Screening for Prostate Cancer

Introduction

Prostate cancer is cancer of the prostate gland, part of the male reproductive system. It is the second most common type of cancer in men worldwide.

In 2012, the United States Preventive Services Task Force published guidelines recommending against screening for prostate cancer [1]. These recommendations were in contraindication to earlier guidelines, and generated a significant debate both in the medical and non-medical community. [2][3]

Incidence and Risk Factors

The lifetime risk of prostate cancer diagnosis is 16% and the lifetime risk of death is 2.8%. Prostate cancer is rare before age 50, and few men die before age 60 [1]. Prostate cancer is more common in African-Americans and Hispanics. Furthermore, the age of onset in African-Americans is earlier, and the cancer is more aggressive.

There is a twofold increased of prostate cancer in patients that have at least one first degree relative with prostate cancer. This risk increases with a greater number of family members. Genetics also plays a role in development of prostate cancer. Patients with BRCA1/BRCA2 and Lynch syndrome have higher risk of prostate cancer. Smokers have a higher risk of prostate cancer.

Cost to US health care systems

In the USA, the total estimated expenditure on prostate cancer was 9.862 billion US dollars in 2006. The mean annual costs per patient in the USA were [4]:

  • $10,612 in the initial phase after diagnosis
  • $2134 for continuing care
  • $33,691 in the last year of life

Diagnosis and Early Detection of Prostate Cancer

Eighty percent of men diagnosed with prostate cancer undergo a biopsy because of a suspicious serum prostate specific antigen (PSA). Twenty percent of men have a prostate nodule detected during a digital rectal examination that prompts a biopsy.

Prostate Specific Antigen Test

PSA is a protein made by normal prostate cells. The detection of this protein, therefore, is not specific to prostate cancer. PSA may be elevated in any condition that leads to increased number of prostate cells (e.g. benign prostate hyperplasia), or any condition that leads to leakage of this protein from prostate cells (e.g., infections, trauma and even normal ejaculation).

The cutoff value for PSA used in screening for prostate cancer is 4.0ng/ml. This cutoff translates into [5]:

  • Sensitivity = 21%
  • Specificity = 91%
  • Positive Predictive Value (PPV) = 30%
  • Negative Predictive Value (NPV) = 85%

This test has poor discriminating ability between prostate cancer and benign prostate hyperplasia (BPH), [6] and PSA value may be elevated 5 to 10 years, or even earlier, before the cancer causes any symptoms. [7] Several attempts to improve the PSA test, such as by measuring PSA Velocity [8] or PSA Density [9], have not been found to be superior to standard PSA test.

In summary, the PSA test has a high false positive rate, and a negative test does not rule out the possibility of having prostate cancer.

Or, in other words [10]:

23 men need to be diagnosed with prostate cancer
18 men need to be treated for prostate cancer
To prevent one death

Consequences of PSA elevation

Most patients with elevated PSA will undergo a trans-rectal needle biopsy of the prostate gland. This biopsy is not a perfect gold standard and has a false negative rate of about 10–20%. Furthermore, prostate biopsy is not a benign procedure and may have many side effects, including [11]:

  1. Bleeding
  2. Infections that may lead to sepsis (and death)
  3. Urinary retention
  4. Anxiety

If the prostate biopsy is positive, then depending on a number of factors (histological grade of cancer, co-morbidities, metastases etc), men typically undergo surgery (most often radical prostatectomy), radiation therapy, or both. A subset of men may be monitored closely without any treatment.

Radical Prostatectomy has many of side effects, including [12]:

  • Urinary incontinence in 15% to 50%
  • Sexual dysfunction in 20% to 70%
  • Bowel problems
  • Operative mortality of 0.1% to 0.5%, which increases with age, especially for people over 75 years of age

Complications of radiation therapy include [12]:

  • Erectile dysfunction in 25% to 45%
  • Urinary incontinence in 2% to 16%
  • Bowel dysfunction in 6% to 25%

The Benefit to Risk ratio can be summarized by calculating the Number need to treat, and Number Needed to Harm [13]:

Number Needed to Treat to benefit = 0
Number Needed to Harm = 1 out of 5 patients who are screened

Prostate Cancer Screening Guidelines

Screening for Prostate Cancer: U. S. Preventive Services Task Force (USPSTF) Recommendation Statement

The USPSTF recommends against PSA based screening for prostate cancer. For high-risk populations, there is not enough data to recommend screening. [1]

The reduction in prostate cancer mortality after screening is very small, and the benefits do not outweigh the harms. The harms of screening include pain, fever, bleeding, infection, transient urinary difficulties associated with prostate biopsy, psychological harm of false positive results, and over-diagnosis.

