Significant Inter- and Intralaboratory Variation in Gleason Grading of Prostate Cancer: A Nationwide Study of 35,258 Patients in The Netherlands

Purpose: Our aim was to analyze grading variation between pathology laboratories and between pathologists within individual laboratories using nationwide real-life data. Methods: We retrieved synoptic (n = 13,397) and narrative (n = 29,377) needle biopsy reports from the Dutch Pathology Registry and prostate-specific antigen values from The Netherlands Cancer Registration for prostate cancer patients diagnosed between January 2017 and December 2019. We determined laboratory-specific proportions per histologic grade and unadjusted odds ratios (ORs) for International Society of Urological Pathologists Grades 1 vs. 2–5 for 40 laboratories due to treatment implications for higher grades. Pathologist-specific proportions were determined for 21 laboratories that consented to this part of analysis. The synoptic reports of 21 laboratories were used for analysis of case-mix correction for PSA, age, year of diagnosis, number of biopsies and positive cores. Results: A total of 38,321 reports of 35,258 patients were included. Grade 1 ranged between 19.7% and 44.3% per laboratory (national mean = 34.1%). Out of 40 laboratories, 22 (55%) reported a significantly deviant OR, ranging from 0.48 (95% confidence interval (CI) 0.39–0.59) to 1.54 (CI 1.22–1.93). Case-mix correction was performed for 10,294 reports, altering the status of 3/21 (14%) laboratories, but increasing the observed variation (20.8% vs. 17.7%). Within 15/21 (71%) of laboratories, significant inter-pathologist variation existed. Conclusion: Substantial variation in prostate cancer grading was observed between and within Dutch pathology laboratories. Case-mix correction did not explain the variation. Better standardization of prostate cancer grading is warranted to optimize and harmonize treatment.

The devil is in the details: an analysis of patient rights in Swiss cancer registries

Cancer registries are an important part of the public health infrastructure, since they allow to monitor the temporal trends of this illness as well as facilitate epidemiological research. In order to effectively set up such registries, it is necessary to create a system of data collection that permits to record health-related information from patients who are diagnosed with cancer. Given the sensitive nature of such data, it is debated whether their recording should be based on consent or whether alternative arrangements are possible (eg, opt-out systems where information is automatically collected but patients can later withdraw). In the recent reform of the Swiss cancer registration legislation, the lawmaker set out to implement rules about the recording of data in cancer registries that would allegedly go beyond a consent-based model, in order to balance accurate registration with respect of patient rights. However, by analysing the operational norms of the new legislation and comparing them with those of other systems, it emerges that the Swiss rules de facto closely resemble a system of registration based on informed consent—in partial contradiction with the objective pursued by the lawmaker. In this paper, we show how the details of a policy are crucial to determine its true nature and we highlight some critical elements—from an ethical standpoint—of the recently reformed Swiss policy on cancer registration.

Diffuse large B cell lymphoma (DLBCL) in patients older than 65 years: analysis of 3 year Real World data of practice patterns and outcomes in England

Background We wished to examine treatment and outcome patterns in older diffuse large B-cell lymphoma (DLBCL) patients, with a focus on the effect of route-to-diagnosis to outcome. Methods Data were extracted from Public Health England’s National Cancer Registration and Analysis Service between 2013 and 2015 included route-to-diagnosis, disease characteristics and survival for 9186 patients ≥65 years. Systemic Anti-Cancer Therapy data identified front-line regimens, cycles and doses. Results Route-to-diagnosis were emergency (34%), NHS urgent cancer pathway (rapid haemato-oncologist review <2 weeks), (29%) and standard GP referral (25%). The most common regimen was R-CHOP (n = 4392). 313 patients received R-miniCHOP (7% of R-CHOP). For all patients, 3-year overall survival (OS) for 65–79 years was 57% and for ≥80 years was 32%. Three-year OS for R-CHOP-treated patients diagnosed via emergency presentation was 54% (adjusted hazard ratio (HR) 1.63, p < 0.01) and 75% (adjusted HR 0.81, p < 0.01) on the NHS urgent cancer pathway (reference HR:1.00: GP referrals). 3-year OS was 54% for both R-miniCHOP and R-CHOP in ≥80 years. Conclusions Our comprehensive population analysis is the first to show that the NHS urgent cancer pathway is associated with a superior survival after adjusting for multiple confounders. Equivalent survival for R-CHOP and R-mini-CHOP was demonstrated in those ≥80 years.

Estimating population-based incidence of brain metastases – a comprehensive incident cohort study

