Large and small cribriform architecture have similar adverse clinical outcome on prostate cancer biopsies.

AIMS: Invasive cribriform and intraductal carcinoma (IDC) are associated with adverse outcome in prostate cancer patients, with the large cribriform pattern having the worst outcome in radical prostatectomies. Our objective was to determine the impact of the large and small cribriform patterns in prostate cancer biopsies. METHODS AND RESULTS: Pathological revision was carried out on biopsies of 1887 patients from the European Randomised Study of Screening for Prostate Cancer. The large cribriform pattern was defined as having at least twice the size of adjacent benign glands. The median follow-up time was 13.4 years. Hazard ratios for metastasis-free survival (MFS) and disease-specific survival (DSS) were calculated using Cox proportional hazards regression. Any cribriform pattern was found in 280 of 1887 men: 1.1% IDC in grade group (GG) 1, 18.2% in GG2, 57.1% in GG3, 55.4% in GG4 and 59.3% in GG5; the large cribriform pattern was present in 0, 0.5, 9.8, 18.1 and 17.3%, respectively. In multivariable analyses, small and large cribriform patterns were both (P < 0.005) associated with worse MFS [small: hazard ratio (HR) = 3.04, 95% confidence interval (CI) = 1.93-4.78; large: HR = 3.17, 95% CI = 1.68-5.99] and DSS (small: HR = 4.07, 95% CI = 2.51-6.62; large: HR = 4.13, 95% CI = 2.14-7.98). Patients with the large cribriform pattern did not have worse MFS (P = 0.77) or DSS (P = 0.96) than those with the small cribriform pattern. CONCLUSIONS: Both small and large cribriform patterns are associated with worse MFS and DSS in prostate cancer biopsies. Patients with the large cribriform pattern on biopsy have a similar adverse outcome as those with the small cribriform pattern.

Intraductal carcinoma has a minimal impact on Grade Group assignment in prostate cancer biopsy and radical prostatectomy specimens.

AIMS: Intraductal carcinoma (IDC) is an adverse histopathological parameter for prostate cancer outcome, but is not incorporated in current tumour grading. To account for its dismal prognosis and to omit basal cell immunohistochemistry, it has been proposed to grade IDC on the basis of its underlying architectural pattern. The aim of this study was to determine the impact of IDC grade assignment on prostate cancer biopsy and radical prostatectomy tumour grading. METHODS AND RESULTS: A cohort of 1031 prostate cancer biopsies and 835 radical prostatectomies were assigned a Grade Group according to the 2014 International Society of Urological Pathology guidelines, without incorporation of IDC in grading. Tumour grading was compared with a Grade Group in which IDC was graded on the basis of its underlying architecture. Of 1031 biopsies, 139 (13.5%) showed IDC. Grade assignment of IDC led to a Grade Group change in 17 (1.6%) cases: four of 486 (0.8%) Grade Group 1 cases were reclassified as Grade Group 2, nine of 375 (2.4%) Grade Group 2 cases were reclassified as Grade Group 3, and four of 58 (6.9%) Grade Group 4 cases were reclassified as Grade Group 5. IDC was observed in 213 of 835 (25.5%) radical prostatectomies, and its grading led to a change in tumour grade in five of 835 (0.6%) patients, with upgrading in two of 207 (1.0%) patients with Grade Group 1 cancer, in two of 420 (0.5%) patients with Grade Group 2 cancer, and in one of 50 (2%) patients with Grade Group 4 cancer. CONCLUSION: IDC grade assignment led to a Grade Group change in 1.6% of prostate biopsy specimens and in 0.6% of radical prostatectomy specimens. Although the inclusion of IDC in or the exclusion of IDC from the Grade Group might affect decision-making in individual patients, it has a minimal impact on overall prostate cancer management.

Characteristics and outcome of prostate cancer patients with overall biopsy Gleason score 3 + 4 = 7 and highest Gleason score 3 + 4 = 7 or > 3 + 4 = 7.

