ObjectiveTo test the hypothesis that the baseline clinico‐pathological features of the men with localized prostate cancer (PCa) included in the ProtecT (Prostate Testing for Cancer and Treatment) trial who progressed (n = 198) at a 10‐year median follow‐up were different from those of men with stable disease (n = 1409).Patients and MethodsWe stratified the study participants at baseline according to risk of progression using clinical disease stage, pathological grade and PSA level, using Cox proportional hazard models.ResultsThe findings showed that 34% of participants (n = 505) had intermediate‐ or high‐risk PCa, and 66% (n = 973) had low‐risk PCa. Of 198 participants who progressed, 101 (51%) had baseline International Society of Urological Pathology Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5%, respectively, for 1409 participants without progression (P < 0.001). In participants with progression, 38% and 62% had baseline low‐ and intermediate‐/high‐risk disease, compared with 69% and 31% of participants with stable disease (P < 0.001). Treatment received, age (65–69 vs 50–64 years), PSA level, Grade Group, clinical stage, risk group, number of positive cores, tumour length and perineural invasion were associated with time to progression (P ≤ 0.005). Men progressing after surgery (n = 19) were more likely to have a higher Grade Group and pathological stage at surgery, larger tumours, lymph node involvement and positive margins.ConclusionsWe demonstrate that one‐third of the ProtecT cohort consists of people with intermediate‐/high‐risk disease, and the outcomes data at an average of 10 years' follow‐up are generalizable beyond men with low‐risk PCa.

Aims There is increasing evidence of G leason score ( GS ) drift in prostatic core biopsies during the last two decades. The P rotec T study is a randomized controlled study and provides an excellent cohort to study the effect of time, prostate‐specific antigen ( PSA ) level, perineural invasion, tumour length and age on GS . Methods and results The P rotec T study recruited men in the United Kingdom between 1999 and 2010. The Gleason scores were grouped into four categories ≤3 + 3, 3 + 4, 4 + 3 and ≥4 + 4 for analysis. Data from England between 2000 and 2012 were also available. A total of 3282 biopsies containing cancer were analysed. For each year of the ProtecT study, the odds of being diagnosed with a higher GS category increased by 4.9%. Higher GS was also associated with perineural invasion, increasing tumour length, age and PSA level. While biopsy GS from England was incomplete, it also showed a marked decrease in GS five and six tumours during the same period. Conclusion There was GS drift from 3 + 3 to 3 + 4 with time in the ProtecT study, but there appeared to be no significant change in percentage of GS 4 + 3 or higher. This drift was less dramatic when compared to GS in the rest of England.

Testicular germ cell cancer develops from premalignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4+/MAGEA4−) into pre-spermatogonia (OCT4−/MAGEA4+). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesized that cells expressing an immature (OCT4+/MAGEA4−) germ cell profile would exhibit an increased proliferation rate compared with those with a mature profile (OCT4+/MAGEA4+). Therefore, we performed triple immunofluorescence and stereology to quantify the different intratubular germ cell neoplasia cell subpopulations, based on expression of germ cell (OCT4, PLAP, AP2γ, MAGEA4, VASA) and proliferation (Ki67) markers, in testis sections from patients with preinvasive disease, seminoma, and non-seminoma. We compared these subpopulations with normal human fetal testis and with seminoma cells. Heterogeneity of protein expression was demonstrated in intratubular germ cell neoplasia cells with respect to gonocyte and spermatogonial markers. It included an embryonic/fetal germ cell subpopulation lacking expression of the definitive intratubular germ cell neoplasia marker OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation. OCT4+/MAGEA4− cells showed a significantly increased rate of proliferation compared with the OCT4+/MAGEA4+ population (12.8 versus 3.4%, P<0.0001) irrespective of histological tumor type, reflected in the predominance of OCT4+/MAGEA4− cells in the invasive tumor component. Surprisingly, OCT4+/MAGEA4− cells in patients with preinvasive disease showed significantly higher proliferation compared to those with seminoma or non-seminoma (18.1 versus 10.2 versus 7.2%, P<0.05, respectively). In conclusion, this study has demonstrated that OCT4+/MAGEA4− cells are the most frequent and most proliferative cell population in tubules containing intratubular germ cell neoplasia, which appears to be an important factor in determining invasive potential of intratubular germ cell neoplasia to seminomas.

