Background
Prostate cancer is an epidemic of the modern era and, despite efforts to improve awareness, it remains true that mortality has barely changed over the decades, driven largely by late presentation .
There is a strong public perception that male urinary symptoms are one of the key indicators of prostate cancer, and this continues to be part of the messaging in national guidelines and media health campaigns. This narrative, however, is not evidence-based and may be seriously hindering efforts to encourage early presentation.
Discussion
Anatomically, prostate cancer arises most frequently in the peripheral zone , while urinary symptoms result from compression of the urethra by the enlarged prostate more centrally . Biopsy studies show that the average prostate volume is actually smaller in men who have (early) prostate cancer compared to those with benign biopsies. This inverse relationship between prostate size and the likelihood of cancer is so strong that PSA density (PSA corrected for prostate volume) is known to be significantly more accurate in predicting a positive biopsy than PSA alone.
Therefore, this disconnection between scientific evidence and current perception is very striking. There is also evidence that using symptoms to investigate possible cancer may lead to a higher proportion of men presenting with locally advanced or metastatic disease compared to PSA testing or screening programs.
Concerns about healthcare services being overwhelmed if men are encouraged to get tested without symptoms may also be overblown, with more recent approaches to reducing over-investigation and treatment. In this article, we explore the link between urinary symptoms and prostate cancer and propose that public and professional messages need to change .
| PSA density is calculated as total PSA (ng/ml) divided by prostate volume (ml). An optimal PSA density threshold of 0.08 was identified with a negative predictive value of 96% for clinically significant disease. These data suggest that men with a PSA density of 0.08 or less harbor a very low risk of clinically significant prostate cancer. |
Prostate cancer and gland size
Bladder outlet obstruction (most often due to a benign enlargement of the prostate) and its symptomatic manifestations, difficulty with flow, hesitancy, nocturia and poor flow, are the most common symptoms leading to a man to his GP and taken for a PSA test. The relationship between prostate size and cancer has been widely explored since the early days of PSA and routine biopsies.
Karakiewiz et al. were among the first to report that mean prostate volume was smaller in men with prostate cancer compared to those with benign biopsies. Other studies have since reported identical findings. In a meta-analysis compiled by Moolupuri et al., 28 of 30 studies showed a clear inverse relationship between prostate size and the chance of finding prostate cancer on biopsy. The remaining 2 studies were equivocal and neither showed a positive correlation.
This relationship is so strong that PSA density (PSA corrected for prostate volume) is now known to be significantly more accurate than PSA in predicting a positive biopsy and is used in daily clinical practice. In an elegant computer simulation, Lorenzo et al. They postulated that an enlarged prostate could, in fact, cause mechanical suppression of tumor growth , which may explain the inverse relationship between size and cancer detection.
One caveat is that many of these studies were performed before pre-biopsy MRI to guide biopsies (as in modern pathways) and tumors may have been harder to find in larger prostates. However, a recent study from our own unit has identified that the size-cancer relationship remained the same (inverse) in men investigated using MRI-guided biopsies.
Lower urinary tract symptoms (LUTS) and prostate cancer
Of course, overall size alone does not explain all lower urinary tract symptoms. Anatomically, early-stage cancer should not be expected to cause urinary symptoms. The most common site of malignancy (70%) is the peripheral zone , while urinary symptoms as a result of prostatic enlargement (benign) occur due to growth of the transitional and central zones . The origins of a causal link between LUTS and cancer are difficult to discover, but are likely related to the pre-PSA era before formal studies on this topic.
One of the only large epidemiological studies to report an association was the HUNT 2 study (conducted between 1995 and 2007 in Norway). But even this study found a paradoxical link with localized, but not advanced or fatal, prostate cancer. The authors concluded that urinary symptoms were not caused by prostate cancer and that screening for early cancers on the basis of urinary symptoms was not warranted.
There are more recent level 1 data from randomized controlled screening trials on LUTS and prostate cancer. Almost 10 years ago, the Gothenburg screening trial investigated the incidence of urinary symptoms and cancer detection in men with an elevated PSA (using a threshold of ≥3 ng/ml).
Not only did they not find an association, but they observed an inverse relationship between symptoms and the possibility of a positive biopsy.
More recently, the UK PROTECT trial also looked in detail at men’s self-reported LUTS scores: for each urinary score domain there was no association or a negative association with more severe symptoms and prostate cancer. The authors concluded that a lack of urinary symptoms may, in fact, be an indicator of a higher likelihood of cancer. These and many other similar studies provide fairly compelling evidence that LUTS and prostate cancer are not positively linked , in fact, they may be inversely associated , and when present, they are more likely to be (at most) coincident.
Conclusion
To improve early diagnosis rates, we call for a clear and strong message that prostate cancer is a silent disease , especially in the curable stages, and men should come forward for testing, regardless of whether they have symptoms or not .
This should be done in parallel with other ongoing efforts to raise awareness, including focusing on men at higher risk due to their racial ancestry or family history. While the current resurgence of interest and debate about prostate cancer screening is timely, changing this message by counseling bodies, charities and the media may be a simple first step in improving screening. earlier presentation and therefore cure rates.
Key messages
- Waiting for bothersome lower urinary tract symptoms as a trigger to see a GP about prostate cancer can delay earlier diagnosis and treatment.
