Detection of intraductal carcinoma in prostate cancer patients with small tumor volume.

OBJECTIVES: The purpose of this study was to investigate intraductal carcinoma of the prostate (intraductal carcinoma) and significant cancer (SC) in patients with small tumor volume (<0.5 cm3 ) in prostatectomy specimens. METHODS: Data from 639 patients undergoing radical prostatectomy between April 2006 and December 2017 at Chiba University Hospital and 2 affiliated institutions were retrospectively reviewed. Tumor volume in prostatectomy specimens was measured, and with a tumor volume of less than 0.5 cm3 , the presence of intraductal carcinoma and SC was examined. SC was defined as one that did not meet the definition of pathological insignificant cancer (organ-confined cancer, Grade Group 1, tumor volume < 0.5 cm3 ). The number of patients who met four active surveillance (AS) protocols was also examined. RESULTS: A total of 83 patients with tumor volume < 0.5 cm3 were identified in this study population (SC: 43 patients [52%], intraductal carcinoma: 5 patients [6%]). The median follow-up was 34.6 months (range: 18-57 months). Four (5%) developed biochemical recurrence. The number of positive biopsy cores ≥ 2 was an independent predictor of SC in patients with tumor volume < 0.5 cm3 (hazard ratio: 4.39; 95% confidence interval: 1.67-11.56; p = 0.003). In tumor volume < 0.5 cm3 , tumor volume was significantly correlated with the International Society of Urological Pathology Grade Group (1 vs. 4-5, p = 0.002) and the presence of intraductal carcinoma (p = 0.004). In intraductal carcinoma-positive cases, four of five patients (80%) had the predictor of SC, which was two or more positive biopsy cores. Of the four AS protocols, the criteria for Prostate Cancer Research International: Active Surveillance were met most frequently in 46 cases (55%) of tumor volume less than 0.5 cm3 if targeted biopsy by magnetic resonance imaging was available. CONCLUSION: The results of the present study suggest that intraductal carcinoma was present even in cases with small tumor volumes. Grade Group and intraductal carcinoma showed a positive correlation with tumor volume.

TMPRSS2-ERG gene fusion is rare compared to PTEN deletions in stage T1a prostate cancer.

T1a prostate cancers (cancer found incidentally in transurethral resection, <5% of the tissue) are indolent tumors of the transition zone. The overexpression of ERG and the inactivation of PTEN have been shown to be important drivers of carcinogenesis in large series of prostate cancer, but the genetics of transition zone tumors have not been well characterized. We evaluated the status of ERG and PTEN in formalin-fixed paraffin-embedded tissue using immunohistochemical and FISH analysis in 54 T1a transition zone tumors. The protein expression of ERG was determined using a rabbit monoclonal antibody and nuclear staining was scored as positive or negative. The genomic status of ERG was determined using three colored FISH using an ERG-TMPRSS2 tri-color probe set. The protein expression of PTEN was determined using a rabbit monoclonal antibody and cytoplasmic, and nuclear staining was scored as positive or negative. The genomic status of PTEN was determined using dual color FISH with a PTEN probe and a CEP10 probe. We found ERG rearrangement in 2 of 54 tumors (4%), one with protein overexpression by immunohistochemistry. PTEN inactivation was seen in 13 of 54 tumors (24%). Nine of the 13 PTEN alleles were inactivated by hemizygous deletion. No homozygous PTEN deletion was observed. PTEN deletion and ERG rearrangement were mutually exclusive. ERG rearrangement was rare compared to peripheral zone tumors and to PTEN inactivation in T1a transition zone tumors. © 2016 Wiley Periodicals, Inc.

Validation of active surveillance criteria for pathologically insignificant prostate cancer in Asian men.

