Cancer research in the Midland Region – the prostate and bowel cancer projects Ross Lawrenson Waikato Clinical School University of Auckland

MoH/HRC Cancer Research agenda Lung cancer Palliative care Prostate Cancer Bowel Cancer

Cancer Control New Zealand Initiatives to reduce the mortality from cancer Initiatives to reduce the impact of cancer Initiatives to reduce inequalities in access to cancer services due to ethnicity, economic status, and place of domicile How effectively new initiatives have been implemented.

Prostate Cancer RFP Research will provide a description of the types of care received by men and demonstrate the equity issues, costs and complications arising from this care. The research will also provide details of the proportion of men who are likely to undergo a biopsy after a PSA test

Our proposal Look at PSA testing in general practice Look at differences between Maori and non- Maori and urban and rural patients using national data Look at pathways of care for a cohort of men (500) diagnosed with prostate cancer Look at the costs and complications of treatment for prostate cancer in a sample of 100 men including approx 50 Maori.

Natural history Prostate cancer is a slowly growing tumour that occurs in old age. Most cancers have an indolent course during the first 10 to 15 years. Johansson (1997) showed that in a population-based cohort of men with prostate cancer after 15 years of follow up, 80% of men who had initially presented with localised disease were alive and survival was unaffected by whether or not they had received treatment. Further follow up at 15 to 20 years revealed a substantial decrease in cumulative progression-free survival.

ERSPC and PLCO Early evidence from two large randomised controlled trials of prostate cancer screening, European Randomized Study of Screening for Prostate Cancer (ERSPC) and the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO), was published in March The trials analysed men from ages 55 to 69 years, and 55 to 74 years, respectively. The European trial reported a significant absolute risk difference between the screening and control groups of 0.71 prostate cancer deaths per 1000 men. This means that 1410 men would have to be screened 1.7 times over 9 years (number needed to screen), and 48 men would need to be treated (number needed to treat) to prevent one prostate cancer death. The US study found no benefit. Both the European and U.S. trials reported significant harms associated with infection, urinary incontinence and impotence

Goteborg study From 1994 to 2008, from an eligible population of 32298, a cohort of 20,000 men aged years with no prostate cancer was randomly assigned to either a group that was invited every two years for PSA screening (n=9952) or to a control group that was not offered PSA screening (n=9952). At the beginning of the study period, the PSA threshold used for diagnosing prostate cancer was 3.0 ng/mL of blood. For consistency with the European trial, in 1999 the diagnostic cut-off was changed to 2.9 ng/mL and in 2005 it was changed again to 2.4 ng/mL to reflect recalibration of the PSA-assay. Results: In the screening group, the participation rate in at least one screening round was 76% (n=7578) and a total of PSA tests were performed. A total of 4693 positive PSA results were recorded. 33% of the participants (n= 2469) received at least one positive result and 93% of these (n=2298) had a biopsy performed. Of the enrolled men, 78% (n=15501) reached the maximum follow-up time of 14 years.

Goteborg study After 14 years of follow-up, within a core age group of 50 to 64 years, 44 and 78 prostate cancer deaths were observed in the screening group and control groups respectively. The unadjusted rate ratio for death from prostate cancer in the screening group was 0.56 (95% CI, p=0.002). This corresponds with a significant absolute risk difference between groups of four deaths per 1000 men. The incidence of prostate cancer was almost 60% greater in the screened group (see table). The all cause mortality in the two groups was 1982 in the control group and 1981 in the screened group.

Goteborg study Control GroupScreened Group Number with prostate cancer Number of prostate cancer deaths 7844 Number with prostate cancer who died of unrelated causes 54109

Treatment or intervention Options for treatment include radical prostatectomy, radiotherapy (focussed beam, or brachytherapy), or watchful waiting. We have evidence from an RCT of radical prostatectomy versus watchful waiting - fewer men in the radical prostatectomy group died of prostate cancer (30 vs. 50, P=0.01) (Bill-Axelson et al 2005). The benefit was seen mostly in men younger than 65 years. There is little convincing evidence that brachytherapy or focussed beam radiotherapy have different survival outcomes than prostatectomy. Treatment options in New Zealand vary from DHB to DHB and differences in outcomes of the various options have not been evaluated in the local setting.

Harm of treatment Treatment commonly causes moderate-to-substantial harms, such as erectile dysfunction, urinary incontinence, bowel dysfunction and on occasion death. A study by Gore (2009) found 2 years post treatment around 20% of men suffered from urinary incontinence, 60% suffered from erectile dysfunction and 10-15% suffered from problems with bowel function. Urinary incontinence was more common after prostatectomy. Bowel dysfunction was more common after radiation therapy. All three modalities profoundly affect sexual function. These harms are important because some men with prostate cancer who are treated may never have developed symptoms related to cancer during their lifetime.