American Cancer Society (ACS) for Early Detection of Prostate Cancer

The ACS recommends that asymptomatic men with at least a 10-year life expectancy have an opportunity to make an informed decision with their healthcare provider about screening for prostate cancer, after they receive information about the uncertainties, risks, and potential benefits associated with prostate cancer screening. [14]

The ACS observes that a good screening test does not exist, but still continues to recommend the PSA test with a cutoff value of 4.0 ng/ml for screening.

Early Detection of Prostate Cancer: American Urological Association (AUA) Guideline

The AUA’s major recommendations are age based. The do not recommend screening in patients less than 40 years of age, men of average risk less than 50 years of age, and men greater than 70 years of age. For men between 55–69, the AUA recommends shared decision-making. [15]

Screening for Prostate Cancer: A Guidance Statement from the Clinical Guidelines Committee of the American College of Physicians (ACP)

The ACP recommends that providers inform men age 50–69 years about the limited potential benefits and substantial harms of screening. They recommend that clinicians base the decision to screen for prostate cancer using PSA test based on patients risk of prostate cancer, life expectancy and preferences. [16]

Conclusion

Given the current research, all medical societies acknowledge that there is minimal benefit in screening the general population for prostate cancer, and there is a greater potential for harm.

All medical societies, except USPSTF, endorse shared decision making in people with high risk of prostate cancer, such as people with positive family history, African-Americans, genetic predisposition and other risk factors. The USPSTF guidelines discourage use of PSA test in all patients, and recommend discussion and shared decision-making only when the patients bring up the topic.


  1. Moyer, V. A. (2012). Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med, 157(2), 120–134.  ↩

  2. Gomella, L. G., Liu, X. S., Trabulsi, E. J., Kelly, W. K., Myers, R., Showalter, T. et al. (2011). Screening for prostate cancer: the current evidence and guidelines controversy. Can J Urol, 18(5), 5875–5883.  ↩

  3. Kaffenberger, S. D., & Penson, D. F. (2014). The politics of prostate cancer screening. Urol Clin North Am, 41(2), 249–255.  ↩

  4. Roehrborn, C. G., & Black, L. K. (2011). The economic burden of prostate cancer. BJU Int, 108(6), 806–813.  ↩

  5. Wolf, A. M., Wender, R. C., Etzioni, R. B., Thompson, I. M., D’Amico, A. V., Volk, R. J. et al. (2010). American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin, 60(2), 70–98.  ↩

  6. Meigs, J. B., Barry, M. J., Oesterling, J. E., & Jacobsen, S. J. (1996). Interpreting results of prostate-specific antigen testing for early detection of prostate cancer. J Gen Intern Med, 11(9), 505–512.  ↩

  7. Draisma, G., Boer, R., Otto, S. J., van der Cruijsen, I. W., Damhuis, R. A., Schroder, F. H. et al. (2003). Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst, 95(12), 868–878.  ↩

  8. Vickers, A. J., Savage, C., O’Brien, M. F., & Lilja, H. (2009). Systematic review of pretreatment prostate-specific antigen velocity and doubling time as predictors for prostate cancer. J Clin Oncol, 27(3), 398–403  ↩

  9. Catalona, W. J., Richie, J. P., deKernion, J. B., Ahmann, F. R., Ratliff, T. L., Dalkin, B. L. et al. (1994). Comparison of prostate specific antigen concentration versus prostate specific antigen density in the early detection of prostate cancer: receiver operating characteristic curves. J Urol, 152(6 Pt 1), 2031–2036.  ↩

  10. Welch, H. G., & Albertsen, P. C. (2009). Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986–2005. J Natl Cancer Inst, 101(19), 1325–1329.  ↩

  11. Stroumbakis, N., Cookson, M. S., Reuter, V. E., & Fair, W. R. (1997). Clinical significance of repeat sextant biopsies in prostate cancer patients. Urology, 49(3A Suppl), 113–118.  ↩

  12. UpToDate - Prostate Cancer Screening  ↩

  13. TheNNT.com, Prostate Specific Antigen (PSA) Test to Screen for Prostate Cancer  ↩

  14. Brooks, D. D., Wolf, A., Smith, R. A., Dash, C., & Guessous, I. (2010). American Cancer Society Guideline for the Early Detection of Prostate Cancer: Update 2010. J Natl Med Assoc, 102(5), 423–429.  ↩

  15. Carter, H. B., Albertsen, P. C., Barry, M. J., Etzioni, R., Freedland, S. J., Greene, K. L. et al. (2013). Early detection of prostate cancer: AUA Guideline. J Urol, 190(2), 419–426.  ↩

  16. Qaseem, A., Barry, M. J., Denberg, T. D., Owens, D. K., & Shekelle, P. (2013). Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med, 158(10), 761–769.  ↩