OBJECTIVES: To validate the ability of contemporary active surveillance protocols to predict pathologically insignificant prostate cancer among Asian men undergoing radical prostatectomy. METHODS: We retrospectively reviewed data on 132 patients eligible for any active surveillance criteria out of 450 patients that underwent radical prostatectomy at several institutions between 2006 and 2013. We validated the ability of seven contemporary active surveillance protocols to predict pathologically insignificant prostate cancer. Traditional and updated criteria to define pathologically insignificant prostate cancer were used. Predictive factors for pathologically insignificant prostate cancer were determined by logistic regression analysis. RESULTS: The predictive rate for updated pathologically insignificant prostate cancer of respective active surveillance criteria was 51% for Johns Hopkins Medical Institution, 41% for Prostate Cancer Research International: Active Surveillance Study, 39% for University of Miami, 32% for University of California, San Francisco, 32% for Memorial Sloan-Kettering Cancer Center, 31% for Kakehi and 27% for University of Toronto. Predictive rates for pathologically insignificant prostate cancer in Asian men were far lower than in USA men. On multivariate analysis, predictive factors of updated pathologically insignificant cancer was prostate volume (odds ratio 1.07, P = 0.004). By adding prostate volume to Prostate Cancer Research International: Active Surveillance Study criteria, the predictive rate for updated insignificant prostate cancer was improved up to 66.7%. CONCLUSIONS: Active surveillance can be carried out considering the clinical characteristics of prostate cancers depending on ethnicity, as current active surveillance criteria seem to have a lower predictive ability value of insignificant prostate cancer in Asian men compared with men in Western countries.

Optimal method for measuring tumor extent in needle biopsy specimens to identify small-volume prostate cancer.

OBJECTIVES: To compare various methods for measuring tumor extent in prostate biopsy specimens to identify small-volume prostate cancer. METHODS: A total of 100 radical prostatectomy specimens were retrospectively analyzed. Receiver operating characteristic analysis was used to compare the abilities of prostate-specific antigen density, and four measures of tumor extent in prostate biopsy specimens - positive core number, greatest percentage of cancer in a single core, greatest length of cancer in cores and total length of cancer in cores - to identify small volume prostate cancer. Four definitions of insignificant cancer volume were used in this analysis: index and total tumor volume <0.5 mL, index tumor volume <1.3 mL and total tumor volume <2.5 mL. Multivariate analysis was also used to evaluate variables for predicting small-volume prostate cancer. RESULTS: Total length of cancer in cores had the highest areas under the curve of all the measures defining small-volume prostate cancer: index tumor volume <0.5 mL (0.855), total tumor volume <0.5 mL (0.877), index tumor volume <1.3 mL (0.784) and total tumor volume <2.5 mL (0.818). On multivariate analysis total length of cancer in cores was an independent predictive factor for prostate cancers with index tumor volume <0.5 mL (P < 0.001), <1.3 mL (P < 0.001) and total tumor volume <0.5 mL (P < 0.001), respectively. CONCLUSION: Our data suggest that total length of cancer in cores is the optimal measure of tumor extent in prostate biopsy specimens for identifying small-volume prostate cancer.

Does cumulative prostate cancer length (CCL) in prostate biopsies improve prediction of clinically insignificant cancer at radical prostatectomy in patients eligible for active surveillance?

