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Konsep Prostat Kanser PDF
Konsep Prostat Kanser PDF
REVIEW
Prevention is an important strategy for limiting prostate cancer morbidity and mortality. Two major
types of prevention are primary (reduction of incident cases) and tertiary (inhibition of disease
progression and recurrence). Pharmacological and dietary interventions have potential functions in
both the primary and tertiary prevention of prostate cancer. Five-a reductase inhibitors (5-ARIs)
reduce the incidence of prostate cancer in both general and higher-risk populations and are
currently under study for tertiary prevention in active surveillance and biochemical recurrence
patients. Selenium, vitamin E, and vitamin C do not prevent incident prostate cancer in the general
population; however, other promising diet-based interventions are currently under study for
tertiary prevention. We recommend consideration of 5-ARIs for prostate cancer prevention in
(1) asymptomatic men with a PSA p3.0 ng ml–1 who are undergoing or anticipate undergoing
PSA screening for early detection of prostate cancer and (2) asymptomatic men with PSA X2.5 and
p10 ng ml–1 and an earlier prostate biopsy negative for cancer. Men should be informed of the
potential risks of 5-ARI therapy. Currently, there is neither clinical evidence to support the use of
5-ARIs for tertiary prevention in active surveillance or biochemical recurrence populations, nor
micronutrients for prostate cancer prevention of any type.
Prostate Cancer and Prostatic Diseases (2010) 13, 300–306; doi:10.1038/pcan.2010.18; published online 22 June 2010
Five hundred and fourteen patients with biopsy- progression events in expectant management finished 303
proven HGPIN were randomized to 20, 40, or 60 mg accrual in 2007 and is expected to complete follow-up in
toremifene, or placebo. Prostate biopsies were repeated 2010.46
at 6 months and 1 year. Although toremifene cohorts Similarly, the avodart after radical therapy for prostate
showed potential efficacy at all three dosages, only those cancer study is a 2-year RCT to test the hypothesis that
in the 20 mg arm had a statistically significant decreased dutasteride will reduce disease progression in patients
risk of cancer on repeat biopsy compared with placebo with biochemical recurrence after primary treatment for
(24.4% versus 31.2%, Po0.05). There was no increased prostate cancer. Biochemical (PSA-only) recurrence after
risk of serious adverse events or thromboembolic events radical prostatectomy or radiotherapy for localized
in the toremifene cohorts. The authors estimated that prostate cancer occurs in 27–53% of patients within
toremifene would prevent 6.8 cancers annually per 100 10 years.47 Biochemical recurrence predates clinically
men treated with toremifene. Although it is unclear why detectable metastatic disease by an average of 8 years.48
only the 20 mg arm showed a significant reduction in the In 1995, Andriole et al.49 reported that men with
risk of prostate cancer, the authors hypothesize that it detectable PSA after radical prostatectomy treated with
was the greater selectivity and inhibition of the a subtype finasteride experienced delay in the rise of serum PSA
of the estrogen receptor, which stimulates prostate and reduction in local and distant recurrences compared
growth. Still, given current clinical recommendations with a placebo cohort. It is hypothesized that dutasteride
for HGPIN, toremifene should not be considered for may be used for tertiary prevention of progression from
prostate cancer prevention at this time.42,44 PSA-detectable disease only after primary treatment to
clinically detectable metastatic disease and thus prevent
or delay the need for second-line treatment.50
Avodart after radical therapy for prostate cancer study
Tertiary prevention is an ongoing European trial in which patients were
Tertiary prevention focuses on halting disease progres- initially treated for prostate cancer with intent to cure
sion and recurrence in patients with prostate cancer. and subsequently experienced biochemical recurrence.
The widespread use of PSA screening has led to a stage Participants are stratified by earlier therapy and rando-
migration in prostate cancer, with men being diagnosed mized to dutasteride daily or placebo. Patients who
with low-pathologic and low-clinical stage disease underwent earlier radical prostatectomy must experience
compared with historical cohorts.45 As a result, many three PSA rises from nadir, with each being X4 weeks
tumors that were not earlier detected are now being apart, and a PSA between 0.4 and 10 ng ml–1 at
diagnosed at early stages and are potentially amenable to enrollment. Patients who underwent earlier radiation
tertiary prevention. In addition, treatment with intent to therapy must wait at least 1 year from end of radio-
cure at younger ages allows for a longer window of time therapy and then must have three increases in PSA from
for potential disease recurrence or progression during nadir, with each rise X4 weeks apart and an enrollment
a patient’s lifetime. PSA of 2–20 ng ml–1. Exclusion criteria include men with
For these reasons, hormonal and dietary prevention rapid (o3 months) or prolonged (424 months) PSA
strategies are currently under study in prostate cancer doubling time. It is estimated that 276 patients will
patients. Importantly, studies of tertiary prevention are enroll. Study end points include time to PSA doubling,
all ongoing: to date, there are no results from large RCTs on time to disease progression, treatment response (PSA
which to base clinical recommendations. decrease or increase of 15% from baseline), changes in
PSA and PSA doubling time, and changes in anxiety.
PSA will be measured every 3 months and patients with
Reduction by Dutasteride of Clinical Progression Events evidence or signs of disease progression will be offered
alternative treatment strategies. The results from this
in Expectant Management, Therapeutic Assessment of
study are likely to be unavailable for several years.
Rising PSAs, Avodart after Radical Therapy for Prostate The therapeutic assessment of rising PSAs study is an
Cancer and Men’s Eating And Living studies ongoing RCT designed to determine the impact of
Reduction by dutasteride of clinical progression events dutasteride on patients with castrate-resistant prostate
in expectant management is an ongoing trial testing the cancer on bicalutamide.51 The rationale behind this
hypothesis that the 5-ARI dutasteride will prevent study is that low levels of circulating testosterone may
disease progression in patients with low-risk prostate still be converted to DHT by 5-a reductase, and this DHT
cancer on active surveillance. Three hundred men aged has a greater affinity for the androgen receptor than
50–80 years with biopsy-proven clinical T1c or T2a bicalutamide. Thus, more complete blockage of the
prostate cancer diagnosed within the earlier 6 months androgen receptor will theoretically be achieved if it is
were randomized to receive dutasteride 0.5 mg per day blocked directly with bicalutamide and concurrently
or placebo for 3 years. At baseline, participants had intraprostatic DHT levels are suppressed with dutaste-
Gleason sum p6 disease and a serum PSA p10 ng ml–1. ride. Approximately 150 subjects with PSA progression
Repeat biopsies will be performed at 1.5 and 3 years, and despite androgen deprivation therapy, with PSA bet-
PSA results will be provided to physicians and partici- ween 2 and 20 ng ml–1 and serum testosterone o50 ng
pants. The primary study end point is time to disease per 100 ml, and who have a negative bone scan within
progression (defined as time to treatment or pathologic 8 weeks of enrollment and anticipated 42-year survival,
progression). Of note, these investigators hypothesize are randomized to bicalutamide 50 mg once daily and
that dutasteride may reduce anxiety of patients on active either dutasteride 3.5 mg daily or placebo.
surveillance by decreasing PSA and potentially dampen- Finally, the men’s eating and living study is a multi-
ing PSA spikes. Reduction by dutasteride of clinical center, 5-year, National Cancer Institute-funded RCT
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