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Prostate cancer: timing of therapy

Systematic review
Results
Comment

Arguments about cancer treatment are not just about what treatments to use, but when to use the treatments for best effect. There are several points in prostate cancer treatment where this question arises, one of which is in the case of locally advanced prostate cancer. A UK cancer registry showed that around 30% of new presentations of prostate cancer are locally advanced.

Treatment options include watchful waiting, hormone therapy, radical prostatectomy, or radiation with androgen deprivation. A new review [1] examined the evidence for use of hormonal therapy with LHRH agonists or antiandrogens with deferred treatment, when hormonal therapy was used after watchful waiting, radiotherapy, or prostatectomy.

Systematic review

The review used an extensive search strategy in a number of electronic databases to find randomised trials fulfilling the criterion of early versus deferred use of hormone therapy. The primary outcome of interest was overall mortality, with cancer mortality and cancer progression (overall, local and distant) as secondary outcomes.

Results

Eight trials were examined initially, though most results were calculated on seven, with about 6,900 men. All were randomised, and all but one open. Median follow up was typically five to eight years. A number of different hormonal regimens were used, with goserelin with or without flutamide being the most common, and with LHRH agonists featuring in most regimens.

Table 1 shows the results for overall mortality and cancer mortality. There was a significant reduction in mortality associated with early treatment in both cases, and with a similar number needed to treat to prevent one death of about 14. While mortality rates varied between the trials, the reduction in mortality associated with early hormonal therapy was consistent (Figure 1).



Table 1: Results for all-cause mortality and cancer mortality



Percent with
Outcome
Early
treatment
Deferred
treatment
Relative benefit
(95%CI)
NNTp
(95% CI)
All-cause mortality
37
45
0.86 (0.82 to 0.91)
13 (10 to 18)
Cancer mortality
16
23
0.71 (0.64 to 0.78)
14 (11 to 19)




Figure 1: Cancer mortality with early and deferred hormone treatment





In addition to mortality, there were similar reductions of about 30% in rates of overall, local, and distant disease progression.

Comment

This appears to be a solid result from a large number of patients studied over many years, and reporting an important, though not the only important, outcome of mortality. The average age of men in these trials was about 70 years at baseline, and relatively high mortality rates are to be expected over five to seven years. Early hormone versus deferred hormone treatment reduced mortality. It is another brick in the wall, allowing oncologists and urologists better to plan treatment of prostate cancer.

References:

  1. G Boustead, SJ Edwards. Systematic review of early vs deferred hormonal treatment of locally advanced prostate cancer: a meta-analysis of randomized controlled trials. BJU International 2007 Epub March 6 (doi:10.1111/j.1464-410X.2007.06802.x)

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