In reading some of the recent reports on PCa decisions regarding “watchful waiting” and surgery, as well as the benefit of PSA, one seems to get confused. Let me examine just three recent papers:
1. The recent NEJM Scandinavia studies conclude[1]:
Extended follow-up confirmed a substantial reduction in
mortality after radical prostatectomy; the number needed to treat to prevent
one death continued to decrease when the treatment was modified according to
age at diagnosis and tumor risk. A large proportion of long-term survivors in
the watchful-waiting group have not required any palliative treatment.
This is a clear statement of substantial efficacy. Survival
is key and this Trial demonstrates it.
2. In a recent JAMA article the author’s state[2]:
Available evidence favors clinician discussion of the
pros and cons of PSA screening with average-risk men aged 55 to 69 years. Only
men who express a definite preference for screening should have PSA testing.
Other strategies to mitigate the potential harms of screening include
considering biennial screening, a higher PSA threshold for biopsy, and
conservative therapy for men receiving a new diagnosis of prostate cancer….
They continue:
Before 2009, conflicting observational data and 2 small
trials could not resolve this controversy.7- 9 Two large randomized trials
published in 2009 that were expected to provide definitive conclusions yielded
conflicting results. Therefore, the benefits and harms of prostate cancer
screening continue to be debated….Recent interest in more patient-centered care
emphasizes the importance of informing men about risks and benefits of PSA
screening. However, recent clinical practice guidelines provided conflicting
results..
The Trials referred to are the European and American Trials
I have analyzed before on several occasions. Both, in my opinion and based upon
my analysis, are flawed. The European Trial measured PSA much too infrequently
thus leading to high mortality and both used a threshold of 4.0 with no attention
to velocity, age, family history, or percent free. That is both Trials used a
1992 standards through a 2009 period. The standard had dramatically changed and
it was never reflected in the Trial data.
3. In an earlier NEJM articles the authors conclude[3]:
During the median follow-up of 10.0 years, 171 of 364 men
(47.0%) assigned to radical prostatectomy died, as compared with 183 of 367
(49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval
[CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points).
Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate
cancer or treatment, as compared with 31 men (8.4%) assigned to observation
(hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6
percentage points). The effect of treatment on all-cause and prostate-cancer
mortality did not differ according to age, race, coexisting conditions,
self-reported performance status, or histologic features of the tumor. Radical
prostatectomy was associated with reduced all-cause mortality among men with a
PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and
possibly among those with intermediate-risk or high-risk tumors (P=0.07 for
interaction). Adverse events within 30 days after surgery occurred in 21.4% of
men, including one death….Among men with localized prostate cancer detected during
the early era of PSA testing, radical prostatectomy did not significantly
reduce all-cause or prostate-cancer mortality, as compared with observation,
through at least 12 years of follow-up. Absolute differences were less than 3
percentage points.
This was a Veteran’s Department study. As such one must
consider, in my opinion, how they function as compared to a more conventional medical
establishment. The statements above do appear conflicting. On the one hand
mortality was 5.8% versus 8.4% in the two groups, favoring prostatectomy.
However the conclusions state that there is no difference in mortality.
How does a physician and patient interpret this data? The
U.S. Government conducted Trial in my opinion is problematic at best. The JAMA
result is one where we have on the one hand and on the other. The Scandinavian
study seems clear cut. Yet confusion still reigns.
This is why any study of comparative clinical effectiveness
is of dubious merit. The data is not available and the Trials are oftentimes
contradictory.
References
1. Bill-Axelson, A., et al, Radical Prostatectomy or Watchful
Waiting in Early Prostate Cancer, NEJM, March 6, 2014.
2. Hayes, J., M. Barry, Screening for Prostate Cancer With the
Prostate-Specific Antigen Test, JAMA. 2014; 311(11):1143-1149.
3. Wilt, T., et al, Radical Prostatectomy versus Observation for
Localized Prostate Cancer, NEJM, July 25, 2012.
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