AIM: Prostate cancer heterogeneity and multifocality might result in different Gleason scores (GS) at individual biopsy cores. According to World Health Organisation/International Society of Urologic Pathology (WHO/ISUP) guidelines, the GS in each biopsy core should be recorded with optional reporting of overall GS for the entire case. We aimed to compare the clinicopathological characteristics and outcome of men with overall biopsy GS 3 + 4 = 7 with highest GS 3 + 4 = 7 (HI = OV) to those with highest GS > 3 + 4 = 7 (HI > OV). METHODS AND RESULTS: Prostate cancer biopsies from the European Randomised Study of Screening for Prostate Cancer (ERSPC) were revised according to WHO/ISUP 2014 guidelines (n = 1031). In total, 370 patients had overall GS 3 + 4 = 7, 60 of whom (16%) had had at least one biopsy core with GS 4 + 3 = 7 or 4 + 4 = 8. Men with higher GS than 3 + 4 (HI > OV) in any of the cores had higher age, prostate-specific antigen (PSA) level, number of positive biopsies, percentage tumour involvement, percentage Gleason grade 4 and cribriform or intraductal growth (all P < 0.05) than those with GS 3 + 4 = 7 at highest (HI = OV). In multivariable Cox regression analysis, including PSA, percentage positive biopsies and percentage tumour involvement, biochemical recurrence-free survival after radical prostatectomy (P = 0.52) or radiotherapy (P = 0.35) was not statistically different between both groups. CONCLUSION: Among patients with overall GS 3 + 4 = 7, those with highest GS > 3 + 4 = 7 had worse clinicopathological features, but clinical outcome was not statistically significant. Therefore, the use of overall GS instead of highest GS for clinical decision-making is justified, potentially preventing overtreatment in prostate cancer patients.

Presence of invasive cribriform or intraductal growth at biopsy outperforms percentage grade 4 in predicting outcome of Gleason score 3+4=7 prostate cancer.

Relative increase of grade 4 and presence of invasive cribriform and/or intraductal carcinoma have individually been associated with adverse outcome of Gleason score 7 (GS 7) prostate cancer. The objective of this study was to investigate the relation of Gleason grade 4 tumor percentage (%GG4) and invasive cribriform and/or intraductal carcinoma in GS 3+4=7 prostate cancer biopsies. We reviewed 1031 prostate cancer biopsies from the European Randomized Study of Screening for Prostate Cancer. In total 370 men had G3+4=7. The relation of invasive cribriform and/or intraductal carcinoma and %GG4 with biochemical recurrence-free survival (BCRFS) after radical prostatectomy (n=146) and radiation therapy (n=195) was analyzed using Cox regression. Invasive cribriform and/or intraductal carcinoma occurred in 7/121 (6%) patients with 1-10% GG4, 29/131 (22%) with 10-25%, and 52/118 (44%) with 25-50% GG4 (P<0.001). In crude analysis, both invasive cribriform and/or intraductal carcinoma (HR 2.72; 95% CI: 1.33-5.95; P=0.006) and 10-50% GG4 (HR 2.43; 95% CI: 1.10-5.37; P=0.03) were associated with BCRFS after prostatectomy. In adjusted analysis, invasive cribriform and/or intraductal carcinoma was an independent predictor for BCRFS (HR 2.40; 95% CI: 1.03-5.60; P=0.04) after prostatectomy, whereas percentage %GG4 (HR 1.00; 95% CI: 0.97-1.03; P=0.80) was not. While invasive cribriform and/or intraductal carcinoma (HR 2.58; 95% CI: 1.59-4.21; P<0.001) performed better than 10-50% GG4 (HR 1.24; 95% CI: 0.67-2.29; P=0.49) for prediction of BCRFS after radiation therapy, both parameters were insignificant in analysis adjusted for prostate-specific antigen (P=0.001), positive biopsies (P<0.001) and tumor volume (P=0.05). In conclusion, increased %GG4 is associated with invasive cribriform and/or intraductal carcinoma in GS 3+4=7 prostate cancer biopsies. Invasive cribriform and/or intraductal carcinoma is an independent parameter for BCR after prostatectomy, whereas %GG4 is not. The presence of invasive cribriform and/or intraductal carcinoma has to be included in pathology reports and should act as exclusion criterion for active surveillance.

Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy.

