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2.
Pathology ; 51(5): 463-473, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279442

RESUMO

The Gleason Grading system has been used for over 50 years to prognosticate and guide the treatment for patients with prostate cancer. At consensus conferences in 2005 and 2014 under the guidance of the International Society of Urological Pathology (ISUP), the system has undergone major modifications to reflect modern diagnostic and therapeutic practices. The 2014 consensus conference yielded recommendations regarding cribriform, mucinous, glomeruloid and intraductal patterns, the most significant of which was the removal of any cribriform pattern from Gleason grade 3. Furthermore, a Gleason score grouping system was endorsed which consisted of five grades where Gleason score 6 (3+3) was classified as grade 1 which better reflected the mostly indolent behaviour of these tumours. Another issue discussed at the meeting and subsequently endorsed was that in Gleason score 7 cases, the percentage pattern 4 should be recorded. This is especially important in situations where modern active surveillance protocols expand to include men with low volume pattern 4. While major progress was made at the conference, several issues were either not resolved or not discussed at all. Most of these items relate to details of assignment of Gleason score and ISUP grade in specific specimen types and grading scenarios. This detailed review looks at the 2014 ISUP conference results and subsequent literature from an international perspective and proposes several recommendations. The specific issues addressed are percentage pattern 4 in Gleason score 7 tumours, percentage patterns 4 and 5 or 4/5 in Gleason score 8-10 disease, minor (≤5%) high grade patterns when either 2 or 3 patterns are present, level of reporting (core, specimen, case), dealing with grade diversity among site (highest and composite scores) and reporting scores in radical prostatectomy specimens with multifocal disease. It is recognised that for many of these issues, a strong evidence base does not exist, and further research studies are required. The proposed recommendations mostly reflect consolidated expert opinion and they are classified as established if there was prior agreement by consensus and provisional if there was no previous agreement or if the item was not discussed at prior consensus conferences. For some items there are reporting options that reflect the local requirements and diverse practice models of the international urological pathology community. The proposed recommendations provide a framework for discussion at future consensus meetings.

3.
J Clin Pathol ; 72(9): 573-578, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31300532

RESUMO

The International Collaboration on Cancer Reporting (ICCR) has developed a suite of detailed datasets for international implementation. These datasets are based on the reporting protocols developed by the Royal College of Pathologists (UK), The Royal College of Pathologists of Australasia and the College of American Pathologists, with modifications undertaken by international expert groups appointed according to ICCR protocols. The dataset for the reporting of renal biopsy for tumour is designed to provide a structured reporting template containing minimum data recording key elements suitable for international use. In formulating the dataset, the ICCR panel incorporated recommendations from the 2012 Vancouver Consensus Conference of the International Society of Urological Pathology (ISUP) and the 2016 edition of the WHO Bluebook on tumours of the urinary and male genital systems. Reporting elements were divided into Required (Core) and Recommended (Non-core) components of the report. Required elements are as follows: specimen laterality, histological tumour type, WHO/ISUP histological tumour grade, sarcomatoid morphology, rhabdoid morphology, necrosis, lymphovascular invasion and coexisting pathology in non-neoplastic kidney. Recommended reporting elements are as follows: operative procedure, tumour site(s), histological tumour subtype and details of ancillary studies. In particular, it is noted that fluorescence in situ hybridisation studies may assist in diagnosing translocation renal cell carcinoma (RCC) and in distinguishing oncocytoma and eosinophilic chromophobe RCC. It is anticipated that the implementation of this dataset into routine clinical practice will facilitate uniformity of pathology reporting worldwide. This, in turn, should have a positive impact on patient treatment and the quality of demographic information held by cancer registries.


