Intended for healthcare professionals

Practice Uncertainties

Do men with lower urinary tract symptoms have an increased risk of advanced prostate cancer?

BMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k1202 (Published 03 May 2018) Cite this as: BMJ 2018;361:k1202
  1. Jenny Østerø í Jákupsstovu, research assistant1,
  2. John Brodersen, professor1 2
  1. 1Centre of Research and Education in General Practice, Department of Public Health, University of Copenhagen, Denmark
  2. 2Primary Health Care Research Unit, Region Zealand, Denmark
  1. Correspondence to tmw139{at}alumni.ku.dk

What you need to know

  • It is uncertain if lower urinary tract symptoms are associated with an increased risk of advanced prostate cancer

  • Do not routinely offer prostate specific antigen (PSA) testing in men with only lower urinary tract symptoms and no risk factors for prostate cancer

  • Explain the limitations and harms of a PSA test to the patient in terms of downstream procedures, and the possibility of being diagnosed with prostate cancer that might not cause him symptoms or shorten his life

A 72 year old man complains of increased frequency of urination, particularly at night. He also describes a sense of incomplete voiding and a poor stream. He is concerned about whether he might have prostate cancer, and wants to be reassured that this is not the case.

More than half of all men over 50 report problems with urinating.1

Grouped as lower urinary tract symptoms (LUTS), these signify problems with the storage and/or voiding of urine, and are often caused by benign prostatic enlargement.1 LUTS are habitually considered a possible symptom of prostate cancer,2 and qualitative studies show that men with LUTS are worried about having prostate cancer and consult a doctor to seek reassurance.345 Prostate cancer is one of the most diagnosed cancers in men worldwide. During the previous two to three decades, prostate cancer incidence has greatly increased in high income countries; however, at the same time the mortality of prostate cancer has stayed stable or decreased slightly. Advanced prostate cancer is potentially fatal. In contrast, indolent prostate cancer is per definition harmless and does not cause morbidity or mortality. Moreover, indolent prostate cancer is the most frequent form of prostate cancer, eg, autopsy studies estimate the mean prevalence of indolent prostate cancer to be 59% in men >79 years.6 Collated with the high prevalence of LUTS in older men, a connection between LUTS and indolent prostate cancer is nearly unavoidable. Most general practice clinical guidelines (table 1) recommend doctors to consider the prostate specific antigen (PSA) test in men with LUTS for prostate cancer detection.791011 However, it is uncertain if men with LUTS have increased risk of advanced or potentially fatal prostate cancer and therefore, if they should be offered the PSA test.

Table 1

Guidelines for PSA testing in men with LUTS

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The controversy of PSA screening is much discussed, and now a consensus on not screening asymptomatic men is emerging (appendix 1).1213 Data from the five Nordic countries suggest that, despite a rise in the diagnosis of prostate cancer, particularly since the introduction of PSA testing, there has been little change in death from the disease (fig 1).14 Patterns such as these suggest overdiagnosis. Recognising the lack of benefits in early prostate cancer detection,1215 PSA testing in men with LUTS places them at risk of being diagnosed with indolent prostate cancer and being treated for a condition that would not result in either morbidity or mortality.

Fig 1
Fig 1

Prostate cancer incidence and mortality in Nordic countries 1953-201314

What is the evidence of uncertainty?

Search strategy and study selection

We searched PubMed in September 2016 with the free-text and MESH-terms: “lower urinary tract symptoms” OR “LUTS” AND “prostatic neoplasm” OR “prostate cancer” OR “prostatic cancer” OR “cancer of the prostate.” We identified four16171819 observational studies that examine whether LUTS is predictive of advanced and potentially fatal prostate cancer. We included studies conducted in a general practice population or screening population, with transparent identification of people with and without LUTS and a specified PSA level as indication for biopsy. We excluded studies conducted in a selected population, eg, referred patients, studies where the differentiation of people with and without LUTS was not clear, and studies that had other indications for biopsy, eg, abnormal digital rectal examination.

The current evidence is limited to observational studies primarily conducted in PSA screening populations and suggests that men with self-reported LUTS are not at increased risk of having advanced or potentially fatal prostate cancer compared with men without LUTS (see table 2 and appendix 1).

Table 2

PICO summary of evidence

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These studies are large and population based but they vary in design. Three161718 of four studies were conducted in PSA screening populations. The Norwegian19 and Swedish17 studies used longitudinal follow-up, and the other two studies1618 used a cross-sectional design, although they were based on PSA screened cohorts. The tools used to record symptoms are different and there is a potential for bias. Three161819 of the four studies used a validated self-reported questionnaire to measure LUTS. In two studies,1819 asymptomatic men were asked to complete a questionnaire on lower urinary tract symptoms, and in the other two studies1617 men with raised PSA levels were asked about symptoms. The outcomes varied in terms of severity of prostate cancer and the time period. Only one study19 recorded prostate cancer incidence and mortality nine years later.

Three161718 of four studies offered biopsy when PSA was ≥3 ng/ml.9 Hence, the true association between LUTS and prostate cancer now or in the future remains unknown, and the discovered association can only be applied for men with a raised PSA level. An American population based cohort study has shown that increased diagnostic intensity among men who present with LUTS is possible for the association between LUTS and prostate cancer observed in some studies.20

Is ongoing research likely to provide relevant evidence?

