Louis Denis
We know since 78 years that autopsy studies show a lot of preneoplastic
lesions (intraepithelial neoplasia) and micro foci of prostate cancer in the
peripheral zone of the organ. They can be found at the age of 30, increasing
with age to be found in about two thirds of all males at age 70.
These histological lesions are called latent if found on autopsy, incidental
when discovered at surgery and indolent in clinical practice.
These lesions became a clinical challenge when the pathologists started
looking for small volumes of cancer in resected tissue of periurethral
adenoma. Depending the number of histological cuts a new source of prostate
cancer, varying from 2 to 16% of patients, was discovered and subjected to a
clinical decision. A ten year epic discussion developed among urologists if
these lesions had to be treated as an early cancer or ignored as indolent
disease.
Consensus was found following the wisdom of H. Jewitt of Johns Hopkins to
divide these lesions according to volume. Stage A1 (T1a) was reserved for a
lesion smaller than 5% of the resected tissue and stage A2 (T1b) if more
than 5% of tissue was involved. The consensus was to follow the small
lesions and treat the bigger ones. For reflection 5% of 40 grams resected
tissue represents 2 grams (2 cc) of cancerous tissue.
The detection of up to 16% unsuspected cancer was confirmed by a clinical
study of 300 males subjected to open surgical biopsy. None of the 300 males
had LUTS symptoms and only nine cases out of 39 (13%) yielded suspicious
findings at rectal palpation (the famous Bowery series. Cancer7, 1954). It
was advised to precede definitive surgery by an open surgical biopsy through
a perineal incision.
The Swedish custom to search for cancer by fine needle aspiration relying on
cell ploidy is an excellent approach but could not convince clinical
practice due to its complexity. The subsequent public health result remains
the failure to detect localized prostate cancer resulting in a prostate
cancer population of locally advanced and/or metastatic disease. This
frustration situation came to an end in the late 1980’s with the
introduction of the PSA test as a monitoring marker of successful surgery
and the introduction of the biopty gun allowing multiple systemic blind
biopsies of the prostate volume. The presentation of the PSA test as a
useful, first line screening test by Catalona in the N Engl J Med in 1991
opened the gate for an avalanche of PSA tests and multiple derivatives or
gimmicks in the following decade. The use of the PSA test as an excuse to
biopsy going from the original six core biopsy to carpel biopsy revealed, no
surprise, an increase in incidence of indolent prostate cancer.
To make the situation more complex the AJJC and UICC TNM committees allowed
the introduction of a new stage prostate cancer T1c. This cancer is not
visible on imaging nor palpable and relies on the PSA test. Of course there
is no pathological T1 as pT2 is the minimum stage of the total surgical
specimen.
This simplistic clinical concept convinced some of the profession and some
of the public that prostate cancer mortality would decrease to zero if we
screened all males.
Now 20 years after we launched the European Randomized Study for Screening
of Prostate Cancer (ERSPC) it becomes clear that the PSA test is a good
marker in extreme values but lacks the capacity to distinguish indolent from
aggressive clinical prostate cancer. As demonstrated in the trial
overdetection and overtreatment in up to 50% of cases emphasized the harm
versus the advantages. These lessons of the past are complemented by the
wisdom of the past in using the slow clinical progression of prostate cancer
as an indication to forgo treatment if the patient has a limited life
expectancy of ten years. This is termed watchful waiting with no intent to
cure but to gain quality of life. Detecting small cancers and forgo curative
treatment is termed active surveillance and aims for cure if the indolent
tumor stays from the imposed limits of safety: stage, grading, low PSA and
PSA density, % of cancer in core biopsies, etc.
There are enough published results of delayed curative treatment for Europa
Uomo to put active surveillance as first choice in selected (+ 30%) cases of
newly diagnosed prostate cancer.
The better informed the easier for the patient and his family to realize
that this choice is rationale and overrides any negative expectations. The
patient education is a needed platform to recognize the uncertainties of
prostate cancer and enjoy his quality of life and lack of side-effects from
skipping invasive treatment.
It is a small risk but easily evaluated in the knowledge of uncertainties of
diagnosis and treatment. The discussion among professionals will be greatly
solved as soon as future research predicts the distinction of nature rather
than size of aggressive lethal cancers. In this domain conscious based
policy stands up against evidence based policy.