Head to head: should the intraductal component of invasive prostate cancer be graded?

The reporting of intraductal carcinoma of the prostate (IDCP) is controversial, with conflicting recommendations having recently been published by the International Society of Urological Pathology (ISUP) and the Genitourinary Pathology Society (GUPS). Both recommend that isolated (pure) IDCP should not be graded. However, the ISUP recommends incorporating the IDCP component of invasive prostate cancer in the Gleason score, whereas the GUPS recommends reporting IDCP as a comment, independently of the Gleason score. The arguments for and against incorporating the IDCP component of invasive prostate cancer in the Gleason score are discussed in detail

Effect of Fibres on the behaviour of Bottle shaped strut

Bottle-shaped struts are the critical elements in the design of D-regions using Strut- and-Tie method. The transverse tension develops due to dispersion of compression load which further leads to splitting crack in bottle shaped strut. Due to this, the strut fails before reaching its ultimate compression capacity. Higher resistance to the transverse tension can improve the strut capacity and its efficiency in load transfer. Transverse tensile stress can be resisted by providing the steel reinforcement or through the addition of discrete fibres in the concrete. Many international codes like ACI, AASTHO, and CSA have suggested guidelines about the addition of steel fibre reinforcement in the bottle-shaped struts for resisting the transverse tension. Still, the influence of the discrete fibres on the performance of the bottle-shaped strut is not well established. The performance of the bottle-shaped strut in terms of efficiency factors, crack pattern and failure mode for different amounts of macro steel fibres and micro polypropylene fibres are studied using experimental investigation. Specimens of 600mm x 600mmx 100mm size were tested under compression. Steel fibres are added in the proportions of 0.7%, 0.9% and 1.1% volume fractions to the concrete. Effect of fibre hybridization also studied by adding micro polypropylene fibres in the proportions of 1% and 2% in addition to the steel fibres. Experimental results showed that adding discrete fibres in concrete significantly improved the resistance to the transverse tension in bottle-shaped struts and led to the increased load-carrying capacity of the specimens. A 75% improvement in the efficiency factor is observed at 0.9% volume of steel fibre addition. Addition of micro polypropylene fibres to the macro steel fibres further enhanced the load-carrying capacity of the bottle-shaped struts. Microfibres in the concrete effectively arrested the micro-cracks and delayed the occurrence of a first splitting crack in the strut region. Due to this the mode of failure changed to ductile through the formation of a greater number of small cracks with less crack width at the ultimate load. Results of this study clearly show that the addition of discrete fibres to the concrete is an effective solution to improve the performance of the bottle-shaped struts in terms of ultimate strength and serviceability. © 2021 Institute of Physics Publishing

Intraductal carcinoma of the prostate: a critical re-appraisal

Intraductal carcinoma of the prostate gland (IDCP), which is now categorised as a distinct entity by WHO 2016, includes two biologically distinct diseases. IDCP associated with invasive carcinoma (IDCP-inv) generally represents a growth pattern of invasive prostatic adenocarcinoma while the rarely encountered pure IDCP is a precursor of prostate cancer. This review highlights issues that require further discussion and clarification. The diagnostic criterion “nuclear size at least 6 times normal” is ambiguous as “size” could refer to either nuclear area or diameter. If area, then this criterion could be re-defined as nuclear diameter at least three times normal as it is difficult to visually compare area of nuclei. It is also unclear whether IDCP could also include tumours with ductal morphology. There is no consensus whether pure IDCP in needle biopsies should be managed with re-biopsy or radical therapy. A pragmatic approach would be to recommend radical therapy only for extensive pure IDCP that is morphologically unequivocal for high-grade prostate cancer. Active surveillance is not appropriate when low-grade invasive cancer is associated with IDCP, as such patients usually have unsampled high-grade prostatic adenocarcinoma. It is generally recommended that IDCP component of IDCP-inv should be included in tumour extent but not grade. However, there are good arguments in favour of grading IDCP associated with invasive cancer. All historical as well as contemporary Gleason outcome data are based on morphology and would have included an associated IDCP component in the tumour grade. WHO 2016 recommends that IDCP should not be graded, but it is unclear whether this applies to both pure IDCP and IDCP-inv

Pathological upgrading in prostate cancer treated with surgery in the United Kingdom: trends and risk factors from the British Association of Urological Surgeons Radical Prostatectomy Registry

