Prognostic Differences in ISUP Grade Group 4: a Systematic Review and Meta-Analysis.

The ISUP (Internal Society of Urologic Pathology) recently adopted a five-tiered prognostication system. There is evidence to suggest that the ISUP grade group 4 is a heterogeneous entity regarding prognosis. Our aim was to systematically examine the existing evidence to determine if outcome differences exist within the ISUP grade group 4. A systematic search of the literature for all studies examining the heterogeneity of the ISUP grade group 4 was conducted. Available studies were combined with meta-analysis to evaluate prognostic differences within the ISUP grade group 4 measured by all-cause mortality (ACM) and the prostate cancer-specific mortality (PCSM). Eight studies were identified and utilised a variety of outcome measures to answer the question of heterogeneity within the ISUP grade group 4. Four of these studies examined prognosis using both ACM and PCSM. These were combined into a meta-analysis. The combined group of 5 + 3/3 + 5 had statistically significant higher ACM (hazard ratio [HR] 1.23, 95% confidence internal [Cl] 1.08-1.41) when compared to the 4 + 4 group. There was no difference in the PCSM between the two groups (HR 1.34, 95% CI 0.89-2.01). However, heterogeneity was high for this analysis secondary to a range of methodological differences. Our meta-analysis showed that Gleason grade 3 + 5/5 + 3 had higher ACM than Gleason grade group 4 + 4. Measures of PCSM were statistically insignificant, although heterogeneity was high. Evidence suggests that heterogeneity is likely, although inconclusive. Further studies with consistent methodologies are required to answer this question.

Progressive cranial neuropathy and uterine involvement in myeloid sarcoma.

A rare extramedullary manifestation of haematological malignancy, myeloid sarcoma is most commonly seen in patients with acute myeloid leukaemia. We report on an adult patient who presented with an atypical phenotype of progressive cranial neuropathy without blood or bone marrow involvement, and in whom obtaining material for pathological diagnosis was made challenging by unusual findings of absent fluorodeoxyglucose-positron emission tomography avidity and involvement of sites not readily accessible to biopsy (orbital apex and cauda equina). The eventual diagnosis was obtained through biopsy of the uterine cervix before being verified on repeat lymph node and cerebrospinal fluid sampling prior to initiation of chemotherapy.

Prostate MRI evolution in clinical practice: Audit of tumour detection and staging versus prostatectomy with staged introduction of multiparametric MRI and Prostate Imaging Reporting and Data System v2 reporting.

INTRODUCTION: We conducted a retrospective audit to compare dominant nodule detection and local staging before and after the introduction of functional sequences and PI-RADS v2 reporting to MRI prostate scans in routine private practice. METHODS: A retrospective audit was performed of 245 patients in four separate groups undergoing robotic prostatectomy for prostate cancer by a single urologist between 2009 and 2017. The initial 100 consecutive patients had T2 imaging only. The next 43 patients had T2 and DWI. 52 subsequent patients had T2, DWI and DCE sequences (mpMRI). A final 50 consecutive patients had mpMRI using PI-RADS v2 reporting. Preoperative MRI reports were compared with prostatectomy histopathology to determine the sensitivity of MRI in detecting dominant tumour nodule and T3 extension. RESULTS: The addition of DWI and DCE sequences improved sensitivity for detection of dominant tumour nodule, with a significant further increase using PI-RADS v2 reporting (38% for T2 vs. 62% for T2/DWI vs. 67% for mpMRI vs 91% for PI-RADS v2). The accuracy of detecting T3 disease was initially very low. The use of additional imaging techniques did not significantly influence this, but the use of a three category likelihood of extraprostatic extension in the PI-RADS v2 group had a significant increase in detection of T3 disease (sensitivity 27% vs. 23% vs. 38% vs 63%). CONCLUSION: This audit tracks the significant improvements in MRI detection of prostate cancer dominant tumour nodule and T3 extension in patients undergoing prostatectomy with changing techniques and reporting standards in routine clinical practice.

Extent and predictors of grade upgrading and downgrading in an Australian cohort according to the new prostate cancer grade groupings.

OBJECT: To determine the extent and impact of upgrading and downgrading among men who underwent radical prostatectomy (RP) according to new grade groupings and to identify predictors of upgrading from biopsy grade Group I and II, and downgrading to grade Group I, in a community setting. METHODS: Study participants included 2279 men with non-metastatic prostate cancer diagnosed 2006-2015 who underwent prostatectomy, from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. Extent of up- or down-grading was assessed by comparing biopsy and prostatectomy grade groupings. Risk of biochemical recurrence (BCR) with upgrading was assessed using multivariable competing risk regression. Binomial logistic regression was used to identify pre-treatment predictors of upgrading from grade Groups I and II, and risk group reclassification among men with low risk disease. RESULTS: Upgrading occurred in 35% of cases, while downgrading occurred in 13% of cases. Sixty percent with grade Group I disease were upgraded following prostatectomy. Upgrading from grade Group I was associated with greater risk of BCR compared with concordant grading (Hazard ratio: 3.1, 95% confidence interval: 1.7-6.0). Older age, higher prostate-specific antigen levels (PSA), fewer biopsy cores, higher number of positive cores and more recent diagnosis predicted upgrading from grade Group I, while higher PSA and clinical stage predicted upgrading from grade Group II. No clinical risk factors for reclassification were identified. CONCLUSION: Biopsy sampling errors may play an important role in upgrading from grade Group I. Improved clinical assessment of grade is needed to encourage greater uptake of active surveillance.

