TO WATCH OR TREAT?

That is again the question.

You might have heard this, or not. It was big news and yet it was not. After years of slaying the beast of PSA screening that was conjured up as over treatment and harm, the swallows once again came back to their nests.

If one looks at it objectively and without bias, one finds a disdain for early intervention. But why if it saves lives. And now we have a formal basis to declare that PSA screening followed by surgical intervention saves lives. 

Had they taken the Tyrol regional (Western Austria) study to heart, a place where free healthcare is the norm and everyone gets a PSA screening followed by definitive treatment, the conclusions drawn were: “In the Tyrol region where treatment is freely available to all patients, where widespread PSA testing and treatment with curative intent occurs, there was a reduction in prostate cancer mortality rates which was significantly greater than the reduction in the rest of Austria. This reduction in prostate cancer mortality is most probably due to early detection, consequent down-staging and effective treatment of prostate cancer.”

Now comes data from the latest ProtecT Trial study that accrued 82,429 men aged between 50 to 69 years. 2,664 (3.2 percent) had clinically localized prostate cancer. 1643 were randomized. Cancer specific deaths included 8 in the “watchful waiting” group, 5 in the Surgical intervention arm and 4 in the Radiation therapy arm. Progression of disease was noted as follows:

112 patients in the “watchful waiting” group (or 22.9 events per 1,000 person-years). 46 in the surgery group. 46 in the Radiation group.“All cause mortality” deaths from any cause were equal in all three groups: 59 in the active monitoring group. 55 in the surgery group. 55 in the EBRT group. (The difference in the rates of all-cause mortality was not statistically significant (P = 0.87).

An interesting data from the trial revealed that:

27 men would have needed immediate initial surgery as opposed to initial active monitoring to avoid 1 case of metastatic disease

9 men would have needed immediate initial treatment (with surgery or EBRT) as opposed to active monitoring to avoid 1 case of clinical progression.

The question raised is of consequence to the lives of the many. Was the “watchful waiting” a science driven enterprise of empiricism or a pseudoscientific undertaking of tortured probabilities to prove that “Less is more” resource utility? A question that should haunt the experts at some level.

The Editorial on New England Journal of Medicine by Anthony D’Amico, MD PhD caught my attention. Now that the cat is out of the bag, even now there are statements that trouble the mind; for instance…”Therefore, if a man wishes to avoid metastatic prostate cancer and the side effects of its treatment,3 monitoring should be considered only if he has life-shortening coexisting disease such that his life expectancy is less than the 10-year median follow-up of the current study.” This sentence lends itself to further scrutiny, “if a man wishes to avoid metastatic prostate cancer and the side effects of its treatment, monitoring should be considered…” What does the author/doctor who wrote this think? The patient’s response as, “No sir I do not wish to avoid the dastardly effects of the malignancy and the necessitated treatment of the said metastatic disease?”

A sort of cover is also used here implying the following, “However, the increasing use of surveillance is already of potential concern, considering that men enrolled in PIVOT had a shorter life expectancy owing to coexisting disease than men of similar age entered into the Surveillance, Epidemiology, and End Results database.” In other words using PSA screening in these patients with co-morbidities lends itself to a potential bias in favor for the surgical side. True we need to use the modalities of treatments judiciously and with care to represent in the best interests of the patient.

In the end, however, the author goes on to say, “First, men assigned to active monitoring were significantly more likely to have metastatic disease than those assigned to treatment (P=0.004 for the overall comparison), with an incidence that was more than twice as high (6.3 per 1000 person-years vs. 2.4 to 3.0 per 1000 person-years). There was also a trend toward decreased death from prostate cancer among men assigned to surgery (hazard ratio, 0.63; 95% confidence interval [CI], 0.21 to 1.93) or radiation and androgen-deprivation therapy (hazard ratio, 0.51; 95% CI, 0.15 to 1.69) versus active monitoring.” 

Reasonable people make reasonable assumptions and thus reasoned judgment is called into play. The PSA screening tool is a worthwhile endeavor especially when conjugated with surgical intervention, as the Tyrol data from 2008 shows  and the current ProtecT Trial seems to suggest. Screening and early intervention improves people’s lives. Although Disease specific mortality is lowered the all cause mortality is not. A consideration here might be the age and co-morbid states of the population under study? You might argue about “All cause mortality” and “disease specific mortality” here but anyway you look at it the answer just stares back at you, defiantly.

So is PSA Screening a good thing? Answer: Yes.
Is Definitive surgical intervention in Early Prostate Cancer vs. "watchful waiting" a good thing? Answer: Yes.
Both answers appear accurate to date, unless you have extricated yourself from the predicate of being mortal. In that case, you might assign yourself the throne of a consultant expert and beam down guidelines to the plebeians.

REFERENCES:

1. Treatment or Monitoring for Early Prostate Cancer. Anthony V. D’Amico, M.D., Ph.D
http://www.nejm.org/doi/full/10.1056/NEJMe1610395#t=article

2. http://www.forbes.com/forbes/welcome/?/sites/benjamindavies/2016/09/14/prostate-cancer-screening-trial-shows-psa-screening-works-sort-of/&toURL=http://www.forbes.com/sites/benjamindavies/2016/09/14/prostate-cancer-screening-trial-shows-psa-screening-works-sort-of/&refURL=https://www.google.com/&referrer=https://www.google.com/

3. Bartsch, G et al. Tyrol Prostate Cancer Demonstration Project: early detection, treatment, outcome, incidence and mortality. BJU Int. 2008 Apr;101(7):809-16 http://www.ncbi.nlm.nih.gov/pubmed/18321314