Search

Purpose of review Pathomics, the fusion of digitalized pathology and artificial intelligence, is currently changing the landscape of medical pathology and biologic disease classification. In this review, we give an overview of Pathomics and summarize its most relevant applications in urology. Recent findings There is a steady rise in the number of studies employing Pathomics, and especially deep learning, in urology. In prostate cancer, several algorithms have been developed for the automatic differentiation between benign and malignant lesions and to differentiate Gleason scores. Furthermore, several applications have been developed for the automatic cancer cell detection in urine and for tumor assessment in renal cancer. Despite the explosion in research, Pathomics is not fully ready yet for widespread clinical application. Summary In prostate cancer and other urologic pathologies, Pathomics is avidly being researched with commercial applications on the close horizon. Pathomics is set to improve the accuracy, speed, reliability, cost-effectiveness and generalizability of pathology, especially in uro-oncology.

Recent studies have demonstrated that most patients with mucinous prostatic adenocarcinoma may have a better prognosis than those with conventional prostatic adenocarcinoma; however, the mechanism remains unclear. Loss of phosphatase and tensin homolog (PTEN) expression is known to occur in aggressive high-grade prostatic adenocarcinoma, but expression in mucinous prostatic adenocarcinoma has not been well characterized. In this study, we sought to analyze PTEN expression in mucinous prostatic adenocarcinoma, prostatic adenocarcinoma with mucinous features, and the adjacent conventional prostatic adenocarcinoma. Cases were obtained from the Urologic Pathology files of 3 major academic institutions. Ninety-two cases were identified. PTEN expression was positive in the mucinous component of 79/92 (86%) cases. Concordant positive expression of PTEN between mucinous prostatic adenocarcinoma, prostatic adenocarcinoma with mucinous features, and the adjacent conventional prostatic adenocarcinoma was present in 60/79 (76%) cases. The fact that 86% of cases of mucinous prostatic adenocarcinoma and prostatic adenocarcinoma with mucinous features were positive for PTEN despite relatively high Gleason scores is in keeping with the fact that these tumors may be less aggressive than conventional prostatic adenocarcinoma without associated extraluminal mucinous components. In 76% of cases, the expression profiles (PTEN positive or negative) of mucinous prostatic adenocarcinoma and prostatic adenocarcinoma with mucinous features were similar to those of the adjacent conventional prostatic adenocarcinoma, implying that they may likely be clonal from a molecular standpoint. In addition, it is highly conceivable that the subset of PTEN-negative mucinous tumors may still have a relatively good prognosis due to a different/PTEN-independent protective pathway or mechanism.

ISUP (International Society for Urologic Pathology) and WHO adopted prognostic Grade Groups 1 to 5 that simplify prostate cancer grading for prognosis. Grade Group 4 is Gleason score 8 cancer, which is heterogeneous, and it encompasses Gleason score 4 + 4 = 8, 3 + 5 = 8 and 5 + 3 = 8. The comparative prognostic implications of these various Gleason scores had not been studied by urological pathologists after a re-review of slides.Patients with a highest biopsy Gleason score of 3 + 5 = 8 or 4 + 4 = 8 were included in the study. Controls were cases with a highest Gleason score of 4 + 3 = 7 or 9-10. A total of 423 prostatic biopsy cases accessioned from 2005 to 2013 at 2 institutions were reviewed. Clinicopathological findings and followup (median 33.4 months) were assessed.Among Gleason score 8 cancers the cancer status outcome in 51 men with Gleason score 3 + 5 = 8 was marginally worse than in 114 with Gleason score 4 + 4 = 8 (p = 0.04). This was driven by a persistent nonmetastatic (after radiation/hormone therapy) cancer rate of 37% among Gleason score 3 + 5 = 8 cases vs 24% among Gleason score 4 + 4 = 8 cases. Conversely, cancer specific survival at 36-month followup was 97.8% in 3 + 5 cases vs 92.6% in 4 + 4 cases but this was not significant (p = 0.089). Cancer specific survival in the Gleason score 8 group was dichotomized by the presence of cribriform growth (p = 0.018). All Gleason score categories did not differ in the fraction of biopsy cores positive, clinical presentation or pathological findings, including the frequency of Gleason pattern 5, in 70 patients who underwent prostatectomy.Using the most current standards of prostate cancer grading the prognosis is not different in Gleason score 3 + 5 = 8 and 4 + 4 = 8 cancers. This justifies including both in Grade Group 4.