To determine whether the density of CD4 + and CD8 + T-lymphocytes in a transrectal ultrasonography (TRUS) biopsy of the prostate can be used to predict the progression of lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH). In total, 100 patients were randomly selected from a pool of patients with histologically proven, benign TRUS biopsy specimens. There were seven full years of follow-up available. Clinical data were recorded, including prostate volume, International Prostate Symptom Score (IPSS), prostate-specific antigen, urine flow rate, postvoid residual urine volume and previous prostate surgery. Markers of disease progression included the subsequent development of acute urinary retention (AUR), ≥4 point rise in IPSS, prescription of medical therapy (α-blocker or 5-α-reductase inhibitor) and bladder outlet surgery. Four patients’ specimens were unsuitable for analysis. Biopsy sections from 96 patients were immunohistochemically stained for the presence of CD4 + and CD8 + T-lymphocytes and the density of infiltrate was assessed using random field sampling and point counting. Some 29% of patients (28/96) did not have BPH at the time of biopsy. Of all patients, 41% (39/96) progressed, 10% of whom (4/39) did not have BPH at the time of biopsy. A further 10% (10/96) developed AUR, 7% (7/96) had a ≥4 point rise in IPSS, 33% (32/96) required medical therapy for BPH and 11% (11/96) required bladder outlet surgery. There was low correlation between CD4 + and CD8 + densities in paired sections. CD4 + and CD8 + densities did not provide any significant predictive function in the progression of BPH, nor was their any predictive association noted between CD4 + and CD8 + scores and the development of prostate cancer. Sub-analysis did show that a threshold mean of ≥1.35 CD8 + cells per field predicted progression to AUR with a sensitivity of 60% (95% confidence interval, CI, 26.2–87.8), specificity of 73.3% (95% CI 62.6–82.2) but a positive predictive value of 20.6% (95% CI 8.0–39.7). CD4 + infiltrate density suggested a trend to general progression but without statistical significance. The present study, despite certain trends, shows no evidence for an association between CD4 + and CD8 + T-lymphocytes and the progression of LUTS in BPH.

You have accessJournal of UrologyDiscussed Poster, Tuesday, May 24, 2005, 8:00 am - 12:00 pm1 Apr 2005991: Upper Tract Transitional Cell Carcinoma is of Idgher Grade and Stage than Bladder TCC Grant D. Stewart, Simon V. Bariol, Ken M. Grigor, David A. Tolley, and S. Alan McNeill Grant D. StewartGrant D. Stewart More articles by this author , Simon V. BariolSimon V. Bariol More articles by this author , Ken M. GrigorKen M. Grigor More articles by this author , David A. TolleyDavid A. Tolley More articles by this author , and S. Alan McNeillS. Alan McNeill More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)35147-4AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "991: Upper Tract Transitional Cell Carcinoma is of Idgher Grade and Stage than Bladder TCC." The Journal of Urology, 173(4S), p. 268 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 268 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Grant D. Stewart More articles by this author Simon V. Bariol More articles by this author Ken M. Grigor More articles by this author David A. Tolley More articles by this author S. Alan McNeill More articles by this author Expand All Advertisement PDF downloadLoading ...

Transitional cell carcinomas of the urinary bladder are frequently characterised by multiple local recurrences with a low risk of progression. The observation that a significant proportion of patients experience recurrences over many years, even decades, without ever developing aggressive life threatening disease has led to the hypothesis that recurrence is a separate clinical and molecular event in the natural history of this disease. Over recent years a number of studies have been undertaken to test this hypothesis and within the last 12-24 months candidate loci and genes have been identified which may represent such recurrence related molecular events. Within this review we have summarised the data which identifies three key loci on chromosome 9q34, 11q23 and 17q25 as associated with recurrence and sought to place these findings in the context of a multistage molecular model of bladder cancer initiation, recurrence, progression and metastasis. Keywords: bladder cancer, recurrence, progression, molecular genetics, review