SUSPECTED CANCER IN PRIMARY CARE
Guidelines for investigation, referral and reducing ethnic disparities
By the NZ Guidelines Group, September, 2009
This guideline aims to help practitioners in primary care:
1. recognise the signs and symptoms that are suggestive of a cancer diagnosis in primary care
2. refer people in a timely manner where cancer is suspected
3. be aware of the investigations that may be appropriate to undertake in the primary care setting.
As this guideline is focused on referral of people presenting to primary care with signs or symptoms suggestive of cancer, screening in asymptomatic people is beyond the guideline scope.
Therefore, no recommendations have been made on management in relation to findings from routine prostate serum antigen (PSA) screening.
For further information on PSA screening, readers are referred to Testing for Prostate Cancer:Information for Men and their Families114 and Testing for Prostate Cancer: A Consultation Resource,115 published by the New Zealand Guidelines Group in 2008.
These documents are available on the New Zealand Guidelines Group website.
Grade C means the recommendation is supported by international expert opinion.
Epidemiological background – New Zealand population
Prostate cancer is the third most common cause of male cancer deaths in New Zealand (after lung and colorectal cancer).
In 2004, 85% (n=496) of prostate cancer deaths occurred in men aged over 70 years.
Data on prostate cancer survival give a cumulative relative survival of approximately 86% after five years. In the first year, the chance of survival is 94% and after four years of survival, there is a 98% chance of surviving to the end of the fifth year.
European/Other New Zealanders
Prostate cancer mortality rates increased among European/Other men through the 1980s and early to mid 1990s, but have stabilised since then. Overall, from 1981–1984 to 2001–2004 rates have increased by 10%.
The incidence of prostate cancer in Mäori men was lower than in non-Mäori during 1996–2001. However, the mortality:incidence ratio was 29% for Mäori and 15% for non-Mäori.
In the first year, the chance of survival is 87% for Mäori men and 94% for non-Mäori.80 Mäori men when compared to non-Mäori, were less likely to be diagnosed with this disease but, after diagnosis, were more than twice as likely to die as a result of it. Mäori men were more likely to be diagnosed at a later disease stage.
During 1996–2000, Pacific men aged 65 years or older had higher prostate cancer registration rates and higher mortality rates compared to the total New Zealand population.
Background to recommendation development
Risk factor consideration is an integral part of practitioner assessment of a symptomatic patient. The non-systematic review below summarises the key risk factors for prostate cancer.
Summary of findings
The NICE Referral Guidelines for Suspected Cancer literature review (National Collaborating Centre for Primary Care. Referral guidelines for suspected cancer in adults and children. Part 2. London: National Collaborating Centre for Primary Care; 2005) identified that although prostate cancer was rare in men aged under 45 years, beyond this age the incidence rose sharply.
Their literature review also cited a systematic review by Zeegers et al. in 2003, which reported (from a meta-analysis using a random effects meta-regression model) that the relative risk of prostate cancer among first-degree family members (father, brother) was 2.53 (95% CI 2.24–2.85).
Additional risk information relating to age and family history is provided in the NZGG resource Testing for Prostate Cancer: A Consultation Resource.
Signs and symptoms
A systematic review of the literature sought comparative studies of symptom recognition/identification for prostate cancer in primary care settings or in primary care populations. Screening studies and studies conducted in secondary care settings were excluded. Due to a lack of relevant literature, all studies, irrespective of their methodological design, were presented to the GDT (Guidelines development Team) to consider in the development of recommendations.
Summary of findings
One UK primary study of case-control design,116 published since the NICE guideline, was identified by the literature review. The NICE recommendations for referral for suspected prostate cancer were based on cohort studies, non-experimental descriptive studies, case-control or case-series studies and expert opinion.
The literature review identified that although prostate cancer often presented with symptoms that indicated urinary outflow obstruction, other symptoms included urinary tract infection and signs of metastatic spread (eg, bone pain). It was noted that although the majority of prostate cancers can be palpated on digital rectal examination, an abnormal examination result may result from other benign conditions.
In a methodologically robust case-control study116 of patients aged 40 years or more with prostate cancer (n=217), signs and/or symptoms independently associated with the cancer in the two years before diagnosis included urinary retention, impotence, frequency, hesitancy, nocturia, haematuria, weight loss, abnormal rectal examination deemed benign and abnormal rectal examination deemed malignant.
The highest positive predictive values (PPV) of these individual signs and/or symptoms were for abnormal rectal examination deemed malignant (12.0%, 95% CI 5.0–37.0%) and urinary retention (3.1%, 95% CI 1.5–6.0%).
The highest PPVs for two signs and/or symptoms were for abnormal rectal examination deemed malignant combined with either hesitancy or frequency/urgency or nocturia (range, 10.0–15.0%), for nocturia combined with weight loss (12.0%) and for abnormal rectal examination deemed benign combined with weight loss (9.4%).
A systematic review of the literature sought diagnostic studies in which primary care patients with suspected prostate cancer underwent one or more of the investigations listed below:
• urine microscopy
• CT scan
• urine cytology.
The list of investigations for inclusion in the literature review was produced by the GDT members by informal consensus.
Screening studies and studies conducted in secondary care settings without a source population of primary care patients, or where primary care patients were not analysed separately from tertiary referrals, were excluded.
Due to a lack of relevant literature, all studies, irrespective of their methodological design, were presented to the GDT to consider in the development of recommendations.
Summary of findings
No secondary or primary studies, published since the NICE guideline, were identified by the literature review.
The NICE guideline recommendations were based on cohort studies, non-experimental descriptive studies, case-control or case-series studies and expert opinion.
The NICE literature review identified evidence that the PSA test has moderate sensitivity and specificity for prostate cancer.56 An NZGG resource on PSA testing reports the estimated sensitivity (‘true positives’) as 74–84%, and the estimated specificity (‘true negatives’) as 90–94%.
Based on the NICE guideline literature review and the evidence identified by NZGG, the GDT agreed with the NICE recommendations that a man with a hard, irregular prostate required urgent referral and that a man with unexplained lower back pain, bone pain or weight loss should be recommended to have a digital rectal examination and a PSA test.
In contrast to NICE, the GDT did not consider it necessary for a man with erectile dysfunction to undergo these tests. This symptom was therefore excluded from the guideline recommendations.
The GDT also agreed with some of the NICE recommendations surrounding PSA testing. These included recommendations related to the need to urgently refer men with lower urinary tract symptoms and 1) a normal prostate on examination and a raised, or rising, age-specific PSA result 2) a high PSA level.
However, the GDT chose to define a high PSA as 10 ng/ml or more, and quoted an example of an age-based PSA level from a recently published NZGG resource on PSA testing.
The GDT also agreed with NICE on the importance of excluding urinary infection prior to PSA testing and the need to postpone the test for a minimum of a month following treatment of a proven infection.
The GDT chose to exclude a NICE recommendation on the course of action necessary when an asymptomatic man had a borderline PSA, as this was beyond the scope of the guideline.
Although NICE noted that a man with lower urinary tract symptoms should be recommended to have a digital rectal examination and a PSA test, the GDT considered this inappropriate.
They chose instead to include a good practice point to highlight their view of the importance of conducting these tests in older men.
During discussions, the GDT acknowledged that a man with lower urinary tract symptoms with features of renal failure secondary to significant outflow obstruction required investigation. However, because this guideline relates to cancer referral, no specific recommendation was considered appropriate for inclusion.
The GDT also chose to address two additional areas. Good practice points were therefore incorporated on how to manage patients found to have both a large, smooth prostate on digital rectal examination and macroscopic haematuria.