Objectives: This study was designed to estimate the improved accuracy of prostate cancer (PCa) detection resulting from additional midline biopsies of the peripheral zone in first standard biopsy. Patients and Methods: Patients were classified into 3 groups: 402 cases of sextant biopsies (1995-2002), 488 cases of 8-core biopsies with 2 additional midline biopsies (2003-2006), and 391 cases of 10-core biopsies with 4 additional midline biopsies (2007-2012). The positive rate of each number of biopsies and changes in positive rates associated with prostate specific antigen (PSA) ranges were estimated. Results: The positive rate of core biopsy significantly improved with increasing numbers of core biopsies (30.1% for sextant, 43.4% for 8-core biopsies, and 53.1% for 10-core biopsies). The accuracy of biopsies for each PSA range also significantly improved (22.3% for sextant, 30.0% for 8-core biopsies, and 43.2% for 10-core biopsies in the PSA gray zone [4.01-10 ng/ml]; and 26.5% for sextant, 52.9% for 8-core biopsies, and 71.8% for 10-core biopsies in the intermediate PSA range [10.1-20 ng/ml]). In the 208 cases with positive results using the 10-core biopsy method, the distribution of Gleason scores did not differ between the sextant only group and the midline site only group. Conclusions: Additional midline biopsy was associated with improved accuracy of positive core biopsies in Japanese patients with a PSA range of 4.01-20 ng/ml.

A little deeper resection was done during transurethral resection of the prostate (TURP) for benign prostate hyperplasia (BPH) to fill the disparities of reported prevalence rates between latent and incidental prostate cancer, as well as in order not to overlook clinically significant incidental cancer.We performed TURP in 995 patients who were diagnosed to have BPH. With a routine TUR setup, first most of the transition and central zones were resected. Then a slightly deeper resection of the residual adenoma and the peripheral zone than in the usual TURP was made. Pathological specimens were collected from 6 different parts.Incidental cancer was diagnosed in 226 patients (22.7%). Gleason scores were distributed as follows: 6 or less in 150 cases (66.4%), 7 in 68 cases (30.1%), and 8 in 8 cases (3.5%). Even in the patients with lower prostate specific antigen (PSA), patients with incidental cancer and Gleason scores of 7 or more were 142 (21.2%) and 41 (28.9%) respectively at 0PSA4.0 ng/ml, and 95 (18.7%) and 26 (27.4%) respectively at 0PSA2.5 ng/ml. Multifocal/diffuse cancer was detected in 84 (37.2%) patients.With our method of advanced TURP, we detected incidental cancer at almost the same rate as reported in latent cancer. When TURP is performed, incidental cancer as well as to relieve voiding difficulties must not be overlooked, because there must be a considerable number of clinically significant incidental cancer of higher Gleason scores, and of multifocal/diffuse lesions.

purpose was to evaluate the performance of cognitive target MRI-TRUS fusion biopsies of MRI detected PI-RADS (Prostate Imaging Reporting and Data System) 4 and 5 lesions. The correlation between the apparent diffusion coefficient (ADC) and Gleason outcome was also studied. METHODS: 52 consecutive patients in the period from 12/ 2013-06/2014 with increased PSA and PI-RADS 4 or 5 lesions on MRI (3T Siemens-skyra, protocol and reporting according to ESUR guidelines) were included. All patients underwent target biopsies using TRUS (B&K, Falcon 2101) which were performed by the same urologist and radiologist with MRI images and structured report available. In patients with a negative biopsy, MRI-guided biopsy was advised. A bi-variate pearson correlation was performed for ADC and Gleason outcome in positive cases. RESULTS: A total of 52 patients were included (16 PIRADS 4 and 36 PIRADS 5 lesions). Mean PSA and PSA-density value was respectively 9,88 (SD 6,1) and 0.20 (SD 0.11). Mean lesion size was 13.95 mm (SD 6.26 mm). 9 PIRADS 4 lesions (56%) and 26 PIRADS 5 lesions (72%) were found positive for prostate cancer. The correlation between the ADC value and histology outcome is showed in figure 1. Overall 67% of the biopsies were positive for prostate cancer using cognitive target MRI-TRUS fusion biopsies. The additional MRI-guidedbiopsies that were performed from the negative cases proved in 50% to be malignant (0/2 for PI-RADS 4 and 3/4 for PI-RADS 5 lesions). A significant correlation between ADC and Gleason value was found (-0.363 P

significantly higher in AA (Median 6.72 versus 6.35, p 1⁄4 0.04). No differences in age or stage of disease were detected between groups (p > 0.05). In Caucasians, MIC 1 expression was positively associated with PSA (p 0.0001), while Gleason score was positively associated with PSA (p < 0.05) and age (p < 0.05). Log transformed PSA and MIC 1 were used for valid inferences. Thus, higher levels of MIC 1 expression and higher Gleason scores were associated with older patients when limiting our sample to Caucasians. In AA, however, both older and younger patients had highly expressed MIC 1 and high Gleason scores. CONCLUSIONS: Although a detailed sample analysis is required, these observations indicate that addition of MIC 1 may help to improve the diagnostic capability of an aggressive stage of prostate cancer at least in African American men.

