Influence of blood prostate specific antigen levels at age 60 on benefits and harms of prostate cancer screening: population based cohort study
BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g2296 (Published 28 March 2014) Cite this as: BMJ 2014;348:g2296
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
The article by Carlsson et al (1) suggests that at age 60, for men with PSA level <1ng/mL, no further screening is recommended and PSA more 2 ng/mL is beneficial, with PSA level of 1-2 ng/mL the decision is based on the discussion between patient and doctor. These guidelines are different from that of the American Cancer Society (2).
The American Cancer Society have given guidelines on the frequency of screening of prostate cancer using PSA. The guidelines do not clarify compulsory screening, but mention about consultation with the physician and after informed decision taken by the individual. The guideline says, “Assuming no prostate cancer is found as a result of screening, the time between future screenings depends on the results of the PSA blood test:
•Men who choose to be tested who have a PSA of less than 2.5 ng/ml, may only need to be retested every 2 years.
•Screening should be done yearly for men whose PSA level is 2.5 ng/ml or higher”.
The association of prostate cancer with higher levels of PSA is known. However, the difficulty lies in the identification of critical value of PSA. Should we consider 2 ng/mL or 2.5 ng/mL or 4 ng/mL (which is found to be higher risk of prostate cancer)? It has also been recommended that along with PSA, clinical digital rectal examination should also be done and it adds to detect prostate cancer at an early stage. We should also consider the false negativity of PSA at low levels and also false positivity at higher levels at 4 ng/mL which can lead to unnecessary biopsy of prostate leading to haemorrhage, pain and discomfort to the patient.
In the context of varying guidelines at present, and considering that PSA screening is useful, one should consider for screening with PSA if there is high risk factor such as familial history of prostate cancer, African-Americans, higher age more than 60 years. But dilemma still remains on the frequency and level of PSA to consider for re-screening for prostate cancer.
References
1. Carlsson S, Assel M, Sjoberg D, Ulmert D, Hugosson J, Lilja H et al. Influence of blood prostate specific antigen levels at age 60 on benefits and harms of prostate cancer screening: population based cohort study. BMJ 2014;348:g2296
2. American Cancer Society. Prostate Cancer: Early Detection. http://www.cancer.org/acs/groups/cid/documents/webcontent/003182-pdf.pdf (retrieved on 1.4.2014)
Competing interests: No competing interests
Definition of metastasis
At risk of being labelled as a pedantic, I have to disagree, with the use of the word 'metastasis' outside the context of its clinical definition.
Oxford dictionary defines metastasis as 'The development of secondary malignant growths at a distance from a primary site of cancer' (1) .
In clinical practice, the use of the word ’metastasis’ conforms to the Oxford dictionary definition. But in this paper, patients with high PSA (>100) seems to have been termed as having metastatic disease in the absence of any clinical or radiological evidence of metastasis.
Moreover, patients with ultra high PSA but without radiological evidence of metastasis can treated radically with good clinical outcome. For instance, Saskatchewan cancer registry reports that in patients with PSA of ≥ 100 ng/ml, Radiotherapy was associated with an excellent 5- and 10-year cause-specific survival of 80% and 54% (2). Patients with PSA >100 had a median time to biochemical progression of 88 months following radiotherapy in our limited case series (3). These excellent survival rates are certainly not comparable to the poor prognosis of patients with radiologically evident metastasis.
Could the authors clarify the number of patients labelled as having metastatic disease purely because of high PSA but without any clinical evidence of metastasis? A PSA >100 at diagnosis in the unscreened group is not necessarily an indicator of poor prognosis if there is no clinical or radiological evidence of metastasis. (4).
Overall the authors are to be congratulated for proposing and evaluating a novel strategy to minimise the risk of over diagnosis as well as increase the effectiveness of the PSA screening in prostate cancer. External validation of their strategy in an independent group would make an important difference to the de facto PSA screening programme.
References
1. Definition of metastasis in English: Oxford Dictionaries. [Internet]. [cited 2014 Mar 31]. Available from: http://www.oxforddictionaries.com/definition/english/metastasis
2. Rodrigues G, Bae K, Roach M, Lawton C, Donnelly B, Grignon D, et al. Impact of ultrahigh baseline PSA levels on biochemical and clinical outcomes in two Radiation Therapy Oncology Group prostate clinical trials. Int J Radiat Oncol Biol Phys. 2011 Jun 1;80(2):445–52.
3. Walker GA, Perry CJ, Sundar S. Radical prostate radiotherapy to M0 patients with a presenting PSA of more than 100. ESTRO 31. European Society for Radiotherapy & Oncology Annual meeting. Barcelona: Radiotherapy and Oncology 2012.; p. S431.
4. Carlsson S, Assel M, Sjoberg D, Ulmert D, Hugosson J, Lilja H, et al. Influence of blood prostate specific antigen levels at age 60 on benefits and harms of prostate cancer screening: population based cohort study. BMJ. 2014 Mar 28;348(mar28 1):g2296–g2296.
Competing interests: No competing interests
Carlsson et al make a valuable contribution to defining the benefits of PSA screening in terms of Prostate Cancer deaths avoided. The NNT to avoid a prostate cancer death seems very favourable.
But although they repeatedly mention high cost, and harm such as overdiagnosis, I could not find the key information I as a patient would need to make a decision for or against screening.
I would want to know not only my (improved) chance of avoiding a death from prostate cancer, but also what chance of suffering harm (such as death from unnecessary biopsy, infection, surgery etc.). A statement of overall crude mortality would encompass these concerns, but I could not find it anywhere in the article. And this despite their statement that "copy of the cause of death certificate was obtained for men who had died, and an independent blinded review committee determined the cause of death for men with a diagnosis of prostate cancer. Participants who emigrated or died of other causes were censored at the date of emigration or death. Participants who did not die were censored at their last documented follow-up date for vital status or the study end date, 31 December 2010."
I would be very grateful if Carlsson et al provided the overall crude mortality and any subgroupings of interest.
Competing interests: Harms vs Benefits !
Re: Influence of blood prostate specific antigen levels at age 60 on benefits and harms of prostate cancer screening: population based cohort study
In this article, the authors concluded that continuing to screen men with PSA levels >2 ng/mL at age 60 is beneficial for reduction in prostate cancer mortality (percentage of the case in this study population was 28%). In addition, no further screening is recommended for men with a PSA level <1 ng/mL at age 60 (percentage of the case in this study population was not clear). All subjects who underwent annual health examinations at Health Evaluation and Promotion Center, Tokai University Hachioji Hospital are subjected to measure PSA level. In our facility, the average PSA was 1.47 ng/dL for men aged 60 (n=1,729); 869 subjects (50%) had a PSA level <1 ng/dL, 530 subjects (31%) had a level equal to or more than 1 ng/dL but less than 2 ng/dL, and 330 subjects (19%) had ≥2 ng/mL.
According to the same criteria for classification in this study, 19% subjects, which was 9 points less than that of this study, needed to be screened every year, while 50% subjects may not need further screening in our facility. However, further study will be necessary if this is the case, since the percentage of subjects with a PSA level ≥2 ng/mL varied and it is a possibility that this cutoff value may not be suitable for Japanese subjects.
The Japan Society of Ningen Dock has been constructing a database for one million five hundred thousand Japanese subjects and we are going to verify whether this is the case.
Competing interests: No competing interests