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Optimal Duration Of
Androgen Deprivation In Patients With PSA > 20 Ng/Ml Treated With
External Beam Radiotherapy - Take Home Message: Longer Is Better Than
Shorter in High-Risk Disease
(March 2008)
The conclusion: ADT
duration of 12-24 or >24 months significantly improved bNED, cause-specific survival
(CSS), and overall survival (OS) as compared to < 6 and 6-12 months.
This report by a
British Columbia consortium in The Canadian Journal of Urology,
August 2007, followed 307 men divided into four groups equally matched
for age, PSA, and Gleason score. All men were treated with EBRT and an
LHRH agonist: group 1, androgen deprivation for <6 months (n=71); group
2, 6-12 months (n=80); group 3, 12-24 months (n=72); and group 4, >24
months (n=84). In those groups Clinical Stage T2 and T3 was present in
84%, 69%, 68%, and 85%; and a pelvic radiation boost was delivered in
9%, 50%, 44% and 43%; and the median follow-up per group was 63, 31,
32,and 53 months, all respectively for groups 1-4. The total external
beam radiation dose was 66-72 Gy, which is less than currently
considered standard.
Results: "At five years
the rates of bNED were 34%, 35%, 47%, and 77% for groups 1-4,
respectively." At five years the CSS rates were 82%, 82%, 97% and 92%;
and the OS rates were 74%, 77%, 83% and 92%, all respectively.
In the final analysis,
"For bNED outcomes a statistically significant advantage was seen for
durations of ADT of 12-24 months and >24 months as compared to shorter
durations. However, significant improvement in CSS and OS was limited to
patients who received >24 months of ADT."
SHORT-TERM NEOADJUVANT
ADT AND ERBT FOR LOCALLY ADVANCED PROSTATE CANCER
The January JCO
carried the update of the well-known Roach RTOG 8610 trial of 2 months
of combined androgen blockade prior to and concurrent with ERBT for
high-risk cancer - i.e. bulky T2-T4 tumors. In the comparison between
ADT+EBRT v EBRT alone, "There was a statistically significant
improvement in 10-year disease-specific mortality, (23% v 36%; p=.01);
distant metastases, (35% v 47%; p=.12); disease-free survival, (11% v
3%; p=<.0001); and biochemical failure, (65% v 80% p=<.0001) - all
comparisons favoring the addition of ADT to EBRT compared to ERBT alone.
[Editors note: What's
the Gestalt here? In the global picture for men with high-risk disease
the benefit of longer ADT increases as the risk for recurrence
increases; and, some ADT is better than none. The argument against
prolonged ADT derives from the well known toxicities of protracted
androgen deprivation. However, increasing usage of intermittent androgen
deprivation and the utility of less toxic combinations such as
dutasteride/bicalutamide have potential to improve the benefit/toxicity
ratio and permit longer ADT usage.]
   
This nomogram below is
related to the article in the Jan/Feb PC Commentary, "Gleason Score
Upgrading From Biopsy to Prostatectomy Specimen". No nomogram is
perfect, but this presentation suggests the many factors that are
involved and their relative importance. The nomogram was published in
the article "Clinical Predictors of Gleason Score Upgrading:
Implications for Patients Considering Watchful Waiting, Active
Surveillance, or Brachytherapy" by Kulkami et al. in CANCER
June 15, 2007 / Volume 109 / Number 12, Page 2436. Reproduced with
permission of Wiley- Inc.
Figure 2. Nomograms for predicting upgrading of
biopsy-derived low-risk prostate cancer. To use the nomogram, identify
patient values of each variable on its representative axis. Draw a
vertical line for each value to the Points axis to determine how many
points are accumulated for each variable. Identify the sum of the total
Points on the Total Points axis and draw a vertical line to the
Probability of Upgrading axis to determine the patient’s chance of
harboring high-grade disease. Uro-path indicates expert genitourinary
pathologist; Synt: sextant biopsy (+/-nodule/lesion); Ext. extended
10-core biopsy (+/- nodule/lesion).
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