Assuntos
Biópsia/normas , Confiabilidade dos Dados , Bases de Dados Factuais/normas , Conjuntos de Dados como Assunto/normas , Cooperação Internacional , Neoplasias Renais/patologia , Consenso , Comportamento Cooperativo , Guias como Assunto/normas , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/cirurgia , Gradação de Tumores/normas , Nefrectomia/normas , Valor Preditivo dos Testes
4.
Am J Surg Pathol ; 43(10): e1-e12, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31192862

RESUMO

Cancer reporting guidelines have been developed and utilized in many countries throughout the world. The International Collaboration on Cancer Reporting (ICCR), through an alliance of colleges and other pathology organizations in Australasia, United Kingdom, Ireland, Europe, USA, and Canada, has developed comprehensive standardized data sets to provide for global usage and promote uniformity in cancer reporting. Structured reporting facilitates provision of all necessary information, which ensures accurate and comprehensive data collection, with the ultimate aim of improving cancer diagnostics and treatment. The data set for primary carcinoma of the renal pelvis and ureter treated with nephroureterectomy or ureterectomy had input from an expert panel of international uropathologists. This data set was based on current evidence-based practice and incorporated information from the 2016 fourth edition of the World Health Organization (WHO) Bluebook on tumors of the urinary and male genital systems and the 2017 American Joint Committee on Cancer (AJCC) TNM staging eighth edition. This protocol applies to both noninvasive and invasive carcinomas in these locations. Reporting elements are considered to be essential (required) or nonessential (recommended). Required elements include operative procedure, specimens submitted, tumor location, focality and size, histologic tumor type, subtype/variant of urothelial carcinoma, WHO grade, extent of invasion, presence or absence of vascular invasion, status of the resection margins and lymph nodes and pathologic stage. The data set provides a detailed template for the collection of data and it is anticipated that this will facilitate appropriate patient management with the potential to foster collaborative research internationally.

5.
Am J Surg Pathol ; 43(9): 1249-1252, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31219816

RESUMO

This study was undertaken to determine the association between extrarenal tumor spread and size in a series of well-sampled clear cell renal cell carcinoma (ccRCC). In a series of 917 cases of ccRCC, 178 were >7 cm in maximum extent. Assessment of tumors >7 cm in size showed 72 (40.4%) to have renal sinus infiltration, the tumor infiltrating perirenal fat in 7 (3.9%) cases, and both in 96 (53.9%) cases. In the remaining 3 (1.7%) cases, no extrarenal extension of the tumor was seen. These 3 cases with organ-confined ccRCC were all cystic tumors. Two showed extensive infarction with associated hemorrhage and the presence of a thick investing pseudocapsule, while the third was a cystic ccRCC arising in the upper pole of the kidney. For the ccRCCs in the series that were ≤7 cm in maximum extent, division of cases according to tumor size and pT staging category showed an increase in the proportion of tumors showing extrarenal spread with increasing size, ranging from 0% for tumors <1 cm in diameter to 84.7% for tumors >6 to 7 cm. The study has shown that for ccRCC, the extrarenal spread of tumor is strongly associated with the size of the primary tumor. The study has also shown that renal sinus invasion and/or perirenal fat infiltration by tumor is commonplace in tumors >7 cm in maximum extent and that tumors of this dimension are rarely organ-confined. These findings provide evidence that the defining features of pT1, pT2, and pT3a staging categories for ccRCC require revision.

6.
Virchows Arch ; 475(3): 263-277, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31098802

RESUMO

The International Collaboration on Cancer Reporting (ICCR) was formed in 2011 to harmonise the datasets, protocols and checklists for pathological reporting of various cancers and develop internationally agreed upon, evidence-based datasets. A dataset for prostate cancer in radical prostatectomy specimens was developed in 2011-2012 as part of a pilot project; however, it required substantial revision following the ISUP Consensus Conference on Gleason Grading in 2014, the publication of the World Health Organisation (WHO) Classification of Tumours of the Urinary System and Male Genital Organs in 2016, and the 8th edition of the Tumour-Node-Metastasis (TNM) staging system in late 2016. This article presents the up-to-date, evidence-based ICCR dataset and associated commentary for reporting prostate cancer in radical prostatectomy specimens. PubMed and Google search engines were used to review the published literature on the subject, and the dataset was developed in line with the previously published ICCR framework for the development of cancer datasets. Substantial changes have been incorporated into the second edition of the ICCR prostate cancer (radical prostatectomy) dataset. These include revisions to prostate cancer grading, reporting of intraductal carcinoma of prostate and surgical margins, among others. Up-to-date cancer datasets underpin structured reporting and facilitate the production of consistent and accurate pathological data for patient care as well as comparisons between different cohorts and populations internationally.


