The Unintended Burden of Increased Prostate Cancer Detection Associated With Prostate Cancer Screening and Diagnosis

doi:10.1016/j.urology.2009.08.078

Urology

Volume 75, Issue 2, February 2010, Pages 399-405

https://doi.org/10.1016/j.urology.2009.08.078 Get rights and content

The increasing incidence of prostate cancer is associated with the intensity of screening for prostate-specific antigen. Although some men may benefit from the early detection of prostate cancer through screening, all men diagnosed with prostate cancer experience an effect on their mental and physical well-being and that of their families. In light of the recent publication of the United States Preventive Services Task Force recommendations concerning prostate-specific antigen testing, this article reviews the quality-of-life implications of prostate cancer screening and diagnosis, and explores risk reduction in screened men as a potential strategy to manage these issues.

Section snippets

Trends in Prostate Cancer Diagnosis

Testing for PSA often leads to the early detection of prostate cancer. Unfortunately, because of its relatively high sensitivity and low specificity, the PSA test has caused many men to undergo a transrectal ultrasound and prostate biopsy. As a consequence, the introduction of PSA testing has increased the number of new cases dramatically. The effect of PSA testing on prostate cancer mortality is less clear.³ The recently reported Prostate, Lung, Colon and Ovarian (PLCO) trial reported no

Diagnosis- and Decision-Related Distress

The process of prostate cancer screening and performance of diagnostic procedures can have a negative effect on mental well-being. Men may experience anxiety throughout the screening process, with the wait for biopsy results being a particularly stressful event.¹⁸ A positive diagnosis can lead to further distress. For example, among 52 men who were enrolled in the ERSPC trial, mental health declined 1 month after diagnosis, returning to prediagnosis levels by 7 months.¹⁹

When given the news that

Effect of Prostate Cancer on a Patient's Family Members or Partner

Prostate cancer affects not only on the patient but also his close family members, particularly his spouse or partner, who may be his main source of support and who plays a significant role in the decision regarding treatment options.⁴² Research indicates that spouses may experience greater psychological and emotional distress than the patient.⁴³ When considering treatment options, spouses may not place the same emphasis as patients on the potential QOL effect of treatment side effects. To

Potential Ways to Minimize the Unintended Consequences of PSA Testing

Advancing technology has enabled the detection of prostate cancer at an earlier stage, before clinical symptoms arise. This offers the opportunity to treat tumors earlier and the potential to reduce the mortality, morbidity, and deterioration of psychosocial function that are associated with advanced prostate cancer. However, repeated PSA testing has led to the diagnosis of a large number of small-volume low-grade cancers that may never become clinically relevant. This problem is destined to

Reducing the Risk of Prostate Cancer

The high prevalence and latent nature of most prostate cancers, and the significant morbidity and mortality associated with prostate cancer treatment, make it a suitable candidate for a risk-reduction strategy. A successful risk-reduction therapy would reduce both morbidity and mortality from this disease. Furthermore, it would decrease the number of men and their families burdened with diagnosis, facing treatment options, and living with the anxiety and adverse events associated with

Conclusions

Widespread testing for PSA has dramatically increased the number of men diagnosed with prostate cancer. The unintended consequence of this practice has been the increasing numbers of men diagnosed with small-volume, low-grade disease that in most cases is not clinically significant. The cost to the patient and society is significant. Men who have undergone primary screening because of an elevated PSA are at high risk of being diagnosed with prostate cancer and may benefit from drug therapy

Acknowledgments

The author thanks Choice Pharma (Hitchin, UK) for providing medical writing support during the preparation of this article, with the support of GlaxoSmithKline.

