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and occurrence of metastasis could be eight years without any Recently, Wirth et al. reported the results of an interim analysis of the
Theoretically, the median time for clinical Early Prostate Cancer (EPC) programme, which consists of three
progression after biochemical relapse in the post-operative course is randomised, double-blind, placebo-controlled trials prospectively
five years, which supports a delayed treatment. As a result, designed for combined analysis.
In this programme, a total of 8,113
observation with delayed hormonal therapy for symptomatic or patients with localised or locally advanced prostate cancer were
metastatic disease can be one of the treatment options. randomised to a pure antiandrogen (bicalutamide 150mg/day) group
or a placebo group in addition to standard care including watchful
Nevertheless, the psychological impact of a rising PSA is important, and waiting, radical prostatectomy and radiation therapy. At
one must consider its effect on the quality of life of patients. In addition, a median 5.4 years of follow-up, bicalutamide was found to
in oncology it is always preferable to treat low tumour volumes. significantly enhance progression-free survival of radical
Another argument for immediate treatment is the fact that the five-year prostatectomy patients with locally advanced disease. Bicalutamide
metastatic-free survival rate was only 31% in patients who underwent provides a similar survival outcome to castration, including a bilateral
a biochemical relapse before two years or had a PSA doubling time <11 orchiectomy or LHRH agonist in previously untreated patients with
months or a Gleason score >7 or a seminal vesicle invasion based on a locally advanced prostate cancer, and confers a statistically significant
radical prostatectomy specimen. The PSA level at which hormonal benefit over castration with respect to sexual interest and physical
therapy should be initiated remains to be determined. Messing et al. capacity.
Another recent study comparing flutamide, another non-
compared immediate versus deferred androgen deprivation therapy steroidal antiandrogen, versus no adjuvant treatment also showed that
with surgical or medical castration by luteinising-hormone-releasing flutamide induced a better recurrence-free survival after radical
hormone (LHRH) agonist in 98 patients who underwent radical prostatectomy for locally advanced, lymph-node-negative prostate
prostatectomy and pelvic lymphadenectomy and were found to have cancer with a median follow-up of 6.1 years, although there was no
The overall survival at seven years was significantly difference in terms of overall survival and considerable toxicity was
improved in patients who had early hormonal treatment compared with also observed in the flutamide-receiving arm.
those who had delayed treatment (i.e. starting at the moment of
progression). In metastatic asymptomatic patients, the death rate was In summary, as soon as a micrometastatic disease is suspected to be
32% in cases of immediate hormonal treatment compared with 49% in responsible for relapse, the best therapeutic option is hormonal
cases of delayed treatment. In another study, Moul et al. compared two therapy. The best oncological outcomes are obtained with an early
groups of patients with a biochemical recurrence after radical treatment in case of high-risk factors: Gleason score >7 and PSA
prostatectomy (i.e. PSA >0.2ng/ml).
The first group had early hormonal doubling time <12 months. In this situation, chemotherapy (docetaxel)
treatment (n=355), and the second group underwent the same could also be an alternative option in the near future; trials are
treatment but only when metastasis occurred (n=997). After a mean currently ongoing to answer this question.
follow-up of 5.2 years, patients who benefited from immediate
hormonal treatment had at least one of the following characteristics: Conclusion
biochemical relapse before 12 months after surgery, a pathological A significant proportion of patients who undergo a radical
specimen Gleason score >7, a pT3b stage and a lymph-node invasion. prostatectomy for localised prostate cancer develop PSA recurrence.
In terms of the treatment for such PSA recurrence, some patients may
When an adjuvant hormonal treatment is proposed, another choice is be good candidates for local radiotherapy, whereas others may be
between LHRH agonist and androgen antagonist. According to indicated to undergo hormonal manipulation rather than
Schellhammer et al., there is no decisive advantage in favour of whole radiotherapy. Although the pathological findings and post-operative
Anti-androgen monotherapy with bicalutamide serum PSA parameters may be useful for predicting the pattern of
(150mg) or flutamide (750mg) has been shown to be efficient compared recurrence, it is still quite difficult to identify the most appropriate
with orchiectomy in metastatic patients with a PSA <100ng/ml. In candidates for each type of treatment. In the low- and moderate-risk
addition, intermittent hormonal treatment appears to improve the quality groups, patients should undergo active surveillance, and adjuvant
of life of patients by lowering the PSA and decreasing the cost. Thus, it treatment can be started at the time of biochemical relapse. In the
appears to be a viable alternative to immediate or delayed treatment.
high-risk group, an immediate adjuvant treatment is recommended. n
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