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Mason What clinicians should want from scientists

observations: rendered relatively meaningless in this context.

1. Very few patients, of the sort selected for this trial, Turning to a different category of prostate cancer,
die of prostate cancer, a least over a 10 year period. locally advanced disease (where the cancer has
It should be stressed that the patients in this trial spread beyond the capsule of the gland, or into
had early, localised disease, apparently confined to the adjacent seminal vesicles, but no metastatic
the prostate (categorised as stage cT1-2, N0, M0). spread), the prevailing clinical bias was different.
Prostate cancer-specific survival rates in all 3 arms Early studies had already shown that, in the context
of the trial were 99%. of “old fashioned” radiotherapy, outcomes were
less good than for localized disease. In retrospect,
2. The outcomes after surgery and radiotherapy many patients who were then labelled as “locally
were the same, and both treatments were roughly advanced” might today be recognised as having still
equivalent in the degree to which their side effects more advanced disease. The pivotal study by the
affected quality of life. European Organisation for Research and Treatment
of Cancer (EORTC) showed that the addition of ADT
[8]
3. However, more patients managed by active to radiotherapy substantially improved survival , but
monitoring suffered progression of their disease, it left an open question about the role of radiotherapy.
including the subsequent development of metastatic Nihilists argued that patients with locally advanced
disease, though this has not, yet, translated into a disease actually had occult metastatic disease, and
worsening of their 10-year overall survival rate. It that the important modality was the ADT. This was
should also be stressed that, although the numbers refuted in two randomised trials, of similar design,
progressing after active monitoring were double the in which patients with - predominantly - locally
numbers after surgery or radiotherapy, the absolute advanced disease (some had high risk localised
excess was only of the order of 4%. disease) were randomly allocated to ADT alone, or
to ADT plus radiotherapy [9,10] . These trials showed
Looking at the patients who died of prostate cancer, unequivocally that radiotherapy - a locally directed,
potentially curative treatment, improved survival.
one might reasonably expect to have been able to pick This probably means that some patients with locally
them out retrospectively, based on the conventional advanced disease can be cured with local treatment.
clinical parameters of tumor stage, prostate-specific Moreover it means that as a group they do, indeed,
antigen level, and Gleason grade. Unfortunately, such “need” to be cured - but we should not forget that other
complacency would be misplaced. For example, of 17 explanations leading to improved survival without
patients who died of prostate cancer, 8 had Gleason “cure” are not impossible.
scores of 6 at diagnosis, and 9 had scores > 7. The
numbers are very small, and some patients with After more than two decades, we can begin to answer
apparently Gleason 6 could have had more aggressive Whitmore’s questions: for patients with early prostate
tumors missed due to sampling errors, some of which cancer, cure is apparently not necessary in many
might have been identified on modern imaging such cases, at least over a 10-year period. Our dilemma
as multi parametric magnetic resonance imaging, is now that, though we know that this does not apply
which among other things is capable of detecting to all such men, we do not know how to identify the
anterior tumors that might not have been biopsied in all-important minority of such men who do need
this cohort. Even so, it seems inconceivable that these treatment. Two other studies, previously published,
clinical parameters, which we use to stratify patients have randomised patients to surgery, or to “watchful
into “low”, “intermediate”, and “high” risk groups, are waiting” [11,12] . The Swedish study reported improved
sufficient to enable us to determine which patients with survival with surgery, but the benefits appear to be
early prostate cancer need treatment, and which ones restricted to patients under 65 years of age. The
do not. This is a major, and urgent clinical priority - American study showed no evidence of a survival
solving it would, among other things, revolutionise the benefit overall, though suggested some benefit in
approach to prostate cancer screening. As described some men in a higher risk category. In contrast, the
by Maitland in an accompanying answer in this themed studies of locally advanced disease not only show that
issue, the scientific answer to the question of how to this category of disease is both life-threatening and yet
distinguish tigers and pussy cats will not come from curable, but they also point to a category of disease
cell lines, but will require a combination of biobanking which is deserving of more basic scientific attention
of tissues from patients with early prostate cancer, than perhaps it has had. All these studies carry the
combined with meticulous collection of associated same implication: the need for better biomarkers
clinical outcome data. Without the latter, the former are to enable us better to stratify patients. To test this
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ November 17, 2017 273