgical margins (PSM). Patients and Methods: The RP specimens of 303 consecutive patients operated with RP between 1985 and 2009 were reviewed. PSM were analyzed with regard to the PSM length, location and multifocality and the Gleason score (GS) at the PSM. Results: Of the 163 patients with PSM, 79 (48%) progressed to clinical failure compared to 30 (22%) in the negative-margin-status group. In univariate analysis, a GS at the PSM ≥4 + 3 = 7 (p = 0. 013) and a PSM length >3.0 mm (p < 0.005) were significantly associated with higher clinical failure rates compared to a GS at the PSM ≤3 + 4 = 7 and ≤3.0 mm in extent, respectively. A linear extent of the PSM ≤3.0 mm appeared to have the same clinical outcome as in the group with a negative margin status. In multivariate analysis, a PSM length >3.0 mm remained an independent predictor of clinical failure. Conclusions: PSM length is an independent predictor of clinical failure following RP. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Several authors have previously reported that transrectal prostate biopsy has a false-negative rate of 20-30%, and that a number of prostate cancers missed on transrectal biopsy can be detected by transperineal biopsy. It has also been shown that most of these tumours are located anteriorly in the prostate gland. The present study showed a high rate of prostate cancer in patients with previous negative transrectal biopsies but elevated PSA levels, and that the cancers were located anteriorly in the prostate gland. Also, most of these cancers were clinically significant in patients that underwent RP, i.e. a high proportion of cancers were high-grade/high-stage tumours. We also showed that the transperineal biopsy technique can be applied successfully to patients with a closed anal orifice after previous surgery for rectal cancer. Transperineal biopsy can be done safely without routine antibiotic prophylaxis. OBJECTIVE To investigate the outcomes of transperineal prostate biopsies in patients with elevated prostate-specific antigen (PSA) levels and negative transrectal biopsies. The aim of this retrospective study was to evaluate the diagnostic yield of the transperineal biopsy approach in these patients, and to evaluate the pathology findings in subsequent radical prostatectomy (RP) specimens in patients undergoing RP., PATIENTS AND METHODS In all, 69 consecutive patients with previous negative transrectal biopsies but elevated PSA levels investigated at urological units in Norway who had been referred to The Norwegian Radium Hospital were included., The patients had undergone a mean (median; range) of 2.42 (2; 0-7) transrectal biopsies. The mean (range) age was 63.1 (42-78) years. The median (range) PSA level was 12 (4.3-229) ng/mL., The patients were examined with transperineal biopsy of the prostate between July 2007 and February 2009. The results of the transperineal biopsies were reviewed for Gleason biopsy score, and these were compared with the histopathology results of the RP specimens, i.e. final Gleason scores., Pathological stage of the prostate specimens and tumour volume were also reviewed., RESULTS Prostate cancer was found in the biopsies of 38 of 69 patients (55%)., In all, 20 of 38 patients had a Gleason score estimated at ≥3 + 4 = 7., In all, 26 patients underwent RP. The surgical specimens revealed pathological stage pT2c in 65%, pT3a in 27% and pT3b in 8% of the cases., In all, 23 of the 26 RP specimens showed a final Gleason score of ≥7. The vast majority of cancers detected were situated in the anterior/ventral portion of the prostate., CONCLUSIONS Transperineal biopsy of the prostate in patients with an elevated PSA level after negative transrectal prostate biopsies appears to be a feasible and important option for further investigation to detect prostate cancer., The present study shows that the transperineal biopsy allows good access of the anterior/ventral part of the prostate., Histopathology reports on the RP specimens obtained from the patients that underwent RP revealed significant cancer. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? It is known that a tertiary Gleason grade pattern 4 or 5 found in RP specimens has a negative impact on recurrence rate regarding biochemical relapse after radical prostatectomy. This is the first publication addressing clinical outcome in patients with a tertiary Gleason grade pattern 4 or 5 showing a negative influence on clinical failure rates. OBJECTIVE To investigate the impact of a tertiary Gleason grade (TGG) pattern 4 or 5 on clinical failure, as the presence of a TGG pattern 4 or 5 in radical prostatectomy (RP) specimens has been associated with biochemical failure., PATIENTS AND METHODS In all, 151 consecutive patients undergoing RP between 1985 and 2006 were reviewed, and 148 patients met study inclusion criteria., The RP specimens were pathologically re-examined and the presence of a TGG pattern 4 or 5 was recorded., The endpoint was clinical failure defined as local recurrence and/or development of metastasis at a mean follow-up of 108 months., Univariate analyses were performed using the Kaplan-Meier method. Multivariate analyses were performed using Cox proportional hazards regression., RESULTS Clinical failure was more likely among men with presence of a TGG pattern 4 or 5 than in men without a TGG pattern 4 or 5 ( P= 0.006). In the subgroup of patients with Gleason score 7 the presence of a TGG 5 was significantly associated with clinical failure rate ( P= 0.002)., In patients with Gleason score <7 or >7, a TGG pattern 4 or 5 was not associated with increased failure rates., Multivariate Cox regression analyses in patients with Gleason score 7 showed that a TGG pattern 5 was a statistically significant predictor of clinical failure when adjusting for pathological stage, surgical margin status, extraprostatic extension and seminal vesicle invasion (hazard ratio 4.03, 95% confidence interval 1.72-9.46; P= 0.001)., Further subgroup analyses showed that a TGG pattern 5 was associated with statistically higher clinical progression rates in patients with Gleason score 3 + 4 ( P= 0.03)., In patients with Gleason score 4 + 3, a TGG pattern 5 was associated with a trend towards a higher clinical progression rate, although this was not statistically significant ( P= 0.189)., CONCLUSION A TGG pattern 4 or 5 is associated with decreased clinical recurrence-free survival in Gleason score 7. [ABSTRACT FROM AUTHOR]