Assuntos
Patologia Clínica/normas , Neoplasias da Próstata/classificação , Consenso , Bases de Dados Factuais/normas , Humanos , Masculino , Gradação de Tumores , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/fisiopatologia
7.
APMIS ; 127(8): 554-560, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31127651

RESUMO

This study aimed to investigate the expression of programmed death receptor ligand 1 (PD-L1) and deficient mismatch repair (dMMR) in ductal adenocarcinoma of the prostate. A tissue microarray of 32 ductal and 42 grade-matched acinar adenocarcinomas was used. Slides were stained for PD-L1, PD-L2, MMR proteins, CD4 and CD8. PD-L1 expression in tumor cells was only seen in 3% (1/34) of ductal and 5% (2/42) of acinar adenocarcinomas (p = 1.0), while PD-L1 expression in tumor-infiltrating immune cells was seen in 29% (10/34) of ductal and 14% (6/42) of acinar adenocarcinomas (p = 0.16). dMMR, as defined by loss of one or more of the MMR proteins, was identified in 5% (4/73) of cases, including 1 ductal and 3 acinar adenocarcinomas. There was a suggested association between infiltration of CD8+ lymphocytes and ductal subtype (p = 0.04) but not between CD4+ lymphocytes and tumor type (p = 0.28). The study shows that both dMMR and PD-L1 expression is uncommon in tumor cells of both ductal and acinar adenocarcinoma of the prostate, while PD-L1 expression in tumor-infiltrating immune cells is a more common finding.


Assuntos
Antígeno B7-H1/imunologia , Carcinoma Ductal/genética , Reparo de Erro de Pareamento de DNA , Neoplasias da Próstata/genética , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Carcinoma Ductal/patologia , Humanos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Instabilidade de Microssatélites , Neoplasias da Próstata/patologia , Análise Serial de Tecidos , Microambiente Tumoral
8.
Eur Urol ; 76(4): 413-415, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31080126

RESUMO

The clinical utility of the World Health Organisation 1973 and 2004 systems for grading bladder cancer are limited by inclusion of biologically heterogeneous categories of grade 2 and high grade, respectively. Reporting both systems in parallel would improve risk stratification by splitting these categories.

9.
Pathology ; 51(4): 349-352, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30987774

RESUMO

Heterogeneity of tumour grading is common in clear cell renal cell carcinoma (ccRCC). WHO/ISUP grading specifies that RCC should be graded based on the highest grade present in at least one high power field. This does not take into account the proportion of high grade tumour present in a cancer, which may itself influence outcome. Cases of ccRCC accessioned by Aquesta Uropathology, Brisbane, Australia, between 2008 and 2015, were reviewed and grading assigned according to WHO/ISUP criteria. For tumours classified as grade 3 (G3) and 4 (G4), the percentage of tumour showing G3 and G4 morphology was assessed for each case. Survival analysis, with time to the development of metastases as the clinical outcome, was performed for six grading subclasses (G3 <10%, G3 10-50%, G3 >50%, G4 <10%, G4 10-50%, G4 >50%). Of the 681 cases of ccRCC in the series, there were 153 cases classified as G3 (91 cases) and G4 (62 cases) for which follow-up was available. During the follow-up period of <1-89 months, 19 (20.9%) patients with G3 and 30 (48.3%) patients with G4 cancers developed metastatic disease. The three subgroups of <10%, 10-50% and >50% G3 tumour were not significant in predicting outcome (p=0.47). Separating G3 into two groups of ≤50% vs >50% was also not significantly associated with outcome (p=0.22). For the three subgroups of G4 ccRCC (<10%, 10-50% and >50% G4) a higher percentage of G4 correlated with time to the development of metastases (p=0.01). Even though G4 tumours as a whole had a significantly worse outcome than G3 tumours (p=0.0004), the difference between G4 <10% and G3 tumours was not significant (p=0.27). On multivariate analysis, that included pT staging category and tumour size, there was a significant difference in survival between G4<10% and G4>50% tumours (p=0.018). The results of the study suggest that for ccRCC, WHO/ISUP G4 category should incorporate the percentage of G4 tumour present.

10.
Histopathology ; 75(4): 453-467, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31009090

RESUMO

The International Collaboration on Cancer Reporting (ICCR) is a not-for-profit organisation sponsored by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Association of Pathologists in association with the Canadian Partnership Against Cancer, the European Society of Pathology, the American Society of Clinical Pathology and the Faculty of Pathology, Royal College of Physicians of Ireland. Its goal is to produce standardised, internationally agreed-upon, evidence-based datasets for cancer pathology reporting throughout the world. This paper describes the development of a cancer dataset by the multidisciplinary ICCR expert panel for the reporting of carcinoma of the urethra in urethrectomy specimens. The dataset is composed of 'required' (mandatory) and 'recommended' (non-mandatory) elements, which are based on a review of the most recent evidence and supported by explanatory commentary. Fourteen required elements and eight recommended elements were agreed by the international dataset authoring committee to represent the essential/required (core) and recommended (non-core) information for the reporting of carcinoma of the urethra in urethrectomy specimens. Use of an internationally agreed, structured pathology dataset for reporting carcinoma of the urethra (in urethrectomy specimens) will provide the necessary information for optimal patient management, will facilitate consistent data collection and will provide valuable data for research and international benchmarking. The dataset will be valuable for those countries and institutions that are not in a position to develop their own datasets.

11.
Virchows Arch ; 474(5): 525-534, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30825003

RESUMO

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.


Assuntos
Adenocarcinoma/patologia , Carcinoma Intraductal não Infiltrante/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Adenocarcinoma/diagnóstico , Biópsia por Agulha , Carcinoma Intraductal não Infiltrante/diagnóstico , Humanos , Masculino , Gradação de Tumores/métodos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico
12.
Prostate ; 79(8): 920-928, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30908670

RESUMO

BACKGROUND: The majority of clinical prostate cancers are multifocal with morphological and molecular heterogeneity. Adequate tissue representation is crucial for the clinical utility of multigene panel sequencing of core needle biopsies. The aim of this study was to evaluate the genomic heterogeneity in multifocal prostate cancer and to analyze how representative preoperative biopsies are of spatially separated tumor foci. METHODS: We analyzed at least 2 tumor foci and 1 to 3 preoperative biopsy cores from 11 patients. Diagnostic biopsies, as well as fresh frozen and formalin-fixed paraffin-embedded samples, from major tumor foci of radical prostatectomy specimens were macrodissected for the enrichment of tumor tissue. DNA was extracted and sequenced. We analyzed structural alterations, mutations, and copy number variations and compared the genomic profiles of tumor foci with those of preoperative biopsies. RESULTS: Alterations were rarely shared between foci, indicating a high degree of genomic heterogeneity. In 8 of 11 men at least 1 tumor focus was represented by the biopsies defined as harboring at least 1 common clonal somatic event. In only one case, somatic alterations from two spatially separate tumors were identified in the biopsies. Of the mutations and structural variants detected in fresh frozen or formalin-fixed paraffin-embedded prostatectomy material, only an average of 19% (range 0-44) and 55% (range 0-100), respectively, were found in preoperative biopsies where a common somatic origin was established. CONCLUSIONS: Multifocal prostate cancer is a somatically heterogeneous disease in which systematic needle biopsies do not provide sufficient molecular representation of the somatic alterations detected in spatially distinct tumor areas. Targeted biopsies, directed at separate tumor foci, could potentially improve tissue representation of these heterogeneous foci in preoperative biopsies.

13.
Virchows Arch ; 474(5): 577-584, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30790058

RESUMO

Pathology training resources remain scarce in many parts of the world. With rapid economic development comes the need to educate new pathologists to meet the medical care demands. Our aim was to set up a cost-effective system for training and testing the diagnostic skills of pathologists. Pathologists in nine countries in Asia and South America were invited by the International Society of Urological Pathology (ISUP) to participate in a prostate pathology education course combining image-based tests with lectures and on-line tutorials. The tests and tutorials are available free of charge at the ISUP education website www.edu.isupweb.org . A total of 603 pathologists registered on the website. Of these, 224 completed pre- and post-lecture assessments (tests 1 and 2). Replies were classified as correct/acceptable, when a lesion was accurately classified into clinically relevant categories (benign, cancer, high-grade prostatic intraepithelial neoplasia, intraductal carcinoma of the prostate). The rate of correct/acceptable replies increased from 60.7 to 72.3% in Tests 1 and 2, respectively. In Test 1, pathologists from upper middle, lower middle, and low resource countries gave a correct/acceptable diagnosis in 65.8%, 61.0%, and 47.4%, respectively. Their results improved in Test 2 to 76.4%, 72.5%, and 62.8%, respectively. The greatest improvement in diagnostic ability was achieved in pathologists from the low resource group of countries. The use of web-based testing and training, combined with lectures, is an efficient method for improving diagnostic skills of pathologists in low to middle resource countries.