Background Accurate grading at the time of diagnosis if fundamental to risk stratification and treatment decision making in patients with prostate cancer. Whilst previous studies have demonstrated significant pathological upgrading and downgrading following radical prostatectomy (RP), these were based on historical cohorts and do not reflect contemporary patient selection and management practices. The aim of this national, multicentre observational study was to characterise contemporary rates and risk factors for pathological upgrading after RP in the United Kingdom (UK). Methods All RP entries on the British Association of Urological Surgeons (BAUS) Radical Prostatectomy Registry database of prospectively entered cases undertaken between January 2011 and December 2016 were extracted. Those patients with full preoperative PSA, clinical stage, needle biopsy and subsequent RP pathological grade information were included. Upgrade was defined as any increase in Gleason grade from initial needle biopsy to pathological assessment of the entire surgical specimen. Statistical analysis and multivariate logistic regression were undertaken using R version 3.5 (R Foundation for Statistical Computing, Vienna, Austria). Results A total of 17,598 patients met full inclusion criteria. Absolute concordance between initial biopsy and pathological grade was 58.9% (n = 10,364), whilst upgrade and downgrade rates were 25.5% (n = 4489) and 15.6% (n = 2745) respectively. Upgrade rate was highest in those with D’Amico low risk compared with intermediate and high-risk disease (55.7% versus 19.1 and 24.3% respectively, P < 0.001). Although rates varied between year of surgery and geographical regions, these differences were not significant after adjusting for other preoperative diagnostic variables using multivariate logistic regression. Conclusions Pathological upgrading after RP in the UK is lower than expected when compared with other large contemporary series, despite operating on a generally higher risk patient cohort. As new diagnostic techniques that may reduce rates of pathological upgrading become more widely utilised, this study provides an important benchmark against which to measure future performance

Gleason Grade 4 Prostate Adenocarcinoma Patterns: An Inter-observer Agreement Study among Genitourinary Pathologists

Aims To assess the interobserver reproducibility of individual Gleason grade 4 growth patterns. Methods and results Twenty-three genitourinary pathologists participated in the evaluation of 60 selected high-magnification photographs. The selection included 10 cases of Gleason grade 3, 40 of Gleason grade 4 (10 per growth pattern), and 10 of Gleason grade 5. Participants were asked to select a single predominant Gleason grade per case (3, 4, or 5), and to indicate the predominant Gleason grade 4 growth pattern, if present. ‘Consensus’ was defined as at least 80% agreement, and ‘favoured’ as 60–80% agreement. Consensus on Gleason grading was reached in 47 of 60 (78%) cases, 35 of which were assigned to grade 4. In the 13 non-consensus cases, ill-formed (6/13, 46%) and fused (7/13, 54%) patterns were involved in the disagreement. Among the 20 cases where at least one pathologist assigned the ill-formed growth pattern, none (0%, 0/20) reached consensus. Consensus for fused, cribriform and glomeruloid glands was reached in 2%, 23% and 38% of cases, respectively. In nine of 35 (26%) consensus Gleason grade 4 cases, participants disagreed on the growth pattern. Six of these were characterized by large epithelial proliferations with delicate intervening fibrovascular cores, which were alternatively given the designation fused or cribriform growth pattern (‘complex fused’). Conclusions Consensus on Gleason grade 4 growth pattern was predominantly reached on cribriform and glomeruloid patterns, but rarely on ill-formed and fused glands. The complex fused glands seem to constitute a borderline pattern of unknown prognostic significance on which a consensus could not be reached

The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma

Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging-targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed

Utility of Pathology Imagebase for Standardization of Prostate Cancer Grading

Aims: Despite efforts to standardise grading of prostate cancer, even among experts there is still a considerable variation in grading practices. In this study we describe the use of Pathology Imagebase, a novel reference image library, for setting an international standard in prostate cancer grading. Methods and results: The International Society of Urological Pathology (ISUP) recently launched a reference image database supervised by experts. A panel of 24 international experts in prostate pathology reviewed independently microphotographs of 90 cases of prostate needle biopsies with cancer. A linear weighted kappa of 0.67 (95% confidence interval = 0.62-0.72) and consensus was reached in 50 cases. The interobserver weighted kappa varied from 0.48 to 0.89. The highest level of agreement was seen for Gleason score (GS) 3 + 3 = 6 (ISUP grade 1), while higher grades and particularly GS 4 + 3 = 7 (ISUP grade 3) showed considerable disagreement. Once a two-thirds majority was reached, images were moved automatically into a public database available for all ISUP members at www.isupweb.org. Non-members are able to access a limited number of cases. Conclusions: It is anticipated that the database will assist pathologists to calibrate their grading and, hence, decrease interobserver variability. It will also help to identify instances where definitions of grades need to be clarified

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Reporting trends, practices, and resource utilization in neuroendocrine tumors of the prostate gland: a survey among thirty-nine genitourinary pathologists

Background: Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods: Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results: A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion: There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland