Abstract Background Intraductal carcinoma (IDC) of prostate is a distinct entity associated with higher Gleason score and poor prognosis. The prognostic significance of large cribriform Gleason ...pattern 4 (LC) in conjunction with IDC has not been previously investigated. The aim of our study was to determine the impact of IDC and LC on biochemical recurrence-free rate (bRFR) in a contemporary prostatectomy cohort. Methods Prostate cancers of 246 prostatectomies, median follow-up 130.6 months, were graded with the International Society of Urological Pathology (ISUP) 2005 modified Gleason score (GS) and assessed for the presence of LC and/or IDC. In 57 cases with LC and/or IDC, immunostaining was performed to distinguish LC and IDC. The Kaplan–Meier (KM) method was used to estimate 5-year bRFR probabilities. Cox proportional hazards models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Multivariable analysis showed that the presence of any amount of LC or IDC had a highly significant prognostic effect on bRFR (HR 2.98, 95% CI: 1.68–5.28, p = 0.0002) after adjusting for GS, surgical margin status and pathological stage. Although IDC alone tended to be associated with a worse prognosis, LC and IDC did not appear to be associated with a difference in bRFR when analysed separately. Conclusion We demonstrate that the presence of any amount of LC/IDC is a significant prognostic factor after adjusting for Gleason score and T stage in determining patient outcome and we advocate including the presence of either in routine pathology reporting.
To compare the performance of T2-weighted (T2w) imaging and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of the prostate gland in the localization of recurrent prostate cancer in ...patients with biochemical failure after external beam radiotherapy (EBRT).
T2-weighted imaging and DCE MRI were performed in 33 patients with suspected relapse after EBRT. Dynamic contrast-enhanced MRI was performed with a temporal resolution of 95 s. Voxels enhancing at 46 s after injection to a greater degree than the mean signal intensity of the prostate at 618 s were considered malignant. Results from MRI were correlated with biopsies from six regions in the peripheral zone (PZ) (base, mid, and apex). The percentage of biopsy core positive for malignancy from each region was correlated with the maximum diameter of the tumor on DCE MRI with a linear regression model.
On a sextant basis, DCE MRI had significantly better sensitivity (72% 21of 29 vs. 38% 11 of 29), positive predictive value (46% 21 of 46 vs. 24% 11 of 45) and negative predictive value (95% 144 of 152 vs. 88% 135 of 153 than T2w imaging. Specificities were high for both DCE MRI and T2w imaging (85% 144 of 169 vs. 80% 135 of 169). There was a linear relationship between tumor diameters on DCE MRI and the percentage of cancer tissue in the corresponding biopsy core (r = 0.9, p < 0.001), with a slope of 1.2.
Dynamic contrast-enhanced MRI performs better than T2w imaging in the detection and localization of prostate cancer in the peripheral zone after EBRT. This may be helpful in the planning of salvage therapy.
The objective of our study was to compare T2-weighted MRI alone and T2 combined with diffusion-weighted imaging (DWI) for the localization of prostate cancer.
T2-weighted imaging and DWI (b value = ...600 s/mm2) were performed in 49 patients before radical prostatectomy using an endorectal coil at 1.5 T in this prospective trial. The peripheral zone of the prostate was divided into sextants and the transition zone into left and right halves. T2 images alone and then T2 images combined with apparent diffusion coefficient (ADC) maps (T2 + DWI) were scored for the likelihood of tumor and were compared with whole-mount histology results. Fixed window and level settings were used to display the ADC maps. Only tumors with an area of more than 0.13 cm2 (> 4 mm diameter) and a Gleason score of > or = 6 were considered significant. The area under the receiver operating characteristic curve (A(z)) was used to assess accuracy.
In the peripheral zone, the A(z) value was significantly higher (p = 0.004) for T2 plus DWI (A(z) = 0.89) than for T2 imaging alone (A(z) = 0.81). Performance was poorer in the transition zone for both T2 plus DWI (A(z) = 0.78) and T2 (A(z) = 0.79). For the whole prostate, sensitivity was significantly higher (p < 0.001) with T2 plus DWI (81% 120/149) than with T2 imaging alone (54% 81/149), with T2 plus DWI showing only a slight loss in specificity compared with T2 imaging alone (84% 204/243 vs 91% 222/243, respectively).
Combined T2 and DWI MRI is better than T2 imaging alone in the detection of significant cancer (Gleason score > or = 6 and diameter > 4 mm) within the peripheral zone of the prostate.
Purpose We determined if the USPSTF recommendation against prostate specific antigen screening was associated with a change in biopsy and cancer detection rates. Materials and Methods We conducted a ...time series analysis (October 2008 to June 2013) of prostate biopsies performed at University Health Network (Toronto). Biopsies for active surveillance or solely targeting magnetic resonance imaging detected lesions were excluded from study. Interventional ARIMA models with step functions were used to examine changes in the number of biopsies performed and cancers detected per month. Low risk prostate cancer was defined as no Gleason pattern 4 or greater, 3 or fewer cores involved, or 1/3 or less of the total number of cores involved, and no core with greater than 50% cancer involvement. Intermediate to high grade prostate cancer was defined as Gleason 7-10. Results A total of 3,408 biopsies were performed and 1,601 (47.0%) prostate cancers were detected (low risk prostate cancer 563 16.5%, intermediate to high grade prostate cancer 914 26.8%). The median number of biopsies per month decreased from 58.0 (IQR 54.5–63.0) before the recommendations to 35.5 (IQR 27.0–41.0) afterward (p=0.003), while the median number of patients undergoing first-time biopsy decreased from 42.5 (IQR 37.5–45.5) to 24.0 (IQR 19.0–32.5, p=0.025). The median number of low risk prostate cancers detected per month decreased from 8.5 (IQR 6.5–10.5) to 5.5 (IQR 4.0–7.0, p=0.012), while the median number of intermediate to high grade prostate cancers per month decreased from 17.5 (IQR 14.5–21.5) to 10.0 (IQR 9.0–12.0, p <0.001). Conclusions After the USPSTF recommendation the number of biopsies performed (total and first-time), based on referrals from our catchment area, has decreased. This is likely due to decreased use of prostate specific antigen screening. Although it is encouraging that fewer low risk prostate cancers are being diagnosed, the sudden decrease in the detection rate of Gleason 7-10 prostate cancers is concerning.
Abstract Background A biologic rationale exists for the association between metabolic syndrome (MetS) and prostate cancer (PCa). However, epidemiologic studies have been conflicting. Objective To ...evaluate the association between MetS and the odds of PCa diagnosis in men referred for biopsy. Design, setting, and participants Patients without prior PCa diagnosis undergoing prostate biopsy were identified from a large prostate biopsy cohort (in Toronto, Canada). The definition of MetS was based on the most recent interim joint consensus definition, requiring any three of five components (obesity, elevated blood pressure, diabetes or impaired fasting glucose, low high-density lipoprotein-cholesterol, and hypertriglyceridemia). Both the individual components of MetS and the cumulative number of MetS components were evaluated. Outcome measurements and statistical analysis The outcomes were PCa detection overall, clinically significant PCa (CSPC; defined as any Gleason pattern ≥4, >50% involvement of a single biopsy core, or more than one of three total number of cores involved), and intermediate- or high-grade PCa (I-HGPC; Gleason 7–10). Tests for trend and multivariable logistic regression analyses were performed. Results and limitations Of 2235 patients, 494 (22.1%) had MetS. No individual MetS component was independently associated with PCa. However, increasing number of MetS components was associated with higher PCa grade ( p < 0.001), as well as progressively higher odds of PCa outcomes (three or more; ie, MetS) compared with no MetS components: Odds ratios were 1.54 for PCa overall (95% confidence interval CI, 1.17–2.04; p = 0.002), 1.56 for CSPC (95% CI, 1.17–2.08; p = 0.002), and 1.56 for I-HGPC (95% CI, 1.16–2.10; p = 0.003) in multivariable analyses. The main limitation is the retrospective design. Conclusions Although the individual MetS components are not independently associated with PCa outcomes, MetS is significantly associated with higher odds of PCa diagnosis, CSPC, and I-HGPC. There is a biologic gradient between the number of MetS components and the risk of PCa, as well as cancer grade. Patient summary Metabolic syndrome is a collection of metabolic abnormalities that increases one's risk for heart disease. Our study shows that an increasing degree of metabolic abnormality is also associated with an increased risk of diagnosis of overall and aggressive prostate cancer.