Assuntos
Carcinoma Intraductal não Infiltrante/patologia , Patologistas/educação , Próstata/patologia , Neoplasias da Próstata/patologia , Humanos , Internet , Masculino , Gradação de Tumores , Neoplasias da Próstata/diagnóstico
14.
Pathol Int ; 69(2): 55-66, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30694570

RESUMO

Histological grading of prostate cancer is one of the most important tissue-based parameters for prediction of outcome and treatment response. Gleason grading remains the foundation of prostate cancer grading, but has undergone a series of changes in the past 30 years, often initiated by consensus conference decisions. This review summarizes the most important modifications that were introduced by the 2005 and 2014 International Society of Urological Pathology (ISUP) revisions of Gleason grading and discusses the impact that these have had on current grading practices. A considerable inflation in Gleason scores has been observed, especially following the ISUP 2005 revision, and the effects of this are discussed. ISUP 2014 grading recommendations are described, including the reporting of ISUP grades 1-5. Controversial issues include methods for reporting of grades on needle biopsies, reporting of percent Gleason grades 4/5 and grading of cribriform and intraductal carcinoma of the prostate. Educational programs developed recently to promote standardization of grading are described and their results assessed.


Assuntos
Gradação de Tumores/métodos , Gradação de Tumores/normas , Neoplasias da Próstata/patologia , Humanos , Masculino
15.
J Urol ; 201(4): 815-820, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30672842

RESUMO

PURPOSE: The majority of men who undergo pelvic lymph node dissection at radical prostatectomy have benign lymph node histology. The aim of this study was to assess the predictive value of preoperative 68Ga-PSMA (prostate specific membrane antigen) positron emission tomography/computerized tomography to predict histological metastasis on pelvic lymph node dissection performed during radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the sensitivity, specificity, and positive and negative predictive values of preoperative staging 68Ga-PSMA positron emission tomography/computerized tomography to identify histological lymph node metastasis in 208 consecutive men who subsequently proceeded with pelvic lymph node dissection at radical prostatectomy. RESULTS: Median prostate specific antigen was 7.6 µg/l, the lymph node count was 13 and Gleason score was 4 + 5. On a per patient basis only 21 of the 55 men with metastasis on histological examination were identified on 68Ga-PSMA positron emission tomography/computerized tomography for 38.2% sensitivity. Of the 143 men with no lymph node metastasis on 68Ga-PSMA imaging 34 had metastasis on histology for 80.8% negative predictive value. Specificity was 93.5% and positive predictive value was 67.7%. For the 172 histologically identified malignant lymph node metastases the sensitivity per node was 24.4% and specificity was 99.5%. CONCLUSIONS: If negative 68Ga-PSMA positron emission tomography/computerized tomography is used as the basis of not performing pelvic lymph node dissection, 80% of men would avoid unnecessary pelvic lymph node dissection. However, 68Ga-PSMA positron emission tomography/computerized tomography has poor sensitivity per node to detect all histologically positive lymph node metastases. Thus, pelvic lymph node dissection remains the gold standard to stage pelvic lymph nodes despite its known limitations and complications.