Invasive cribriform and intraductal carcinoma in radical prostatectomy specimens have been associated with an adverse clinical outcome. Our objective was to determine the prognostic value of invasive cribriform and intraductal carcinoma in pre-treatment biopsies on time to disease-specific death. We pathologically revised the diagnostic biopsies of 1031 patients from the first screening round of the European Randomized Study of Screening for Prostate Cancer (1993-2000). Ninety percent of all patients (n=923) had received active treatment, whereas 10% (n=108) had been followed by watchful waiting. The median follow-up was 13 years. Patients who either had invasive cribriform growth pattern or intraductal carcinoma were categorized as CR/IDC+. The outcome was disease-specific survival. Relationships with outcome were analyzed using multivariable Cox regression and log-rank analysis. In total, 486 patients had Gleason score 6 (47%) and 545 had ≥7 (53%). The 15-year disease-specific-survival probabilities were 99% in Gleason score 6 (n=486), 94% in CR/IDC- Gleason score ≥7 (n=356) and 67% in CR/IDC+ Gleason score ≥7 (n=189). CR/IDC- Gleason score 3+4=7 patients did not have statistically different survival probabilities from those with Gleason score 6 (P=0.30), while CR/IDC+ Gleason score 3+4=7 patients did (P<0.001). In multivariable analysis, CR/IDC+ status was independently associated with a poorer disease-specific survival (HR 2.6, 95% CI 1.4-4.8, P=0.002). We conclude that CR/IDC+ status in prostate cancer biopsies is associated with a worse disease-specific survival. Our findings indicate that men with biopsy CR/IDC- Gleason score 3+4=7 prostate cancer could be candidates for active surveillance, as these patients have similar survival probabilities to those with Gleason score 6.

Age and gender related differences in renal cell carcinoma in a European cohort.

PURPOSE: We evaluated the influence of age on gender related differences in the renal cell carcinoma presentation of patients operated on between 1995 and 2005 in a European country. We also assessed the trend of missing pathological data. MATERIALS AND METHODS: Data on all patients who underwent radical or partial nephrectomy for renal cell carcinoma during 1995 to 2005 in The Netherlands were retrospectively collected from the prospective PALGA (Pathological Anatomical National Automated Archive) database. Patients were divided into 5 cohorts based on age at surgery, including 40 or less, 41 to 50, 51 to 60, 61 to 70 and greater than 70 years. Variables evaluated were gender differences by age, and tumor size, subtype, stage and Fuhrman grade. RESULTS: A higher mean age in women was only observed in those older than 70 years (p <0.001). The male-to-female ratio was 2:1 at ages 41 to 60 years and 1.2:1 at greater than 70 years. Compared to men women had smaller tumors at ages 51 to 60 years (p = 0.03), stage pT3 was less common at age 41 years or greater (p = 0.02), and grade 2 was less common at age 61 years or greater (p <0.001). The incidence of tumors with missing data on stage (14.9%), subtype (52.2%) and grade (47.1%) decreased substantially during the study period (p <0.001). CONCLUSIONS: Older age in women than in men who present to surgery for RCC was only prevalent in those older than 70 years. The male-to-female ratio was almost equal in patients older than 70 years compared to a 2:1 ratio at ages 41 to 60 years. Women presented with fewer pT3 tumors than men at age 41 years or greater. Missing pathological data decreased significantly between 1995 and 2005.

Trends in epidemiology and treatment of upper urinary tract tumours in the Netherlands 1995-2005: an analysis of PALGA, the Dutch national histopathology registry.