To investigate differences in apparent diffusion coefficient (ADC) and T2 values between dense and sparse regions in prostate cancer.
Eighteen patients (median age, 61 years; range, 44-72 years) gave ...informed consent for this retrospective Research Ethics Board-approved study. Prior to radical prostatectomy, ADC (b value, 600 sec/mm(2)) and T2 maps were obtained by using 1.5-T magnetic resonance (MR) imaging. Twenty-eight peripheral zone (PZ) tumors were reviewed by using whole-mount histologic findings, and regions assessed to contain primarily (>60%) normal PZ tissue were delineated. Tumors were categorized as "sparse" if more than 50% of their cross-sectional areas were these primarily normal PZ regions and were considered "dense" otherwise. Normal PZ tissue was outlined separately on the same section. Tumor and normal tissue outlines were transferred to corresponding ADC and T2 maps, and median values were calculated. Values were compared by using multiple regression analysis. Matched-pair tumor-to-normal tissue differences and log(2)-transformed ratios were assessed by using nonparametric tests.
Thirty-six percent (10 of 28) of tumors were sparse; 64% (18 of 28) were dense. For both overall and intrapatient comparisons, dense tumors had significantly lower ADC and T2 values than normal PZ tissue (P < .05), but no significant differences were observed between sparse tumors and normal tissue. Log(2)-transformed tumor-to-normal tissue ratios were significantly less than zero for dense tumors for both ADC and T2 (P < .01) measurements but not for sparse tumors. Both matched-pair differences and log(2)-transformed ratios were significantly different between sparse and dense tumors (P < .01). ADC and T2 values were moderately correlated (Pearson correlation coefficient range, r = 0.770-0.804).
Sparse prostate tumors have similar ADC and T2 values to those of normal PZ tissue. This may limit MR imaging detection and the assessment of tumor volume of some cancers.
Purpose Based on contemporary epidemiological and pathological characteristics of prostate cancer we explain the rationale for and concerns about focal therapy for low risk prostate cancer, review ...potential methods of delivery and propose study design parameters. Materials and Methods Articles regarding the epidemiology, diagnosis, imaging, treatment and pathology of localized prostate cancer were reviewed with a particular emphasis on technologies applicable for focal therapy, defined as targeted ablation of a limited area of the prostate expected to contain the dominant or only focus of cancer. A consensus summary was constructed by a multidisciplinary international task force of prostate cancer experts, forming the basis of the current review. Results In regions with a high prevalence of prostate specific antigen screening the over detection and subsequent overtreatment of prostate cancer is common. The incidence of unifocal cancers in radical prostatectomy specimens is 13% to 38%. In many others there is an index lesion with secondary foci containing pathological features similar to those found incidentally at autopsy. Because biopsy strategies and imaging techniques can provide more precise tumor localization and characterization, there is growing interest in focal therapy targeting unifocal or biologically unifocal tumors. The major arguments against focal therapy are multifocality, limited accuracy of staging, the unpredictable aggressiveness of secondary foci and the lack of established technology for focal ablation. Emerging technologies with the potential for focal therapy include high intensity focused ultrasound, cryotherapy, radio frequency ablation and photodynamic therapy. Conclusions Early detection of prostate cancer has led to concerns that while many cancers now diagnosed pose too little a threat for radical therapy, many men are reluctant to accept watchful waiting or active surveillance. Several emerging technologies seem capable of focal destruction of prostate tissue with minimal morbidity. We encourage the investigation of focal therapy in select men with low risk prostate cancer in prospective clinical trials that carefully document safety, functional outcomes and cancer control.