Assuntos
Ácido Edético/análogos & derivados , Linfonodos/patologia , Oligopeptídeos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Biópsia por Agulha , Estudos de Coortes , Humanos , Imuno-Histoquímica/métodos , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Intensificação de Imagem Radiográfica , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
16.
Lancet Oncol ; 20(2): 267-281, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30579763

RESUMO

BACKGROUND: The optimal duration of androgen suppression for men with locally advanced prostate cancer receiving radiotherapy with curative intent is yet to be defined. Zoledronic acid is effective in preventing androgen suppression-induced bone loss, but its role in preventing castration-sensitive bone metastases in locally advanced prostate cancer is unclear. The RADAR trial assessed whether the addition of 12 months of adjuvant androgen suppression, 18 months of zoledronic acid, or both, can improve outcomes in men with locally advanced prostate cancer who receive 6 months of androgen suppression and prostatic radiotherapy. This report presents 10-year outcomes from this trial. METHODS: For this randomised, phase 3, 2 × 2 factorial trial, eligible men were 18 years or older with locally advanced prostate cancer (either T2b-4, N0 M0 tumours or T2a, N0 M0 tumours provided Gleason score was ≥7 and baseline prostate-specific antigen [PSA] concentration was ≥10 µg/L). We randomly allocated participants in a 2 × 2 factorial design by computer-generated randomisation (using the minimisation technique, and stratified by centre, baseline PSA concentration, clinical tumour stage, Gleason score, and use of a brachytherapy boost) in a 1:1:1:1 ratio to four treatment groups. Patients in the control group received 6 months of neoadjuvant androgen suppression with leuprorelin (22·5 mg every 3 months, intramuscularly) and radiotherapy alone (short-term androgen suppression [STAS]); this treatment was either followed by another 12 months of adjuvant androgen suppression with leuprorelin (22·5 mg every 3 months, intramuscularly; intermediate-term androgen suppression [ITAS]), or accompanied by 18 months of zoledronic acid (4 mg every 3 months, intravenously) starting at randomisation (STAS plus zoledronic acid), or both (ITAS plus zoledronic acid). All patients received radiotherapy to the prostate and seminal vesicles, starting from the end of the fifth month of androgen suppression; dosing options were 66, 70, and 74 Gy in 2-Gy fractions per day, or 46 Gy in 2-Gy fractions followed by a high-dose-rate brachytherapy boost dose of 19·5 Gy in 6·5-Gy fractions. Treatment allocation was open label. The primary endpoint was prostate cancer-specific mortality and was analysed according to intention-to-treat using competing-risks methods. The trial is closed to follow-up and this is the final report of the main endpoints. This trial is registered with ClinicalTrials.gov, number NCT00193856. FINDINGS: Between Oct 20, 2003, and Aug 15, 2007, 1071 men were enrolled and randomly assigned to STAS (n=268), ITAS (n=268), STAS plus zoledronic acid (n=268), and ITAS plus zoledronic acid (n=267). Median follow-up was 10·4 years (IQR 7·9-11·7). At this 10-year follow-up, no interactions were observed between androgen suppression and zoledronic acid so the treatment groups were collapsed to compare treatments according to duration of androgen suppression: 6 months of androgen suppression plus radiotherapy (6AS+RT) versus 18 months of androgen suppression plus radiotherapy (18AS+RT) and to compare treatments according to whether or not patients received zoledronic acid. The total number of deaths was 375 (200 men receiving 6AS+RT and 175 men receiving 18AS+RT), of which 143 (38%) were attributable to prostate cancer (81 men receiving 6AS+RT and 62 men receiving 18AS+RT). When analysed by duration of androgen suppression, the adjusted cumulative incidence of prostate cancer-specific mortality was 13·3% (95% CI 10·3-16·0) for 6AS+RT versus 9·7% (7·3-12·0) for 18AS+RT, representing an absolute difference of 3·7% (95% CI 0·3-7·1; sub-hazard ratio [sHR] 0·70 [95% CI 0·50-0·98], adjusted p=0·035). The addition of zoledronic acid did not affect prostate cancer-specific mortality; the adjusted cumulative incidence of prostate cancer-specific mortality was 11·2% (95% CI 8·7-13·7) with zoledronic acid vs 11·7% (9·2-14·1) without, representing an absolute difference of -0·5% (95% CI -3·8 to 2·9; sHR 0·95 [95% CI 0·69-1·32], adjusted p=0·78). Although safety analysis was not prespecified for this 10-year analysis, one new serious adverse event (osteonecrosis of the mandible, in a patient who received 18 months of androgen suppression plus zoledronic acid) occurred since our previous report, bringing the total number of cases of this serious adverse event to three (<1% out of 530 patients who received zoledronic acid evaluated for safety) and the total number of drug-related serious adverse events to 12 (1% out of all 1065 patients evaluable for safety). No treatment-related deaths occurred during the study. INTERPRETATION: 18 months of androgen suppression plus radiotherapy is a more effective treatment option for locally advanced prostate cancer than 6 months of androgen suppression plus radiotherapy, but the addition of zoledronic acid to this treatment regimen is not beneficial. Evidence from the RADAR and French Canadian Prostate Cancer Study IV trials suggests that 18 months of androgen suppression with moderate radiation dose escalation is an effective but more tolerable option than longer durations of androgen suppression for men with locally advanced prostate cancer including intermediate and high risk elements. FUNDING: National Health and Medical Research Council of Australia, Novartis Pharmaceuticals Australia, AbbVie Pharmaceuticals Australia, New Zealand Health Research Council, New Zealand Cancer Society, Cancer Standards Institute New Zealand, University of Newcastle (Australia), Hunter Medical Research Institute, Calvary Mater Newcastle Radiation Oncology Fund, and Maitland Cancer Appeal.