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The cores are obtained from the peripheral zone of the prostate, which has the highest chance of harboring malignancy. For each core, the most common pattern of cancer is assigned a Gleason grade1–5 and similarly the second most common pattern is also assigned a Gleason grade. The sum of the most and second most common pattern grades is called the Gleason score.
Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: A prospective study of 1,962 cases
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The PSA era has witnessed dramatic shifts in how prostate cancer is diagnosed and treated. However, during the last 25+ years, the debate over PSA screening has intensified as more men undergo biopsy, many are diagnosed with indolent disease, and the majority undergo treatment and experience deleterious short-term and long-term complications.18,19 Better biopsy techniques, more sensitive PSA testing and lower serum PSA thresholds for prostate cancer detection have exacerbated this problem.
The detection of prostate cancer relies primarily on abnormal digital rectal examination or increased serum prostate specific antigen concentration. However, low positive predictive values result in many men with increased prostate specific antigen and/or suspicious digital rectal examination having a negative biopsy. We investigated the value of the PCA3 (prostate cancer gene 3) urine test in predicting the likelihood of diagnosis of cancer before biopsy.
We performed a prospective, community based clinical trial to evaluate PCA3 score before any biopsy. This trial was conducted at 50 urology practices in the United States. Samples were obtained from 1,962 men with increased serum prostate specific antigen (greater than 2.5 ng/ml) and/or abnormal digital rectal examination before transrectal prostate needle biopsy. Study samples (urinary PCA3 and biopsies) were processed and analyzed by a central laboratory. Sensitivity-specificity analyses were conducted.
A total of 1,913 urine samples (97.5%) were adequate for PCA3 testing. Of 802 cases diagnosed with prostate cancer 222 had high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation and were suspicious for cancer, whereas 889 cases were benign. The traditional PCA3 cutoff of 35 reduced the number of false-positives from 1,089 to 249, a 77.1% reduction. However, false-negatives (missed cancers) increased significantly from 17 to 413, an increase of more than 2,300%. Lowering the PCA3 cutoff to 10 reduced the number of false-positives 35.4% and false-negatives only increased 5.6%.
Urinary PCA3 testing in conjunction with prostate specific antigen has the potential to significantly decrease the number of unnecessary prostate biopsies.
Prostate cancer awareness and screening among male public servants in Anambra state, Nigeria
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Logically, it would be expected that early detection should lead to a reduction in cancer-related mortality as seen in other genitourinary tumors such as testicular cancer, but this is not the case with PCa [2]. In Nigeria, like other developing countries in sub-Saharan Africa, there is no national cancer mortality database or active screening program [3], which makes it difficult to assess the true burden of PCa. However, studies in Nigeria emphasize the increasing prevalence of the disease [4,5].
Early detection of prostate cancer (PCa) with prostate-specific antigen (PSA) has led to a stage migration with increased detection of early stage, potentially curable disease. Knowledge about PSA screening for PCa among men will lead to increased detection of potentially curable disease.
Male public servants in Anambra State, Southeast, Nigeria, were invited to complete a self-administered questionnaire on their knowledge of PCa and PSA screening. Results were analyzed using Microsoft Excel^® 2007.
A total of 652 men completed the questionnaire. Their mean age was 45.1 years (range 20–69). Overall, 74.1% of the respondents were aware of the existence of PCa, while 76.1% were able to identify one or more symptoms of the disease. Difficulty in passing urine was identified as the most common presenting symptom by 45.3% of the respondents, while 87% were able to identify risk factors for PCa. Whereas 56.7% were aware of PSA screening and 92% expressed interest in having PCa screening if recommended only 6.4% had undergone PSA screening in the preceding year.
Despite a high awareness of PCa among public servants in Anambra State, Nigeria, a very small proportion of these men had undergone PSA screening. To achieve a stage migration in PCa detection in Nigeria, early detection using PSA screening should be actively driven by health personnel using the media.
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Most clinically approved biomarkers of cancer are glycoproteins, and those residing on the cell surface are of particular interest in biotherapeutics. We report a method for selective labeling, affinity enrichment, and identification of cell-surface glycoproteins. PC-3 cells and primary human prostate cancer tissue were treated with peracetylated N-azidoacetylgalactosamine, resulting in metabolic labeling of cell surface glycans with the azidosugar. We used mass spectrometry to identify over 70 cell surface glycoproteins and biochemically validated CD146 and integrin beta-4, both of which are known to promote metastatic behavior. These results establish cell-surface glycoproteomics as an effective technique for discovery of cancer biomarkers.
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It is not easy to predict at which follow-up period the NNT will stabilise. Furthermore, since NNT in prostate-cancer screening mainly reflects the risk of over-diagnosis, it is not easy at this point to make estimates of this risk but it is probably not as high as some have feared,39 at least if screening is restricted to the age groups included in this study. As many as 314 (30%) screening attendees were in active surveillance at last follow-up in this study.
Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world. One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate.
In December, 1994, 20 000 men born between 1930 and 1944, randomly sampled from the population register, were randomised by computer in a 1:1 ratio to either a screening group invited for PSA testing every 2 years (n=10 000) or to a control group not invited (n=10 000). Men in the screening group were invited up to the upper age limit (median 69, range 67–71 years) and only men with raised PSA concentrations were offered additional tests such as digital rectal examination and prostate biopsies. The primary endpoint was prostate-cancer specific mortality, analysed according to the intention-to-screen principle. The study is ongoing, with men who have not reached the upper age limit invited for PSA testing. This is the first planned report on cumulative prostate-cancer incidence and mortality calculated up to Dec 31, 2008. This study is registered as an International Standard Randomised Controlled Trial ISRCTN54449243.
In each group, 48 men were excluded from the analysis because of death or emigration before the randomisation date, or prevalent prostate cancer. In men randomised to screening, 7578 (76%) of 9952 attended at least once. During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer, resulting in a cumulative prostate-cancer incidence of 12·7% in the screening group and 8·2% in the control group (hazard ratio 1·64; 95% CI 1·50–1·80; p<0·0001). The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0·40% (95% CI 0·17–0·64), from 0·90% in the control group to 0·50% in the screening group. The rate ratio for death from prostate cancer was 0·56 (95% CI 0·39–0·82; p=0·002) in the screening compared with the control group. The rate ratio of death from prostate cancer for attendees compared with the control group was 0·44 (95% CI 0·28–0·68; p=0·0002). Overall, 293 (95% CI 177–799) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death.
This study shows that prostate cancer mortality was reduced almost by half over 14 years. However, the risk of over-diagnosis is substantial and the number needed to treat is at least as high as in breast-cancer screening programmes. The benefit of prostate-cancer screening compares favourably to other cancer screening programs.
The Swedish Cancer Society, the Swedish Research Council, and the National Cancer Institute.
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View all citing articles on Scopus