We analyzed current practice patterns and determined whether urologists are diagnosing and staging prostate cancer in accordance with one another and with available literature.An anonymous questionnaire was mailed to 1,500 randomly selected practicing American Urological Association members throughout the United States, categorized according to practice setting and decade of residency training completion.There were 624 respondents (41.6%). Annual routine prostate cancer detection is being aimed toward the right of the age spectrum. More than half of respondents use age specific prostate specific antigen (PSA), while fewer than half use PSA density in determining need for biopsy. The vast majority will perform radical prostatectomy on patients whose age suggests that they will not benefit from surgery. High PSA values and Gleason scores often are disregarded as independent precluding factors when deciding to perform radical prostatectomy. Computerized tomography and radionuclide bone imaging are used routinely far in excess of what the literature suggests is appropriate. Regardless of preoperative staging results, most urologists still perform lymphadenectomy with all radical prostatectomies.Discrepancies exist in practice patterns between urologists as well as inconsistencies in logic within individuals. There is little variation between individuals in different practice settings. Our results reflect the often confusing and conflicting data published during the last decade.

To evaluate a relationship between Gleason scores and Tc-99m HMDP bone imaging findings, data from 48 men (aged 45 to 77; mean, 67) with prostate carcinoma who had a bone imaging study at the time of presentation were reviewed. Cumulative Gleason scores were divided into two groups: high scores (6-10), 32 men; low scores (2-5), 16 men. Of the 32 men with high Gleason scores, 15 tested positive for multiple metastases and 17 tested negative. Tumors of the 16 men with low Gleason scores were negative for metastasis. A chi-square association between Gleason scores and the presence of metastases, either of a superscan pattern or multiple metastases, was 10.9 (1 df, P less than 0.001). The results indicate that a superscan pattern or multiple metastases were found exclusively in the bone images of patients with high histologic grades; bone images negative for metastases were associated with low-grade tumors. We conclude that positive bone imaging for metastases at the initial scan occurs only in patients who have high Gleason scores, that patients with high Gleason scores might or might not have skeletal metastasis, and that skeletal metastasis is not predictable in patients with low Gleason scores.

Purpose: We compared biochemical control rates of 3D conformal radiation therapy (3DCRT) plus neoadjuvant hormonal therapy (NHT) with those of prostate 3DCRT alone. We also examined the effect that two definitions of biochemical failure had on the comparison. Patients and Methods: We studied 126 men with stage T1-3B prostate cancer, who were treated with 3DCRT (Median dose of 72.0 Gy prescribed to the PTV) to the prostate alone (minimum follow-up duration of 1 year). Thirty-nine men received 4 to 6 months of NHT and 87 had 3DCRT alone. Hormonal therapy consisted of a LHRH agonist +/- an anti-androgen. We subdivided the patients into risk categories according to their baseline PSA and Gleason score: Low risk (Gleason Scores >7 and baseline PSA >10), Intermediate risk (Gleason Scores >7 and baseline PSA ≥10 or Gleason Scores ≥7 and baseline PSA >10), and High risk (Gleason Scores ≥7 and baseline PSA ≥10). We used two definitions of biochemical failure. First we defined failure according to the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus statement. In the second analysis, biochemical failure was defined as three serial rises in the PSA with a rise above 1.5 ng/ml. Results: According to the ASTRO definition, the use of neoadjuvant hormonal therapy resulted in a significantly lower PSA control rate in low and intermediate risk patients (P = .0028). When the data was reanalyzed using the second definition for PSA failure, the results were reversed, in that the biochemical outcomes of HT patients were better than the outcomes of patients who received 3DCRT alone. Conclusion: This reversal of outcome indicates that treatment outcome depends on definition of biochemical failure in patients receiving NHT. Given this limitation, it is important that ASTRO address the use of hormonal therapy in devising a new consensus statement defining biochemical failure.

422 THE QUEST TO FIND HIGH GRADE PROSTATE CANCER: ARE WE FAILING? Sarah Fitch*, Michael S Cohen, Robin Ruthazer, John A Libertino. Burlington, MA, and Boston, MA. INTRODUCTION AND OBJECTIVE: With the advent of PSA screening and a standard 12-core needle prostate biopsy, prostate cancer is being diagnosed with increasing frequency at an earlier stage of disease. Therefore, we are interested in determining if our ability to diagnose high grade prostate cancer has improved. METHODS: The biopsy and prostatectomy Gleason scores