17.
Histopathology ; 74(1): 4-17, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30565310

RESUMO

Grading of renal cell carcinoma (RCC) has been recognised as a prognostic factor for almost 100 years. Numerous grading systems have been proposed, initially focusing upon a constellation of cytological features and more recently on nuclear morphology. It has been recommended that grading of RCC should be based upon nucleolar prominence/eosinophilia for grades 1-3, while grade 4 requires nuclear anaplasia (including tumour giant cells, sarcomatoid differentiation and/or rhabdoid morphology). The grading system was adopted formally by the International Society of Urological Pathology (ISUP) and subsequently by the World Health Organisation (WHO), being designated the WHO/ISUP grading classification in the fourth edition of the WHO classification tumours of the urinary system and male genital organs (2016). This grading system has been validated for both clear cell and papillary RCC. Validation studies for chromophobe RCC failed to demonstrate a correlation between grade and outcome for both the superseded Fuhrman grading system and the WHO/ISUP grading classification, and it has been recommended that these tumours not be graded. The WHO/ISUP system has been incorporated into the structured reports of the International Cancer Collaboration on Cancer Reporting for both clear cell and papillary RCC. It is also noted that other types of RCC may be graded, but it must be emphasised in the report that this is for descriptive and diagnostic purposes, and not outcome prediction. More recent studies have shown the incorporation of the presence of tumour necrosis into RCC grading to improve outcome prediction, and this has been validated in several studies.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Gradação de Tumores/métodos , Humanos
20.
Pathology ; 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30477882

RESUMO

The International Collaboration on Cancer Reporting (ICCR) is a project which issues datasets and guidelines for international standardisation of cancer reporting. This review summarises the required and recommended elements of the datasets for prostate core needle biopsies and transurethral resection (TURP) and enucleation specimens of the prostate. To obtain as much information as possible from needle biopsies there should be only one core in each specimen jar with the exception of saturation biopsies. The gross description of the specimens should include core lengths of needle biopsies and weight of resection specimens. The tumours should be classified according to the 4th World Health Organization (WHO) classification and graded both by Gleason scores and the grouping of these in International Society of Urological Pathology (ISUP) grades (Grade groups). Percent high-grade cancer is an optional component of the report. Tumour extent in needle biopsies should be reported both by number of cores positive for cancer and the linear extent measured in either millimetre or percent core involvement by tumour. In needle biopsies where low-grade cancer is discontinuous and seen in few cores, it is recommended that the tumour extent should be reported both by including and subtracting intervening benign tissue. For resection specimens, the percentage of the tissue area (or percentage of number of TURP chips) involved with cancer should be estimated. Extraprostatic extension should be reported when seen, while the reporting of perineural, seminal vesicle/ejaculatory duct and lymphovascular invasion is only recommended. Intraductal carcinoma of the prostate (IDC-P) should be reported when present, because of its strong link with aggressive cancer. The current recommendation is that the IDC-P component should not be graded. The structured and standardised reporting of prostate cancer contributes to safer and more efficient patient care and facilitates the compilation and understanding of multiparametric diagnostic and prognostic data.

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