OBJECTIVE: To evaluate changes in incidence, distribution of stage and grade as well as surgical treatment of upper urinary tract (UUT) tumours in the Netherlands from 1995 to 2005. PATIENTS AND METHODS: The PALGA registry, a nationwide network and registry of pathology encompassing all hospitals in the Netherlands, was used as primary data source. Pathology reports of all primary surgical procedures or biopsies without further surgical treatment within the next year, of cancer of the renal pelvis or ureter during the period 1995-2005, were included. The number of surgically treated UUT tumours per year, type of treatment and tumour characteristics were recorded. RESULTS: The population consisted of 2321 (67%) men and 1145 (33%) women with a mean age of 68.6 years. The distribution according to side was similar (left 44.1%, right 41.5%), bilateral tumours were rare (0.6%) and most tumours were in the renal pelvis (51.3%). Both the incidence and the incidence rate per 100 000 person-years increased during the study period (P < 0.001). Most urothelial cancers were grade 2 (40.9%) or 3 (41.2%) and stage Ta (30.6%), T1 (18.1%) or T3 (22.8%). There was an increase in grade 3 (P = 0.003) and muscle-invasive (P = 0.003) tumours in men only. Nephroureterectomy was performed in 41.3% of the cases and there was an increasing trend to endoscopic surgery (P = 0.019), although the absolute number was low. CONCLUSION: The incidence of surgically treated UUT tumours increased, with a significant trend towards more advanced disease in men. Most tumours were treated by nephroureterectomy or nephrectomy, although there was an increasing trend to endoscopic surgery.

Comparison of Tumor Volume Parameters on Prostate Cancer Biopsies.

CONTEXT.­: Prostate biopsy reports require an indication of prostate cancer volume. No consensus exists on the methodology of tumor volume reporting. OBJECTIVE.­: To compare the prognostic value of different biopsy prostate cancer volume parameters. DESIGN.­: Prostate biopsies of the European Randomized Study of Screening for Prostate Cancer were reviewed (n = 1031). Tumor volume was quantified in 6 ways: average estimated tumor percentage, measured total tumor length, average calculated tumor percentage, greatest tumor length, greatest tumor percentage, and average tumor percentage of all biopsies. Their prognostic value was determined by using either logistic regression for extraprostatic expansion (EPE) and surgical margin status after radical prostatectomy (RP), or Cox regression for biochemical recurrence-free survival (BCRFS) and disease-specific survival (DSS) after RP (n = 406) and radiation therapy (RT) (n = 508). RESULTS.­: All tumor volume parameters were significantly mutually correlated (R2 > 0.500, P < .001). None were predictive for EPE, surgical margin, or BCRFS after RP in multivariable analysis, including age, prostate-specific antigen, number of positive biopsies, and grade group. In contrast, all tumor volume parameters were significant predictors for BCRFS (all P < .05) and DSS (all P < .05) after RT, except greatest tumor length. In multivariable analysis including only all tumor volume parameters as covariates, calculated tumor length was the only predictor for EPE after RP (P = .02) and DSS after RT (P = .02). CONCLUSIONS.­: All tumor volume parameters had comparable prognostic value and could be used in clinical practice. If tumor volume quantification is a threshold for treatment decision, calculated tumor length seems preferential, slightly outperforming the other parameters.

Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups.

BACKGROUND: Grade groups (GGs) are an important parameter for therapeutic decision making in prostate cancer (Pca) patients. Invasive cribriform and/or intraductal carcinoma (CR/IDC) has an independent prognostic value for disease outcome, but are not included in the GG limiting their clinical use. OBJECTIVE: To perform a proof-of-principle study incorporating CR/IDC in the current GG. DESIGN, SETTING, AND PARTICIPANTS: All prostate biopsies of 1031 men with screen-detected Pca between 1993 and 2000 were reviewed for the current GG (ranging from 1 to 5) and CR/IDC. The cribriform grade (cGrade) was equal to the GG if CR/IDC was present and GG minus 1 if not. GG1 was cGrade1 if intraductal carcinoma was absent. INTERVENTION: Biopsy review for GG and CR/IDC. A total of 406 patients had received radical prostatectomy (RP), 508 radiotherapy (RT), 108 surveillance, and eight hormonal therapy, and the treatment was unknown for one patient. Outcome measurements and statistical analysis disease-specific survival (DSS), metastasis-free survival (MFS), and biochemical recurrence-free survival (BCRFS) after 15.1 yr (interquartile range 10.9-19.7 yr) follow-up were compared using Harrell's C-statistic. RESULTS AND LIMITATIONS: The biopsy GGs were 486 GG1, 310 GG2, 104 GG3, 64 GG4, and 67 GG5; cGrade distributions were 738 cGrade1, 102 cGrade2, 91 cGrade3, 58 cGrade4, and 42 cGrade5. The cGrade had a better discriminative value than the GG for DSS (C-index 0.79; 95% confidence interval 0.74-0.83 vs 0.76; 0.71-0.82) and MFS (0.79; 0.74-0.84 vs 0.77; 0.72-0.82). The discriminative value for BCRFS after RP and RT was similar for both models. Different diagnostic, such as use of sextant biopsies, and therapeutic strategies in the 1990s are the limitations of this study. CONCLUSIONS: The cGrade is a simple Pca grade modification with better discriminative values for DSS and MFS than the GG, particularly impacting decision making in men with current GG2 Pca. PATIENT SUMMARY: Microscopic grading is an important factor for decision making in prostate cancer (Pca) patients. We show that a simple grade modification better predicts Pca outcome and might improve treatment choices.

