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.