: Responsibility for opinions, conclusions, and interpretation of data lies with the author.

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Prostate CancerThe Unintended Burden of Increased Prostate Cancer Detection Associated With Prostate Cancer Screening and Diagnosis

Section snippets

Trends in Prostate Cancer Diagnosis

Diagnosis- and Decision-Related Distress

Effect of Prostate Cancer on a Patient's Family Members or Partner

Potential Ways to Minimize the Unintended Consequences of PSA Testing

Reducing the Risk of Prostate Cancer

Conclusions

Acknowledgments

Lancet Oncol

J Urol

Eur J Cancer

J Urol

J Urol

J Urol

Int J Radiat Oncol Biol Phys

Contemp Clin Trials

J Urol

J Urol

Cancer Facts and Figures 2007

An assessment of the diagnosed prevalence of diseases in men 50 years of age or older

Am J Manag Care

Prostate-specific antigen and prostate cancer: prediction, detection and monitoring

Nat Rev Cancer

Prostate-specific antigen best practice statement: 2009 update

Guidelines for the Early Detection of Cancer

Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement

Ann Intern Med

PSA testing: public policy or private penchant?

J Am Med Assoc

Psychological adjustment of men with prostate cancer: a review of the literature

Biopsychosoc Med

Mortality results from a randomized prostate-cancer screening trial

N Engl J Med

Screening and prostate-cancer mortality in a randomized European study

N Engl J Med

Prostate cancer screening in the prostate, lung, colorectal and ovarian (PLCO) Cancer Screening Trial: findings from the initial screening round of a randomized trial

J Natl Cancer Inst

The influence of finasteride on the development of prostate cancer

N Engl J Med

Prostate-specific antigen: a review of the validation of the most commonly used cancer biomarker

Cancer

A decision analysis of alternative treatment strategies for clinically localized prostate cancerProstate Patient Outcomes Research Team

J Am Med Assoc

Prostate Cancer
The Unintended Burden of Increased Prostate Cancer Detection Associated With Prostate Cancer Screening and Diagnosis