Aims Brain metastases are the most common intracranial tumour and affect approximately 20% of adult cancer patients, most commonly from lung, breast, melanoma, and kidney cancer. However, the true incidence of brain metastasis is unknown. England’s cancer registration system only reliably captures brain metastases present at diagnosis (rather than those that develop later), and the same is true for US-based data. Although it is relatively easy to identify patients receiving some treatments for brain metastases (surgery, stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT)), identifying those receiving chemotherapy or no treatment is much harder. As a result, the existing literature is heavily biased towards reporting treated populations. This study attempts to find an unbiased estimate of the true number of patients developing brain metastases, based on data from a single centre. Method Cases of brain metastasis were retrospectively identified from the radiology information system database (SolitonTM). We performed a Boolean search for specific keywords in the radiology reports of all CT and MRI head scans performed at the trust between 1st January 2018 and 31st December 2019. The following keywords were searched for “metastases”, “metastatic“, “metastasis”, “mets”, “deposit”, “deposits”, “secondaries”, “secondary” and “disseminated”. Duplicate cases were then removed and the subsequent list was manually reviewed We identified all patients who received any treatment for brain metastases who were diagnosed at our centre. We only included patients with newly diagnosed brain metastases (included: leptomeningeal; excluded: skull-based metastases). We excluded patients who were diagnosed in other centres and treated here or diagnosed outside the study period. We then extracted data on primary diagnosis, admissions, and survival. Results 1192 patients had a CT or MRI of the head with a mention of “brain metastases” in the report; of these 305 were newly diagnosed with brain metastases during the study period (432 had metastases; 127 diagnosed earlier). Of these 305 patients, 217 (71.1%) were treated locally (SRS = 88; WBRT = 74; surgery = 88; systemic therapy = 16; multiple treatments = 45) and 10 (3.3%) were referred elsewhere. 78 (25.6%) patients received no treatment. Of the 217 treated patients, 124 were female, and the median age was 61. Of the 78 untreated patients, 38 were females, and the median age was 70 years old. The commonest primary diagnoses in both groups were lung (39%) and breast (21%) cancer. 16 (21%) of the untreated patients had an unbiopsied primary tumour. Median survival for patients having (any) treatment was 52 weeks compared to 5 weeks for those not having treatment. Conclusion We have presented an unbiased single-centre estimate of brain metastases occurrence. Unlike previous work, we manually reviewed all imaging reports that suggested metastasis, and included all patients diagnosed with brain metastases at any timepoint. We reduced the bias associated with being a tertiary centre by only including patients who were diagnosed here, rather than referred from other centres. 25% of our cohort received no treatment, and survival in this group is poor. This is broadly in line with the only other study on this topic (Bentley, 2019) that reported a large minority (39%) of untreated patients. Our key conclusions are: When assessing the incidence of brain metastases, studies that do not account for untreated patients are likely to significantly underestimate incidence, and over-estimate survival. Improving outcomes in patients with brain metastases might be best achieved by addressing earlier identification and intervention in those who currently receive no treatment

GlioCova: Treatment and hospital admissions for patients with GBM in England

Aims Data on the treatment and outcomes of patients with primary brain tumours in England is sparse. The GlioCova project uses linked national data from England to explore the incidence, treatment, outcomes, and treatment costs of all adult brain tumour patients in all 50,000 patients in England from 2013 – 2018. Here we present initial results from patients with glioblastoma (GBM). Method We used a linked dataset from the national cancer registration system in England including all adult patients diagnosed with a malignant or benign brain tumour between 2013 and 2018 (51,775 patients in total). Glioblastoma patients were selected based on ICD-10 codes (C70, C71, C72), morphology codes (9440, 9441, 9442), and grade (G4, G3, GX and NA) from the national cancer registry. We extracted data on treatment (radiotherapy, chemotherapy, brain surgery or biopsy) and measured how many patients who had adjuvant Temozolomide completed 6 cycles. Results We identified 15,294 glioblastoma patients. Most had glioblastoma morphology (14,924), followed by gliosarcoma (264) and giant cell glioblastoma (106). Almost all had a cranial tumour (C71) while 17 had a tumour originating in the spinal cord, cranial nerves or other part of central nervous system (C72). Median age was 66 (IQR=17) and 60% were male. 51.9% (7,935) underwent surgery; an additional 18.2% (2,784) had a biopsy; 3,701 (24.2%) out of 15,294 patients received radiotherapy (only) and 316 (2.1%) received chemotherapy (only). 5,520 (36.1%) received both radiotherapy and chemo. Out of 4,101 GBM patients receiving temozolomide after radiotherapy, only 1,535 (37.4%) completed 6 cycles. The 7,935 GBM patients who had surgery had a median length of stay in hospital of 5 days (IQR=6) while those that had a biopsy had a median of 3 days (IQR=6). Conclusion We have presented a description of treatment of all GBM patients in England over a five-year period. This is the first time we have been able to understand detailed treatment patterns at a national scale, and significantly extends previous analyses. Further work will look at patient safety indicators, variation across centres and costs of treatment. Acknowledgements We would like to thank the GlioCova Expert Advisory Group for their input and discussion. This work uses data provided by patients and collected by the NHS as part of their care and support.

P14.45 The incidence of major subtypes of primary brain tumours in adults in England 1995–2017

BACKGROUND Primary brain tumours are a complex heterogenous group of benign and malignant tumours. Reports on their occurrence in the English population by sex, age, and morphological subtype and on their incidence are currently not available. Using data from the National Cancer Registration and Analysis Service (NCRAS), the incidence of adult primary brain tumour by major subtypes in England will be described. METHODS Data on all adult English patients diagnosed with primary brain tumour between 1995 and 2017, excluding spinal, endocrinal and other CNS tumours, were extracted from NCRAS. Incidence rates were standardised to the 2013 European Standard Population. Results are presented by sex, age, and morphological subtype. RESULTS Between 1995 and 2017, a total of 133,669 cases of adult primary brain tumour were registered in England. Glioblastoma was the most frequent tumour subtype (31.8%), followed by meningioma (27.3%). The age-standardised incidence for glioblastoma increased from 3.27 per 100,000 population per year in 1995 to 7.34 in men in 2013 and from 2.00 to 4.45 in women. Meningioma incidence also increased from 1.89 to 3.41 per 100,000 in men and from 3.40 to 7.46 in women. The incidence of other astrocytic and unclassified brain tumours declined between 1995 and 2007 and remained stable thereafter. CONCLUSION Part of the increase in the incidence of major subtypes of brain tumours in England could be explained by advances in clinical practice including the adoption of new diagnostic tools, classifications and molecular testing, and improved cancer registration practices.