ISUP Group 4 - a Homogenous Group of Prostate Cancers?

The International Society of Urological Pathology (ISUP) and the World Health Organisation have adopted a five-tiered prognostic grade group for prostate cancer in 2014. Grade group 4 is comprised of Gleason patterns 4 + 4, 3 + 5 and 5 + 3. Recent articles have suggested heterogeneity in their prognostic outcomes. We aimed to determine whether there was a difference in mortality outcomes within the ISUP 4 grouping, as identified on needle biopsy. A total of 4080 men who were diagnosed with non-metastatic (N0 M0) prostate cancer on biopsy with Gleason scores of 7, 8 and 9 were included. Multi-variable Cox Regression and Fine and Grey competing risk analysis were used to determine the All-Cause Mortality (ACM) and the Prostate Cancer Specific Mortality (PCSM) as a function of Gleason Scores (Gleason 3 + 4, 4 + 3, 4 + 4, 3 + 5/5 + 3, 9). Gleason score 4 + 4 was utilized as the referent. The 60 months' prostate cancer specific mortality with Gleason patterns 4 + 4 and 3 + 5/5 + 3 were 17% and 20% respectively (P < 0.01). Patients with 3 + 5/5 + 3 disease, had no statistically significant difference in the ACM (adjusted hazard ratio [aHR] 0.99, 95% confidence interval [Cl] 0.68-1.4, p = 0.99) and PCSM risk (aHR 0.77, 95% Cl 0.47-1.2, p = 0.31) when compare with the referent group of patients. Patients with Gleason patterns 4 + 3 and 9 had statistically significant difference in their PCSM risk (aHR 0.70, 95% CI 0.54-0.91, P < 0.001 and aHR 1.5, 95% Cl 1.2-1.9, P < 0.001) when compared to the referent group. Our analysis suggest that ISUP group 4 is homogenous in terms of the all-cause mortality and the prostate cancer specific morality risk as differentiated by the presence of Gleason 5 score.

High-grade transitional cell carcinoma masquerading as a xanthogranulomatous pyelonephritis and perinephric abscess.

Xanthogranulomatous pyelonephritis (XGPN) is an atypical long-term pyelonephritis with destruction of renal parenchyma and a long-term inflammatory infiltrate of macrophages. Reported presentations of transitional cell carcinoma (TCC) are different. A 73-year-old woman presented with loin pain, prostration, and fever. Computed tomography scan revealed poor cortical enhancement of the kidney, but some of the images bore resemblance to the characteristic "bear's paw" sign, consistent with XGPN with a 7-cm perinephric collection. She was provisionally diagnosed as severe acute pyelonephritis, possibly XGPN, with abscess. In view of the poor clinical condition, decision was made to perform nephrectomy. Histology revealed a G3pT4 high grade TCC with perineural and vascular invasion and reactive xanthogranulomatous inflammatory response. There are few reports of concomitant XGPN and TCC affecting the kidney. However, there has not been any mention of XGPN and TCC presenting as acute pyelonephritis and perinephric abscess so far.

Comparative biomarker expression and RNA integrity in biospecimens derived from radical retropubic and robot-assisted laparoscopic prostatectomies.

BACKGROUND: Knowledge of preanalytic conditions that biospecimens are subjected to is critically important because novel surgical procedures, tissue sampling, handling, and storage might affect biomarker expression or invalidate tissue samples as analytes for some technologies. METHODS: We investigated differences in RNA quality, gene expression by quantitative real-time PCR, and immunoreactive protein expression of selected prostate cancer biomarkers between tissues from retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic prostatectomy (RALP). Sections of tissue microarray of 23 RALP and 22 RRP samples were stained with antibodies to androgen receptor (AR) and prostate-specific antigen (PSA) as intersite controls, and 14 other candidate biomarkers of research interest to three laboratories within the Australian Prostate Cancer BioResource tissue banking network. Quantitative real-time PCR was done for AR, PSA (KLK3), KLK2, KLK4, and HIF1A on RNA extracted from five RALP and five RRP frozen tissue cores. RESULTS: No histologic differences were observed between RALP and RRP tissue. Biomarker staining grouped these samples into those with increased (PSA, CK8/18, CKHMW, KLK4), decreased (KLK2, KLK14), or no change in expression (AR, ghrelin, Ki67, PCNA, VEGF-C, PAR2, YB1, p63, versican, and chondroitin 0-sulfate) in RALP compared with RRP tissue. No difference in RNA quality or gene expression was detected between RALP and RRP tissue. CONCLUSIONS: Changes in biomarker expression between RALP and RRP tissue exist at the immunoreactive protein level, but the etiology is unclear. IMPACT: Future studies should account for changes in biomarker expression when using RALP tissues, and mixed cohorts of RALP and RRP tissue should be avoided.