Objective. The presence of a tertiary Gleason grade (TGG) pattern 4 or 5 in radical prostatectomy (RP) specimens has been reported with adverse pathology and a higher biochemical relapse rate after RP. This study investigated the impact of a TGG pattern 4 or 5 on biochemical and pathological outcome in men operated with RP. Material and methods. The study reviewed 151 consecutive cases treated at the hospital between 1985 and 2006; 148 were included in the study. All prostatectomy specimens were re-examined by a genitourinary pathologist and among others parameters the presence of TGG pattern 4 or 5 was recorded. The hospital files were examined retrospectively for clinical follow-up data. Prostate-specific antigen (PSA) relapse was defined as two subsequent rising measurements above 0.20 ng/ml. The influence of a TGG pattern 4 or 5 on prognosis was assessed in a Cox proportional hazards regression model controlling for pathological stage, surgical margin (SM) status, seminal vesicle invasion (SVI) and extraprostatic extension (EPE). Results. Fifty-six patients (38%) experienced PSA relapse during follow-up. Twenty-one patients (58%) with a TGG pattern 4 or 5 had a biochemical relapse compared with 35 patients (31%) without TGG pattern 4 or 5. In the Cox regression model, TGG pattern 4 or 5 was an independent predictor of biochemical failure ( p = 0.020). Conclusions. In patients undergoing RP the presence of a TGG pattern 4 or 5 is an independent predictor for biochemical relapse. Consequently, the RP specimens should routinely be investigated for TGG pattern 4 or 5. [ABSTRACT FROM AUTHOR]

Background: The clinical outcome for the individual prostate cancer patient is often difficult to predict, due to lack of reliable independent prognostic biomarkers. We tested DNA ploidy as a prognostic factor for clinical outcome in 186 patients treated with radical prostatectomy. Methods: DNA ploidy was measured using an automatic image cytometry system and correlated with preoperative PSA, age at surgery, Mostofi grade, surgical margins and Gleason score. Results: The mean follow up time after operation was 73.3 months (range 2–176 months). Of the 186 prostatectomies, 96 were identified as diploid, 61 as tetraploid and 29 as aneuploid. Twenty-three per cent, 36% and 62% of the diploid, tetraploid and aneuploid cases respectively, suffered from relapse during the observation time. DNA ploidy, Gleason score, Mostofi grading, surgical margins and preoperative PSA were all significant predictors of relapse in a univariate analysis. On multivariate analysis, only Gleason score and DNA ploidy proved to be independently predictors of disease recurrence. Furthermore, among the 68 cases identified with Gleason score 7, DNA ploidy was the only significant predictor of disease recurrence. Conclusions: Our data suggest that DNA ploidy should be included as an important additive prognostic factor for prostate cancer, especially for patients identified with Gleason score 7 tumours. [ABSTRACT FROM AUTHOR]

Background Prostate biopsies targeted by elastic fusion of magnetic resonance (MR) and three-dimensional (3D) transrectal ultrasound (TRUS) images may allow accurate identification of the index tumor (IT), defined as the lesion with the highest Gleason score or the largest volume or extraprostatic extension. Objective To determine the accuracy of MR-TRUS image-fusion biopsy in characterizing ITs, as confirmed by correlation with step-sectioned radical prostatectomy (RP) specimens. Design, setting, and participants Retrospective analysis of 135 consecutive patients who sequentially underwent pre-biopsy MR, MR-TRUS image-fusion biopsy, and robotic RP at two centers between January 2010 and September 2013. Intervention Image-guided biopsies of MR-suspected IT lesions were performed with tracking via real-time 3D TRUS. The largest geographically distinct cancer focus (IT lesion) was independently registered on step-sectioned RP specimens. Outcome measurements and statistical analysis A validated schema comprising 27 regions of interest was used to identify the IT center location on MR images and in RP specimens, as well as the location of the midpoint of the biopsy trajectory, and variables were correlated. Results and limitations The concordance between IT location on biopsy and RP specimens was 95% (128/135). The coefficient for correlation between IT volume on MRI and histology was r = 0.663 ( p < 0.001). The maximum cancer core length on biopsy was weakly correlated with RP tumor volume ( r = 0.466, p < 0.001). The concordance of primary Gleason pattern between targeted biopsy and RP specimens was 90% (115/128; κ = 0.76). The study limitations include retrospective evaluation of a selected patient population, which limits the generalizability of the results. Conclusion Use of MR-TRUS image fusion to guide prostate biopsies reliably identified the location and primary Gleason pattern of the IT lesion in >90% of patients, but showed limited ability to predict cancer volume, as confirmed by step-sectioned RP specimens. Patient summary Biopsies targeted using magnetic resonance images combined with real-time three-dimensional transrectal ultrasound allowed us to reliably identify the spatial location of the most important tumor in prostate cancer and characterize its aggressiveness. [ABSTRACT FROM AUTHOR]