Consideration of cost Screening large numbers of people is expensive and can divert both human and financial resources from other health services. The costs of screening for prostate cancer include: –GP time in counselling men about the benefits and risks –the cost of the test –the cost of diagnosis with prostatic biopsy, –the pathology costs needed to make the diagnosis, –the cost of counselling for those men who treatment is being suggested, –the costs of surgery or radiotherapy (or watchful waiting). These costs need to be balanced against the cost of investigating and treating symptomatic patients. Ideally, a cost-effectiveness analysis should be undertaken before any screening program is considered.

Prostate Cancer

Ethnicity

PSA testing in NZ 33 percent of men over 50 years of age had a PSA test in percent over 50 years had a test at some stage over the three-year period from 2005 to % of men aged had a test over a one- year period and approximately 60% of men in this age group have had a test over a three year period.

PSA testing in GP We know that testing is being carried out Don’t know who is driver of this testing – GP or patient? Don’t know what GPs do when find a raised PSA Don’t know whether differences in access to screening eg for Maori or rural patients

Study 1 – PSA test Recruit 20 practices across the Midland Network Half rural, half with good proportion of Maori Identify all men aged over 40 years Find proportion with a PSA test in 2010 Look at results and audit referral patterns and biopsy rates Compare, rural/urban and Maori to non-Maori

Study 2 - Review national data Good data on Māori already published Not so good info on urban rural differences or by region for last 15 years Will follow similar study to our study on breast cancer Will also look at cause of death

Study 3 pathways of care Approx 350 men diagnosed in Midland region with prostate cancer each year Want to establish path from presentation to GP, referral to specialist, diagnosis, treatment options and follow up Particular interest is subset who have been diagnosed through screening Will try and look at variations by age, social class ethnicity and domicile

Study 4 – costs and complications Potential benefit of screening have been highlighted by ERSPC and Goteborg study Complications of treatment are well recognised. –Urinary incontinence –Bowel dysfunction –Erectile dysfunction –Infection Other less well recorded –Depression –Social/family impact

Costs Costs incurred following diagnosis Costs incurred by doing a PSA test

Time frame Three project –Currently undergoing study 1 –Study 2 will begin later this year –Study 3 will begin in 2012 –Study 4 will also begin later in 2012

Bowel Cancer – the Auckland Study PI Prof M. Findlay

Bowel Cancer Bowel cancer is the most common cancer in New Zealand and we have one of the highest death rates from bowel cancer in the developed world. There are approximately 1200 deaths each year and about 2700 new cases of bowel cancer each year. In May 2008 the Minister of Health announced that a New Zealand bowel cancer screening programme would be established.

Maori There are clear inequalities in bowel cancer between Māori and non-Māori. Evidence shows that Māori are less likely to be diagnosed, and more likely to die from bowel cancer.

Colorectal

Aims and/or hypothesis Look at urban/rural disparities as well as socioeconomic and ethnicity factors in the management of colorectal cancer patients following diagnosis across New Zealand Hypothesis that rural patients have inferior access to timely and appropriate treatment options and therefore worse outcomes. The aim of the project is to use Key Performance Indicators (KPIs) of service delivery to identify differences in the management of urban and rural patients, and through formation of a national advisory group develop recommendations for service change that can later be used to assess improvement.

Proposed methodology A national cohort of all patients that had a colorectal cancer diagnosis during years 1 January December 2008 as identified by the New Zealand Cancer Registry (we expect approximately 5600 cases). Data will be extracted from hospital systems and patient medical records. (With help of Cancer Networks) Data will be used to calculate the proportion of patients meeting each KPI. Differences in KPIs by rurality, socioeconomic status (NZDep1) and ethnicity will be examined. Factors predictive of short-term (3-year) survival and disease- free survival will be examined.

Indicators to be collected from medical records ComparisonsSite: ColonSite: Rectal Rural/urban Etnicity Social deprivation Presentation:  acute vs. non-acute Presentation:  acute vs. non-acute Stage at diagnosis (TNM): Staging process Staging process Treatment  Surgical procedure  adjuvant chemotherapy  undergoing resection of secondaries  review at an MDM  participation in a clinical trial Treatment  Surgical procedure  adjuvant chemotherapy  undergoing resection of secondaries  review at an MDM  participation in a clinical trial. Management  median time referral receipt to diagnosis  median time diagnosis to treatment  median time to initiation of adjuvant treatment Management  median time referral receipt to diagnosis  median time diagnosis to treatment  median time to initiation of adjuvant treatment Outcomes  progression free survival at 3 years  % alive and stoma-free at 3 years Outcomes  progression free survival at 3 years  % alive and stoma-free at 3 years

Additional work To ensure explanatory power for Māori and Pacific an additional cohort using a further 4 years of data will be collected.

Summary Data on management of cancer is essential to improving treatment and outcomes for people with cancer. Midland Regional Cancer Network is essential to helping explore inequalities particularly with regards rural patients and for Maori