Reducing unnecessary biopsies while detecting clinically significant prostate cancer including cribriform growth with the ERSPC Rotterdam risk calculator and 4Kscore.

INTRODUCTION: The use of risk calculators predicting clinically significant prostate cancer (csCaP) on biopsy reduces unnecessary biopsies and overdiagnosis of indolent disease compared to a Prostate Specific Antigen (PSA) strategy. Updating these tools using more specific outcome measures and contemporary predictors could potentially lead to further reductions. Our objective was to assess clinical impact of the 4 kallikrein (4K) score, the Rotterdam Prostate Cancer Risk Calculator (RPCRC), and the combination of both for predicting csCaP based on the latest International Society of Urological Pathology grading system and cribriform growth pattern. MATERIALS AND METHODS: Our prospective cohort consisted of 2,872 men from the first screening round in the European Randomized Study of Screening for Prostate Cancer Rotterdam; biopsy indication PSA ≥ 3.0. The predictive performance of the 4Kscore, RPCRC, and the combination of RPCRC with 4Kscore were assessed with area under the receiver operator characteristic curve (AUC) and calibration plots. Decision curve analysis was used to evaluate the reduction of unnecessary biopsy and indolent CaP. RESULTS: The csCaP was present in 242 (8%) men, and indolent CaP in 578 (20%). The 4Kscore and RPCRC had similar high AUCs (0.88 vs. 0.87; P = 0.41). The 4Kscore-RPCRC combination improved AUC to 0.89 compared to 4Kscore (P < 0.01) and RPCRC (P < 0.01). The RPCRC and 4Kscore reduced the number of Bx with 42 and 44, respectively, per 100 men at risk compared to a ≥PSA 3.0 strategy without increasing missed csCaP. The RPCRC-4Kscore combination resulted in a slight additional net reduction of 3.3 biopsies per 100 men. CONCLUSIONS: The RPCRC and 4Kscore had similar reductions of unnecessary biopsies and overdiagnosis of indolent disease. Combination of both models slightly reduced unnecessary biopsies further. Gain in net benefit must, however, be weighed against additional costs and availability of tests.

Changes in the stage and surgical management of renal tumours during 1995-2005: an analysis of the Dutch national histopathology registry.

OBJECTIVE: To evaluate changes in the pathological characteristics, stage of primary renal tumours and their surgical management in the Netherlands during the period 1995-2005. METHODS: Extracts from the records of all patients who had surgery for primary renal tumours in the Netherlands during the period 1995-2005 were reviewed. Data were collected from PALGA, the nationwide network and archive of histocytopathology. The 2002 Tumour-Node-Metastasis and the three-tier Fuhrman grade were used for staging and grading. RESULTS: In all there were 12 471 operations for primary renal masses during the study period. The incidence of surgically removed renal cancers increased from 6.2 in 1995 to 7.5 cases per 100 000 inhabitants (P = 0.005) in 2005. The mean (sd, median) age of the patients was 63.3 (11.9, 65.0) years, with a male-to-female ratio of 3:2. The mean (sd) tumour size of malignant tumours decreased from 7.3 (3.6) to 6.9 (3.7) cm (P = 0.301). The percentage of benign removed tumours remained relatively stable (P = 0.056), with a mean of 5.4% of all resected tumours. There was an increase of grade 1 tumours; the incidence of T1 tumours increased from 36.6% to 44.2%, and advanced tumours decreased from 46.4% to 33.7%, respectively. The percentage of nephron-sparing surgery increased from 3.5% in 1995 to 10.1% (P = 0.003) in 2005, mainly in the T1a tumours. CONCLUSIONS: During the last decade there was an increase in the incidence of surgically treated renal tumours in the Netherlands. Tumours with favourable histopathological characteristics, low stage and grade, accounted for most of this increase. The percentage of surgically removed benign tumours remained stable. The use of nephron-sparing surgery increased during the last decade, especially in T1a tumours.