Abstract An increased incidence of low-risk prostate cancer (PCa) has led investigators to develop focal therapy as a management option for PCa. We evaluated the effects of focal laser ablation (FLA) ...on PCa tissue and the accuracy of magnetic resonance imaging (MRI) in determining ablated lesion volume by comparing the whole-mount histology and MRI in four patients that underwent FLA followed by radical prostatectomy. Ablated areas were characterized by homogeneous coagulation necrosis. The MRI-calculated ablated volume correlated well with histopathology. We found that FLA creates confluent ablation with no evidence of viable cells in treated regions. Postablation MRI is able to determine the ablation accurately.
Purpose Positive surgical margins have a negative impact on disease outcomes after radical prostatectomy, yet their prognostic value may vary depending on specific pathological characteristics. We ...examined the relationship of positive surgical margins to biochemical progression according to several clinicopathological features. Materials and Methods We analyzed data from 1,268 patients who underwent radical prostatectomy for clinically localized prostate cancer at our center between 1992 and 2008, and did not receive any neoadjuvant or adjuvant treatment. We examined the relation of age, pretreatment prostate specific antigen, pathological T stage, radical prostatectomy Gleason score, disease risk group and surgical margin status to biochemical progression-free survival. Results The overall positive surgical margin rate was 20.8% and median followup was 79 months. The impact of positive surgical margins was dependent on risk group. Biochemical progression-free survival was 99.6% for the negative surgical margin group vs 94.9% for the positive surgical margin group in low risk disease (log rank p = 0.53), 93.5% for the negative surgical margin group vs 83% for the positive surgical margin group in intermediate risk disease (log rank p <0.001) and 78.5% for the negative surgical margin group vs 57.1% for the positive surgical margin group in high risk disease (log rank p = 0.003). These differences remained significant in a multivariate Cox regression model adjusting for other clinicopathological features. Conclusions Positive surgical margins are an independent predictor of biochemical progression in patients with intermediate and high risk prostate cancer. Patients with low risk disease have a favorable long-term outcome regardless of margin status and may be candidates for expectant management even with positive surgical margins, sparing them the side effects and costs of treatment.
Prostate cancer risk calculators incorporate many factors to evaluate an individual's risk for prostate cancer. We validated two common North American-based, prostate cancer risk calculators.
We ...conducted a prospective, multi-institutional study of 2,130 patients who underwent a prostate biopsy for prostate cancer detection from five centers. We evaluated the performance of the Sunnybrook nomogram-based prostate cancer risk calculator (SRC) and the Prostate Cancer Prevention Trial (PCPT) -based risk calculator (PRC) to predict the presence of any cancer and high-grade cancer. We examined discrimination, calibration, and decision curve analysis techniques to evaluate the prediction models.
Of the 2,130 patients, 867 men (40.7%) were found to have cancer, and 1,263 (59.3%) did not have cancer. Of the patients with cancer, 403 (46.5%) had a Gleason score of 7 or more. The area under the concentration-time curve (AUC) for the SRC was 0.67 (95% CI, 0.65 to 0.69); the AUC for the PRC was 0.61 (95% CI, 0.59 to 0.64). The AUC was higher for predicting aggressive disease from the SRC (0.72; 95% CI, 0.70 to 0.75) compared with that from the PRC (0.67; 95% CI, 0.64 to 0.70). Decision curve analyses showed that the SRC performed better than the PRC for risk thresholds of more than 30% for any cancer and more than 15% for aggressive cancer.
The SRC performed better than the PRC, but neither one added clinical benefit for risk thresholds of less than 30%. Further research is needed to improve the AUCs of the risk calculators, particularly for higher-grade cancer.