OBJECTIVES: To evaluate if cumulative prostate cancer length (CCL) on prostate needle biopsy divided by the number of biopsy cores (CCL/core) could improve prediction of insignificant cancer on radical prostatectomy (RP) in patients with prostate cancer eligible for active surveillance (AS). PATIENTS AND METHODS: Patients diagnosed with prostate cancer on extended (≥10 cores) biopsy with an initial prostate-specific antigen (iPSA) level of <15 ng/mL, clinical stage (cT) ≤ 2a, and highest biopsy Gleason score 3 + 3 = 6 or 3 + 4 = 7 with <3 positive cores who underwent RP were included in the study. The CCL/core and presence of insignificant cancer (organ-confined, volume <0.5 mL, Gleason score at RP ≤6) were recorded. pT2 prostate cancer with RP Gleason score ≤3 + 4 = 7 and volume <0.5 mL were categorised as low-tumour-volume organ-confined disease (LV-OCD). RESULTS: In all, 221 patients met the inclusion criteria: the mean age was 59 years and the median iPSA level was 4.5 ng/mL. The clinical stage was cT1 in 86% of patients; biopsy Gleason score was 3 + 3 = 6 in 67% (group 1) and 3 + 4 = 7 in 33% of patients (group 2). The maximum percentage of biopsy core involvement was <50 in 85%; the median CCL/core was 0.15 mm. Insignificant cancer was found in 27% and LV-OCD in 44% of patients. Group 2 was associated with higher number of positive cores, maximum percentage core involvement, total prostate cancer length, and CCL/core. Group 1 was more likely to have insignificant cancer (39%) or LV-OCD (54%) than group 2 (3% and 23%, respectively). Group 2 had significantly higher RP Gleason score and pathological stage. Univariate analysis of group 1 showed that the iPSA level, maximum percentage core involvement, prostate cancer length, and CCL/core were all significantly associated with insignificant cancer and LV-OCD. For group 2, the number of positive cores (1 vs 2) was also significantly associated with LV-OCD. On multivariate logistic regression analysis, maximum percentage core involvement of <50, and number of positive cores (1 vs 2) were independent predictors of insignificant cancer in group 1; biopsy Gleason score, maximum percentage core involvement of <50 and prostate cancer length of <3 mm or CCL/core of <0.2 mm were all independent predictors of LV-OCD in the whole population. The maximum percentage of core involvement of <50 and prostate cancer length of <3 mm or CCL/core of <0.2 mm were also independent predictors of LV-OCD in group 1 patients. CONCLUSION: In patients eligible for AS, a CCL/core of <0.20 mm was significantly associated with insignificant cancer and LV-OCD. However, when parameters of cancer burden were considered, CCL/core did not independently add any additional value for predicting insignificant cancer in patients with biopsy Gleason score 6. The CCL/core was an independent predictor of LV-OCD in the whole population and in group 1 patients, although the model including prostate cancer length showed slightly higher area under the receiver operating characteristic curve.

A negative multiparametric magnetic resonance imaging finding does not guarantee the absence of significant cancer among biopsy-proven prostate cancer patients: a real-life clinical experience.

PURPOSE: We analyzed the data of consecutive patients who had preoperative multiparametric magnetic resonance imaging (mpMRI) and underwent radical prostatectomy (RP) to evaluate the actual performance of mpMRI among biopsy-proven prostate cancer (PCa) patients in predicting favorable pathology in the real-life clinical setting. METHODS: Among a total 730 biopsy-proven PCa patients underwent RP, the preoperative mpMRIs of 534 patients were positive, demonstrating one or more PI-RADs V2 grade ≥ 2 lesion(s). Other 196 mpMRIs were classified as negative, without any suspicious lesion. Pathology was classified to be unfavorable when showing Gleason score (GS) 4/5 or pT3/N1 features. Significant cancer was defined as non-organ-confined, GS 4/5, or cancer volume of ≥ 0.5 mL. RESULTS: Among a total 196 negative preoperative mpMRI patients, final RP pathology showed that 20 (10.2%) had pT3 disease and 2 (1.0%) had pN1 disease. Regarding the pathologic Gleason score, 117 (59.7%) had GS 3 + 4 and 44 (22.4%) had GS ≥ 4 + 3. The rate of a favorable PCa and an insignificant cancer was as low as 14.3% and 10.2%. Even among only the 101 D'Amico low-risk patients with negative MRI, the rates of a favorable pathology and an insignificant cancer were only 18.2% and 12.7%. The sensitivity, specificity, positive, and negative predictive value of mpMRI to predict a significant cancer were 74.3%, 45.5%, 95.5%, and 10.2%, respectively. CONCLUSIONS: In the real-life clinical setting, mpMRI demonstrated limited performance in the prediction of favorable and insignificant prostate cancer as a negative mpMRI could not guarantee the absence of unfavorable pathology among PCa patients.