NADPH production by the pentose phosphate pathway in the zona fasciculata of rat adrenal gland.

Biosynthesis of steroid hormones in the cortex of the adrenal gland takes place in smooth endoplasmic reticulum and mitochondria and requires NADPH. Four enzymes produce NADPH: glucose-6-phosphate dehydrogenase (G6PD), the key regulatory enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD), the third enzyme of that pathway, malate dehydrogenase (MDH), and isocitrate dehydrogenase (ICDH). However, the contribution of each enzyme to NADPH production in the cortex of adrenal gland has not been established. Therefore, activity of G6PD, PGD, MDH, and ICDH was localized and quantified in rat adrenocortical tissue using metabolic mapping, image analysis, and electron microscopy. The four enzymes have similar localization patterns in adrenal gland with highest activities in the zona fasciculata of the cortex. G6PD activity was strongest, PGD, MDH, and ICDH activity was approximately 60%, 15%, and 7% of G6PD activity, respectively. The K(m) value of G6PD for glucose-6-phosphate was two times higher than the K(m) value of PGD for phosphogluconate. As a consequence, virtual flux rates through G6PD and PGD are largely similar. It is concluded that G6PD and PGD provide the major part of NADPH in adrenocortical cells. Their activity is localized in the cytoplasm associated with free ribosomes and membranes of the smooth endoplasmic reticulum, indicating that NADPH-demanding processes related to biosynthesis of steroid hormones take place at these sites. Complete inhibition of G6PD by androsterones suggests that there is feedback regulation of steroid hormone biosynthesis via G6PD.

Nephron-sparing surgery and percutaneous biopsies in renal-cell carcinoma: a global impression among endourologists.

BACKGROUND AND PURPOSE: On the one hand, nephron-sparing surgery (NSS) in small renal tumors is a safe and effective alternative to radical nephrectomy. On the other hand, the role of preoperative percutaneous needle biopsies (PNB) remains controversial. The purpose of this study was to evaluate the global current use of NSS in the treatment of renal-cell carcinoma (RCC) and the use of PNB among endourologists. MATERIALS AND METHODS: One thousand questionnaires were distributed during the 23rd World Congress of Endourology and SWL. Six questions regarding NSS and two questions regarding PNB were presented. Two hundred twenty-two questionnaires were returned. RESULTS: Of the respondents, 86.6% perform NSS for small renal tumors, whereas 13.4% perform only radical nephrectomies; 7.5% will consider NSS only in patients with a solitary kidney, and 0.5% will never consider NSS. The techniques for NSS, in descending order of preference, are partial nephrectomy, enucleation, cryoablation, radiofrequency ablation, and high-intensity focused ultrasound. The mean and maximum diameter of the tumor in patients with a normal contralateral kidney for which the urologists perform NSS is 4.0 cm. For a centrally located tumor, NSS is an option for 27.2% of the respondents. Regarding PNB in patients with suspicion of RCC, 55.9% of respondents never obtain renal biopsies in the preoperative assessment and 41.8% obtain them only in rare cases. The majority (90%) prefer histologic over cytologic biopsies. CONCLUSIONS: Nephron-sparing surgery is evolving to a global worldwide standard treatment for small renal tumors. Percutaneous needle biopsy remains a highly debated procedure.

Improving the Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculator for Initial Prostate Biopsy by Incorporating the 2014 International Society of Urological Pathology Gleason Grading and Cribriform growth.