We searched clinical trial registers (clinicaltrials.gov, controlled-trials.com, who.int/trialsearch) in September 2017 for observational studies of associations between LUTS and current or future prostate cancer diagnosis. We did not identify any relevant studies examining whether LUTS are predictive of advanced or potentially fatal prostate cancer or studies offering PSA testing in men with LUTS for cancer detection.

What should we do in light of the uncertainty?

There is no consensus regarding PSA testing in men with LUTS, and most guidelines recommend shared decision making (table 1).791011 In addition to cancer detection, urologists request the PSA test in men with LUTS to assess the prostate volume and predict prostate growth and clinical progression.21 Some guidelines support the use of clinical nomograms in selected patients to determine the risk of high grade prostate cancer.10 Otherwise, current guidelines recommend a PSA test if the patient’s LUTS are suggestive of bladder outlet obstruction,7 if the man is over 40 with unexplained symptoms such as lower back pain, bone pain, or weight loss suggestive of metastatic prostate cancer,10 or there is a family history of prostate cancer.11 We have not identified evidence that these recommendations improve the prognosis in men with LUTS.

There is insufficient evidence to recommend PSA testing in men with only LUTS and no other known risk factors for prostate cancer.

Explore why your patient is concerned about prostate cancer, and assist him in making an informed choice regarding PSA testing. Ask for age, family history of prostate cancer, and ethnicity to assess risk for prostate cancer.

Offer to perform a physical examination including a digital rectal examination that can help detect prostate enlargement or cancer. Offer a urine dipstick test to detect blood, glucose, protein, leucocytes, and nitrites. You might ask the patient to complete a urinary frequency volume chart to assess the severity and perhaps help pinpoint the type of the problem and furthermore aiding the decision making regarding medical treatment.7

Discuss with your patient the lack of direct evidence that LUTS symptoms in isolation suggest prostate cancer. Explain the possible limitations and harms of a PSA test such as downstream procedures, and the possibility of being overdiagnosed with prostate cancer and related treatment. When communicating the uncertainty about testing, using terms like “abnormal indolent cells in the prostate gland” rather than “localised prostate cancer” might reassure the patient and reduce patient preferences for aggressive management responses to a low risk condition.22

Recommendations for further research

  • A prognostic intervention study to evaluate if men with LUTS are overdiagnosed with prostate cancer if they have a PSA test, and how the PSA test affects their prognosis. Men with LUTS in general practice would be randomly selected to receive PSA testing or not. Both groups would be offered usual care including a digital rectal examination, urinary frequency volume chart, urine flow rate examination, and pharmacological or surgical treatment for their LUTS in discussion with their healthcare provider. Primary outcomes include prostate cancer: localised or disseminated, prostate cancer mortality and all-cause mortality. Secondary outcomes include quality of life, morbidity, and treatment.

  • A large prognostic observational cohort study including men in general practice with baseline assessment of LUTS and other factors potentially predictive of prostate cancer. The cohort should be prospectively followed and prostate cancer related outcomes measured. This study might reveal predictors of advanced prostate cancer and potentially help develop a clinical nomogram to aid decision making in men with LUTS.

  • Research for new biomarkers capable of distinguishing between low grade and high grade prostate cancer

What patients need to know

  • There is no evidence that problems with urinating suggest advanced prostate cancer

  • Your doctor will perform a digital rectal examination and might discuss prostate specific antigen (PSA) testing if you have a family history of prostate cancer in addition to lower urinary tract symptoms (LUTS)

  • Be aware of the risk of overdiagnosis and overtreatment of an indolent prostate cancer if you have a PSA test with LUTS as a single symptom with no other risk factors

Education into practice

  • How do you discuss lower urinary tract symptoms with a patient who is concerned about the risk for prostate cancer?

  • To whom do you consider offering a PSA test for prostate cancer? Does this article offer you ideas for change?

  • How do you explain the benefits and harms of testing for prostate cancer? Are there ways you could alter this?

  • If you were to make a leaflet at your practice for men with LUTS, what information about prostate cancer testing would you include?

How patients were involved in the creation of this article

A man who had a PSA test as part of medical examination kindly agreed to review this article. He shared his concern regarding the high rate of indolent prostate cancer in older men, but was also concerned about overdiagnosis and said a diagnostic label could cause fear in patients. He suggested that doctors consider the personal context of the patient in the diagnostic process and stressed the need for patient information tools, especially information on potential harms. We have summarised the current evidence and ways in which doctors might provide this crucial information to patients.

Footnotes

  • This is one of a series of occasional articles that highlight areas of practice where management lacks convincing supporting evidence. The series advisers are Sera Tort, clinical editor, and David Tovey, editor in chief, the Cochrane Library. To suggest a topic for this series, please email us at uncertainties{at}bmj.com

  • We would like to extend our sincerest thanks and appreciation to Iona Heath for her critical comments and linguistic editing.

  • We have read and understood The BMJ policy on declaration of interests and declare that we have no competing interests.

  • Provenance and peer review: Commissioned, based on an idea from the author; externally peer reviewed.

References

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