Recommendations on screening for prostate cancer with the prostate-specific antigen test

In 2014 the Canadian Task Force for Preventative Medicine reported in your journal that, for prostate screening "the harms outweigh the benefits" (1). In addition, it was recently reported that pathological differentiation of insignificant prostate cancer in the early stages can be inaccurate, compounding the harms (2). We propose there may be a common denominator underlying both issues.

In breast cancer, needle biopsies increase the likelihood of cancer cell spreading by 50% over women that had immediate surgical removal of the tumor (3) Also, radical prostatectomy reduces mortality among men with localized prostate cancer (4). Prostate biopsies may take 12 or more needles. This results in significant damage to an organ as small as a walnut. For most patients this inflammatory period causes no lasting problems and residual dormant prostate cancer cells remain dormant, in some patients it may be problematic. Dormant cancer cells carrying epidermal growth factor (EGF) related surface receptors such as Her2 may become aggressive during the wound healing inflammation. Thus an association between benign prostate cancer, inflammation and high-grade prostate cancer has already been noted (5).

Trauma induces many growth factors including EGF, Heparin-binding (HB - EGF, Nerve growth factor (NGF) among many others. These factors can stimulate growth and migration behavior of cells carrying the appropriate receptors. This is supported by the higher incidence of Her2 and EGFR positive expression in metastatic prostate cancer compared to primary cancer 6-8). Also, in receptor positive patients the initial biopsy analysis (2) may have correctly identified non-aggressive cancer that became subsequently activated during the wounding. Thus, at prostatectomy, these tumors would be found to have progressed, resulting in an apparent inaccurate initial diagnosis.

Finally, a reduction in breast cancer relapses has been observed with perioperative non-steroidal anti-inflammatories (9). Such drugs may also be effective when used during injury recovery after biopsies.

References

1.Cancer Research UK, Screening for Prostate Cancer, 2014.

2.Sonn GA, Natarajan S, Margolis DJA, et al. Targeted Biopsy in the Detection of Prostate Cancer Using an Office Based Magnetic Resonance Ultrasound Fusion Device. J Urol 2013; 189: 86-92.

3.Hansen NM, Xing Ye, Baiba J, et al. Manipulation of the primary breast tumor and the incidence of sentinel node metastases from invasive breast cancer. Arch Surg 2004; 139: 634-640.

4.Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2005; 352:1977-84.

5.Gurel B, Lucia MS, Thompson IM Jr. et al. Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev 2014; 23: 847-56.

6.Carlsson J, Shen L, Xiang J, et al. Tendencies for higher co- expression of EGFR and HER2 and downregulation of HER3 in prostate cancer lymph node metastases compared with corresponding primary tumors. Oncol Lett 2013; 5; 208-214.

7.Di Lorenzo G, Tortora G, D'Armiento FP, et al. Expression of epidermal growth factor receptor correlates with disease relapse and progression androgen-independence in human prostate cancer. Clin Cancer Res 2002; 8: 3438-3452.

8.Carles J, Lloreta J, Salido M, et al. Her-2/neu expression in prostate cancer: a dynamic process? Clin Cancer Res 2004; 10: 4742-4745.

9.Retsky M, Demicheli R, Hrushesky WJ, et al. Reduction of breast cancer relapses with perioperative non-steroidal anti-inflammatory drugs: a new finding. Curr Med Chem 2013: 20; 4163-76.

Conflict of Interest:

None declared

I refer to the article published in the CMAJ of November 4 2014. Vol.186. I was shocked and saddened to read your article on this important test. Why on earth do we always have to go back to the start in medicine. Is it the need to be seen publishing something , because I just cannot believe that any body would come up with such a ridiculous , short sighted and in my view , irresponsible recommendation. The PSA test and more so ,serial testing of PSA, is a valuable and essential clinical test. It is what is being done with the information once a problem was identified, where the harm might be done. Dr E R Snyman. Camrose, Alberta

Conflict of Interest:

None declared

I am deeply disappointed with the recommendations of the task force on the use of the PSA test as a screening test for cancer. I am a seventy nine year old man and an example of a patient in whom the PSA test was clearly beneficial.

For reasons unrelated to the PSA test, I changed my family physician (FP) in 2013. Although I was symptomless my new FP ordered the PSA test in February 2014 (it had not been done previously) and found it to be very high (41 ng/ml). Biopsy revealed an aggressive form of cancer of the prostate (Gleason grade 9) and CT scan showed pelvic lymph nodes. Bone scan was negative for metastases. I am now on anti-androgen medication and the cancer is in remission.

If my former FP had carried out PSA testing my cancer might have been detected before the cancer had spread to the lymph nodes hence been potentially curable. I am disappointed that he did not discuss with me the pros and cons of the PSA test and took it upon himself to make that decision without consulting me. I am thankful that my new FP ordered the test.

The problem is not with the PSA test itself; it is with the way the test results are interpreted and managed. Clearly, interventions such as biopsy, prostatectomy and radiotherapy are potentially harmful hence it is not appropriate to carry out such procedures on a man with low probability of a lethal condition.

I plead for continued use of the PSA test, open discussion with patients about the interpretation of the results and more use of watchful waiting in men whose test results are equivocal.

Conflict of Interest:

None declared