BACKGROUND: The survival rate for men with International Society of Urological Pathology (ISUP) grade 2 prostate cancer (PCa) without invasive cribriform (CR) and intraductal carcinoma (IDC) is similar to that for ISUP grade 1. If updated into the European Randomized Study of Screening for Prostate Cancer (ERSPC Rotterdam) risk calculator number 3 (RC3), this may further improve upfront selection of men who need a biopsy. OBJECTIVE: To improve the number of possible biopsies avoided, while limiting undiagnosed clinically important PCa by applying the updated RC3 for risk-based patient selection. DESIGN, SETTING, AND PARTICIPANTS: The RC3 is based on the first screening round of the ERSPC Rotterdam, which involved 3616 men. In 2015, histopathologic slides for PCa cases (n=885) were re-evaluated. Low-risk (LR) PCa was defined as ISUP grade 1 or 2 without CR/IDC. High-risk (HR) PCa was defined as ISUP grade 2 with CR/IDC and PCa with ISUP grade≥3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We updated the RC3 using multinomial logistic regression analysis, including data on age, PSA, digital rectal examination, and prostate volume, for predicting LR and HR PCa. Predictive accuracy was quantified using receiver operating characteristic analysis and decision curve analysis. RESULTS AND LIMITATIONS: Men without PCa could effectively be distinguished from men with LR PCa and HR PCa (area under the curve 0.70, 95% confidence interval [CI] 0.68-0.72 and 0.92, 95% CI 0.90-0.94). At a 1% risk threshold, the updated calculator would lead to a 34% reduction in unnecessary biopsies, while only 2% of HR PCa cases would be undiagnosed. CONCLUSIONS: A relatively simple risk stratification tool augmented with a highly sensitive contemporary pathologic biopsy classification would result in a considerable decrease in unnecessary prostate biopsies and overdiagnosis of potentially indolent disease. PATIENT SUMMARY: We improved a well-known prostate risk calculator with a new pathology classification system that better reflects disease burden. This new risk calculator allows individualized prediction of the chance of having (potentially aggressive) biopsy-detectable prostate cancer and can guide shared decision-making when considering prostate biopsy.

Prostate cancer outcomes of men with biopsy Gleason score 6 and 7 without cribriform or intraductal carcinoma.

AIM OF THE STUDY: Gleason score (GS) 3 + 4 = 7 prostate cancer patients with presence of cribriform or intraductal carcinoma (7(+)) have a worse disease-specific survival than those without. The aim of this study was to compare the clinicopathologic characteristics and patient outcomes of men with biopsy GS 3 + 4 = 7 without cribriform or intraductal carcinoma (7(-)) to those with GS 3 + 3 = 6. MATERIALS AND METHODS: We included all patients from the first screening round of the European Randomized Study of Screening for Prostate Cancer (1993-2000) with a revised GS ≤ 3 + 4 = 7 (n = 796) following the 2014 International Society of Urological Pathology criteria. Relations with biochemical recurrence after radical prostatectomy or radiotherapy were analysed using log-rank testing and multivariable Cox regression analysis. RESULTS: In total, 486 patients had GS 6 and 310 had GS 7, 54 of whom had GS 7(+) (17%). During a median follow-up of 15 years, biochemical recurrence was seen in 61 (20%) GS 6, 54 (21%) GS 7(-) and 22 (41%) GS 7(+) patients (41%). Both biopsy GS 7(-) and 7(+) patients had significantly higher prostate-specific antigen levels, mean tumour percentage, percentage of positive cores and ≥cT3 than those with GS 6 (all P < .001). GS 7(-) patients did not have a poorer biochemical recurrence-free survival (BCRFS) after radical prostatectomy than GS 6 patients (log-rank P = .13), whereas those with GS 7(+) had (log-rank P = .05). In multivariable analyses, biopsy GS 7(-) was not associated with poorer BCRFS after radical prostatectomy (hazard ratio [HR], 1.3; 95% confidence interval [CI]: 0.67-2.4; P = .47) or radiotherapy (HR, 0.88; 95% CI: 0.51-1.5; P = .63). GS 7(+) was independently associated with poorer BCRFS after radical prostatectomy (HR, 3.0; 95% CI: 1.1-7.8; P = .03), but not after radiotherapy (HR, 1.2; 95% CI: 0.58-2.3; P = .67). CONCLUSIONS: Men with biopsy GS 7(-) prostate cancer have similar BCRFS after radical prostatectomy or radiotherapy to those with GS 6 and may be candidates for active surveillance as long as other inclusion criteria such as on PSA and tumour volume are met.

