1. UK Hospitalizations due to Stroke in Prostate Cancer Patients
Treated with Androgen Deprivation Therapy (ADT)
Jefferies ER1, Bahl A2 , Hounsome L3, Eylert MF4, Verne J3, Persad RA5
MP34: Prostate Cancer III:
Poster 937
1Department of Urology, Cheltenham General Hospital, UK. 2Bristol Haematology and Oncology Centre, Bristol, UK, 3South West Public Health Observatory, Bristol, UK. 5Department of Urology, Bristol Royal Infirmary, Bristol, UK, on behalf of the PHONIC Collaboration
Abstract
ADT is well known to improve quality of life in patients with advanced prostate cancer, however deleterious side-effects on cardiovascular health have been reported. Only small volume studies have been produced in Europe on this subject to date.
Materials and Methods
Our database was prepared from Hospital Episode Statistics (HES) of the Department of Health in England. We extracted episodes for ICD-10, I61-64 and G459 I to identify admissions for intracerebral haemorrhage, infarction, stroke (not specified as haemorrhage or infarction) and transient ischaemic attacks (TIA’s) respectively. We selected all men, all prostate cancer patients (1990-onwards) and all prostate cancer patients on confirmed ADT. The rates of event were calculated as rate of events per 1,000 person years. Denominator for rate is defined by prevalence calculations: period prevalence for is calculated, based on all prostate cancer registrations, by five-year age-band.
Results
There were admissions to hospital for stroke/TIA of patients diagnosed with prostate cancer were known to be treated with ADT. There is a strong statistically significant relationship between ADT and stroke/TIA admissions to hospital across all age ranges (see Fig).
Conclusions
Keating NL (J Natl Cancer Inst 2010;102:39-46) published the first stroke data in prostate cancer patients treated with ADT, finding an overall 22% increase in stroke incidence. Our data agrees with these findings, indeed suggesting an even stronger link – a statistically significant age-related risk of between 39% and 173%.
ADT is a valuable tool in the management of advanced prostate cancer but clearly the side effects of ADT need to be recognised and managed. Further good quality prospective trials are required to evaluate the link suggested by retrospective studies.
Introduction
Androgen Deprivation Therapy (ADT) is well known to improve the quality of life in patients with advanced prostate cancer. It has also been found to have a survival advantage when used as an adjunct to radiotherapy. However in the last decade deleterious side effects have been reported: including changes in body composition, bone mineral density and lipid profile, the development of insulin sensitivity, diabetes and cardiovascular disease.
Keating et al (J Natl Cancer Inst 2010;102:29-46) published the first suggestion that ADT for the treatment of prostate cancer, could increase the development of cerebrovascular disease. – finding a statistically significant increase of 22% in the ADT group.
Only small volume studies have been published on this subject in Europe and there are currently no preventative guidelines advised at present.
Methods
The Hospital Episodes Statistics (HES) database is a data warehouse containing all the information on UK National Health Service [NHS] and NHS-funded hospital admissions in England. We extracted episodes from this for years 2004 – We selected men with an ICD-10 C61 diagnosis (malignant neoplasm of prostate) from the National Cancer Data Repository [NCDR] (contains all registrations for new cancers in England as supplied by the regional cancer registries) with a diagnosis date after 01/01/1990. We then extracted episodes containing ICD-10 I61-64 and G459 to give us admissions to hospital for intracerebral haemorrhage/infarction, stroke (not specified as haemorrhage or infarction) and transient ischaemic attacks (TIA’s) respectively.
The process was then repeated for the subset of patients which had been “flagged” on NCDR as having received ADT. The drawback of the “flagging” system is it only indicates whether ADT has been administered – the information as to which type, duration or as to whether it was used in the primary or adjuvant setting is not available.
Patients were grouped into five-year age bands on age at admission. The event rates were calculated as rates per 1000 person years. The denominator for these events were calculated as the period prevalent population of prostate cancer patients, both in total and for ADT patients, with all diagnoses (excluding death-certificate only) since 1990 counted. The background rates were selected by counting all HES episodes and then expressing as age-specific rates of episodes per 1000 person years, based on Office of National Statistics mid year population estimates.
Due to the limitations of the HES data and also the limitations of the data collected by the regional cancer registries, information such as the PSA level, tumour stage and the presence of metastasis was not available and is accepted as a significant limitation of this study.
Results
Between 2004 and 2007, there were 870,105 men diagnosed with prostate cancer above 55 years of age. 147,637 men were flagged as receiving ADT as part of their treatment, compared with 722,468 flagged as not receiving ADT, or this information was unknown.
In total, over the 3 year period, there were 16,225 admissions with a diagnosis of stroke/TIA with a concomitant diagnosis of prostate cancer. 3,685 admissions occurred in the ADT group compared to 12,540 admissions in those not on ADT. Thus there is a 44% increase in cerebrovascular admissions between the two groups per unit head.
When compared by 5 year age band, there is a strong significant difference between the two groups across all age ranges (see below) with the rate of increase ranging from a 39% (in the age group) to 173% (in the age group).
Conclusions
Retrospective US data has shown a strong link between ADT use and stroke – our UK data has shown an even stronger, age related link of up to 173%. This study adds to the increasing number of retrospective publications which question ADT’s cardiovascular safety profile, and again calls for further good quality trial evidence regarding the screening and management of ADT. ADT clearly is a valuable tool in the management of advanced prostate cancer, but in our ever aging population where prostate cancer and cardiovascular disease are at their peak – can we afford to use a treatment with such a significant potential side effect profile without taking it seriously?