- There is no evidence of a causal link between prostate cancer and prostate size or bothersome male urinary symptoms. In fact, most evidence points to an inverse correlation .
- Modern image-based diagnostics and risk-adapted management strategies have reduced the risks of overinvestigation and overtreatment that previously deterred further promotion of PSA testing in men without symptoms.
- Now is the time to change the message of early, curable prostate cancer as a primarily asymptomatic disease to encourage more men to come forward and get tested sooner.
Comments
Men with early, curable stages of prostate cancer are missing opportunities to have their cancer detected because national guidelines and media health campaigns focus on urinary symptoms despite a lack of scientific evidence, experts say from the University of Cambridge.
Prostate cancer is the most common type of cancer in men. According to Cancer Research UK , more than 52,000 men are diagnosed with prostate cancer each year and there are more than 12,000 deaths.
More than three quarters (78%) of men diagnosed with the disease survive for more than ten years , but this proportion has barely changed over the last decade in the UK, largely because the disease is detected at an early stage. relatively late . In England, for example, almost half of all prostate cancers are detected at stage three of four (with stage four being the last stage).
Although there is no evidence of a link between urinary symptoms and prostate cancer, national guidelines, health advice and public health campaigns continue to promote this link. In a review published in BMC Medicine , Cambridge researchers argue that this is not only not helpful , but may even deter men from seeking early testing and screening for potentially treatable cancer.
"When most people think about the symptoms of prostate cancer, they think about problems urinating or the need to urinate more frequently, especially at night," said Vincent Gnanapragasam, professor of urology at the University of Cambridge and honorary consultant urologist at Addenbrooke’s. Hospital, Cambridge. “This misperception has lasted for decades, despite very little evidence, and potentially prevents us from detecting cases at an early stage.”
An enlarged prostate can cause the urinary problems that are often included in public health messages, but evidence suggests that this is rarely due to malignant prostate tumors . Rather, research suggests that the prostate is smaller in cases of prostate cancer. One recent study, the UK PROTECT trial, even went so far as to say that a lack of urinary symptoms may, in fact, be an indicator of a higher chance of cancer.
Screening programs are one way that cancers are often detected at an early stage, but in the case of prostate cancer, some argue that such programs risk overburdening health services and leading men to receive treatment for a relatively benign disease.
Testing for prostate cancer involves a blood test that looks for a protein known as prostate-specific antigen (PSA) that is produced only by the prostate gland; however, it is not always accurate. PSA density is significantly more accurate than PSA alone in predicting a positive biopsy and is used in daily clinical practice.
Researchers point to evidence that there is a misconception that prostate cancer is always symptomatic: A previous study found that 86% of the public associated prostate cancer with symptoms, but only 1% knew it could be asymptomatic.
“We urgently need to recognize that the information currently provided to the public risks giving men a false sense of security if they do not have any urinary symptoms,” Professor Gnanapragasam said.
“We need to emphasize that prostate cancer can be a silent or asymptomatic disease, particularly in its curable stages. Waiting for urinary symptoms can mean missing opportunities to get the disease when it is treatable.
“Men should not be afraid to talk to their primary care doctor about getting tested and the value of a PSA test, especially if they have a history of prostate cancer in their family or have other risk factors, such as race.” black or mixed. ethnicity.”
The researchers say they are not advocating an immediate screening program and acknowledge that changes in messaging could mean more men approach their GPs for a PSA test, which could result in unnecessary investigations and treatments. However, they argue that there are ways to reduce the risk of this happening. These include using algorithms to assess an individual’s risk and whether they need to be referred to a specialist, and for those who are referred, MRIs could help rule out ’ indolent’ (mild) disease or negative results, reducing risks. risks of an unnecessary biopsy.
“We are calling on organizations such as the NHS, as well as patient charities and the media, to review current public messaging,” Professor Gnanapragasam said.
“If men knew that just because they have no symptoms does not necessarily mean they are cancer-free, then more might accept offers of testing. “This could mean more tumors are identified at an earlier stage and reduce the number of men who experience late presentation with an incurable disease.”
Final message We are calling on governing bodies, charities and the media to take urgent action to review current public messaging and referral recommendations. Paramount is to abolish public messages that suggest that prostate cancer directly causes urinary symptoms. Maintaining this fallacy is misleading. Instead, efforts should be made to raise awareness that prostate cancer does not manifest with urinary symptoms. To be clear, we are not advocating for an immediate screening program nor are we calling for changing existing pathways (e.g., incidental screening of men who see primary care physicians for urinary symptoms). We recognize that the latter remains an important route for men to be detected and, in particular, for men who may not access health information resources or in hard-to-reach sociodemographic groups. For many of these men, the only reason to see a doctor is if they have bothersome symptoms. However, if men knew that just because they have no symptoms does not mean they do not have cancer , more men might accept offers of testing. This could mean more tumors are identified at an earlier stage and reduce the number of men who experience late presentation with an incurable disease. Eventually, we hope an intelligent tiered screening program will be possible, but until then, a simple change in messaging to correct years of misinformation would be a good starting point. |
Reference: Gnanapragasam, VJ, et al. Urinary symptoms and prostate cancer—the misconception that may be preventing earlier presentation and better survival outcomes. BMC Medicine; 4 Aug 2022; DOI: 10.1186/s12916-022-02453-7