A decade of surgically removed small renal masses in the Netherlands: characteristics and trends in type of surgery and pathologic reporting.

PURPOSE: To assess nationwide the pathologic characteristics and trends in type of surgery and pathologic reporting in surgically managed renal tumors ≤ 4 cm. MATERIALS AND METHODS: A review of all pathologic reports of primary small renal masses operated on in the Netherlands during the period 1995 to 2005 was performed. The data source was a nationwide central archive of histocytopathology (Patologisch Anatomisch Landelijk Geautomatiseerde Archief). Tumors were stratified into three groups: ≤ 2, 2.1 to 3.0, and 3.1 to 4.0 cm. Age, sex, type of operation, and tumor pathology were analyzed. For renal-cell carcinomas, grade (3-tiers Fuhrman) and stage (2002 Tumor, Node, Metastasis) were assessed. Trends in type of surgery (radical or partial nephrectomy [PN]) and pathologic reporting during the study period were analyzed. RESULTS: Of all operated primary kidney tumors, 25.3% were ≤ 4.0 cm. The mean age of the patients was 63.1 years (standard deviation 11.7), and the male/female ratio was 3:2. Only 7.5% were benign tumors, and 9.8% were locally advanced (≥ T3). Tumors ≤ 3.0 cm were more likely to be benign (P = 0.006) and of lower stage (P ≤ 0.001) than tumors of 3.1 to 4 cm. PN was performed in 16.5% of the cases. Grade and subtype were reported in 55% of the cases. The rate of PNs performed increased during the decade. There was a trend in increased reporting of grade and subtype. CONCLUSIONS: A quarter of all the operated primary kidney tumors were ≤ 4 cm. Smaller tumors were more likely to be benign and of lower stage. A cutoff size regarding biologic aggressiveness can be settled at the 3 cm size. The PN rate increased along the decade. Grade and subtype reporting rates remained suboptimal, although a positive trend was noted.

Cytological punctures in the diagnosis of renal tumours: a study on accuracy and reproducibility.

BACKGROUND: Fine needle aspiration (FNA) cytology is under consideration as an auxiliary preoperative diagnostic technique in the diagnosis of renal masses. However, reports for FNA are contradictory with regard to diagnostic accuracy and applicability. OBJECTIVE: To evaluate the diagnostic accuracy and reproducibility of FNA from renal masses. DESIGN: FNAs performed in-bench (hematoxylin and eosin [H&E] stains) from 66 consecutive renal tumours (58 malignant and 8 benign tumours) were presented twice with a 6-mo interval to five pathologists with little experience in renal cytology. Pathologists were blinded for the results of the first round as well for the surgical specimen. The FNAs were stained for Papanicolaou and Giemsa. MEASUREMENTS: Diagnostic accuracy, concordance between smears and surgical specimens, and the generalized kappa for interobserver/intraobserver agreement were calculated. RESULTS AND LIMITATIONS: The number of nondiagnostic and nonconclusive cases ranged from 5-14% in the first and 3-8% in the second round. Overall accuracy varied between 73-89% and 71-91% for the first and second round, respectively. Sensitivity (72-97%) and positive predictive value (PPV) (93-100%) to classify a malignant tumour in both rounds was high. Sensitivity (25-100%) and PPV (28-100%) to classify a benign tumour was lower with a wide confidence interval. Overall concordance in subtyping ranged from 39-70% in the first, and from 52-74% in the second round. Interobserver agreement ranged from fair (kappa=0.039) to substantial (kappa=0.540) for the different subtypes. The intraobserver agreement (mean kappa=0.357, CI 95%=0.304-0.411) was moderate for all pathologists. The low number of benign tumours in this study precludes sound statements regarding the diagnostic accuracy of FNA to classify benignity. CONCLUSION: Despite the lack of experience in renal cytology, all pathologists showed a high diagnostic yield and good overall accuracy in distinguishing between malignant and benign tumours. Concordance in subtyping varied widely among pathologists and was reliable only for clear cell renal cell carcinoma (ccRCC). These results suggest that FNA may have a potential role in the diagnosis of renal tumours although its value in subtyping was limited in our setting.