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Murray Primary circulating prostate cells

bone, over a variable time period. avoiding unnecessary biopsies is a worthwhile aim if it
does not prejudice the number of clinically significant
Two large questions have yet to be answered: (1) cancers detected.
what is the role of prostate cancer screening? (2)
what treatment is appropriate for men diagnosed with Active surveillance is a recognized initial treatment
prostate cancer? An ideal prostate cancer screening option for men with early stage low-grade prostate
test would not detect all prostate cancers, but only cancer. The option to delay or avoid definitive
those prostate cancers which have the potential to therapy avoids or minimizes patient morbidity without
cause harm to the patient. At present, the only widely compromising long-term outcomes in appropriately
used screening test is serum total prostate-specific selected patients. [10,11] According to the Prostate Cancer
[12]
antigen (PSA), which in a range of 4-10 ng/mL is Intervention Versus Observation Trial, men with low
associated with a positive biopsy rate for all cancers risk disease (defined as a PSA ≤ 10 ng/mL, a Gleason
of approximately 30%. of which it has been estimated score ≤ 6, and T stage 1 or 2a) had no difference
[1]
that 23-42% of screen detected prostate cancers are in all-cause mortality and prostate cancer-specific
over treated. Men with clinically insignificant prostate mortality, or in rate of progression to bony metastasis,
[2]
cancers who were never destined to have symptoms when assigned to radical prostatectomy or to active
or altered life expectancy may not benefit from knowing observation. The criteria for active observation (AO)
that they have the “disease.” The detection of clinically according to Epstein et al. are a diagnosis of prostate
[13]
insignificant prostate cancer may be considered an cancer, with three or fewer of the 12 prostate biopsy
adverse effect of the prostate biopsy. cores positive for cancer. That no single biopsy core
with > 50% infiltration and a PSA density < 0.15 ng/mL.
Screening for prostate cancer remains controversial. Using these criteria to select patients with “insignificant
The two large studies published in the United States disease” has a positive predictive value of 95% and
and Europe produced different results; [3,4] as a a negative predictive value of 66%. These men
[14]
consequence, the American Urology Association are actively followed up with repeat annual biopsies.
guidelines do not recommend screening in men The timing of intervention after the initial diagnosis is
over 70 years or in those with less than 10 years’ based on variables such as PSA kinetics, Gleason
life expectancy. However, they recognize that grade progression, patient preference, and clinical
[5]
some elderly men who are healthy may benefit from or radiologic evidence of disease progression. [10,15]
screening. Why the controversy? Presently, a new An increase in the Gleason score at repeat biopsy is
diagnosis of prostate cancer is nearly always in men predictive of the time to active treatment and correlates
with an elevated screening serum total PSA who have with patient outcome. It has been reported that
[16]
been referred for a prostate biopsy. Serum total PSA Gleason score progression occurs in approximately
is prostate specific. However, it is also increased in 20% of men, with more than 50% of cases occurring
benign diseases such as hyperplasia and prostatitis. [4,5] within two years of the initial diagnosis. However, a
[17]
In fact, 10-20% of men aged 50 years and 70 years similar increase is seen in men subjected to immediate
will have a raised PSA, but only 25% of those with a repeat biopsy when entering an AO program. This
[18]
serum total PSA of 4-10 ng/mL will be found to have a short time interval, when compared with the long natural
biopsy positive for cancer. Moreover, the frequency history of prostate cancer, suggests that sampling error
[6]
of men with an elevated PSA and benign biopsy is rather than tumor progression is probably the primary
country dependent and may be significantly different source of tumor upgrading in these men.
[7]
between rural and metropolitan populations in the
same country. [8] The use of other biomarkers, such as circulating
prostate cells (CPCs), could be useful in re-categorizing
To complicate matters further, not all prostate cancers the patients who could be more adequately treated
need treatment. It has been estimated that 23-42% of by active surveillance. One such biomarker could
screen-detected prostate cancers are over treated. be circulating tumor cells, or, in the case of prostate
[2]
For every 100 men with an elevated PSA between cancer, CPCs. We review the literature on circulating
4 ng/mL and 10 ng/mL, only about 14 will have a tumor cells both to try to answer the question of whether
clinically significant prostate cancer detected. Eighty- they could be clinically useful to detect prostate cancer
six will undergo a biopsy, with its associated risks, for and as a guide to initial treatment, observation, or
what is found to be a benign disease. Infection and active treatment. We review the process of cancer cell
hemorrhage are the main potentially serious side dissemination from the primary tumor and how this
effects of prostate biopsy, with a 30-day complication may affect cell markers, and thus determine the criteria
rate of 3.7%, especially in older patients. Therefore, for detecting or identifying circulating tumor cells.
[9]
454 Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ December 16, 2016