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Nadir PSA after Radiation Therapy and Androgen Deprivation for Metastatic
Disease (February 2007)
Not surprisingly, the
lowest PSA nadirs after radiation therapy and androgen suppression are
associated with the longest freedom from biochemical recurrence and
prostate cancer-specific survival. Here's the data.
1. EBRT for T1 - T2
Cancer: The outcome of radiation therapy (76 Gy) in 1000 men was
reported by Pino et al. from Fox Chase Cancer Center, "Prostate-Specific
Antigen Nadir Within 12 Months of Prostate Cancer Radiotherapy Predict
Metastases and Death", CANCER Jan 1, 2007. The analysis reported
the outcome for men who achieved a PSA of <2 ng/mL during the 12 months
after treatment versus those who did not.
This discriminant was
chosen as opposed to the actual PSA nadir, which often is delayed to a
median of 3 years - "even as long as 8-10 years" after EXRT; and in this
study the median nadir was reached at a median of 35.2 months. "The 1-year
time point [nPSA12] was investigated because we reported previously that
the overwhelming majority of the drop in PSA after RT is during the first
year." In this 1000 man study the median PSA during the first
post-treatment year was 1.2 ng/mL. Median study follow-up was 58 months.
"Dichotomized nPSA12 (<2 versus > 2 ng/mL) was independently
related to distant metastases (DM) and cancer-specific mortality (CSM)."
Results: biochemical failure at 5- and 10-years for nPSA12 <2
ng/mL was 26% and 30%versus 36% and 46% for nPSA12 >2 (p=0.0015);
distant metastases at 5 and 10 years for nPSA12 <2 ng/mL was 2%
and 4% versus 8% and 19% for >2 (p=<0.0001). Overall survival
projected to 10 years was not significantly different: 26% (<2) vs
35% (>2). The hazard rate for cause-specific mortality was 3.9 for those
men with a nPSA12 of >2 ng/mL. Conclusion: nPSA12 was recommended as a
strong predictor of outcome after RT and would serve to identify patients
at high risk for progression.
2. Androgen
Deprivation In Metastatic (D2) Disease: PSA nadir after 7 months of
ADT in metastatic prostate cancer is the best factor for predicting
overall survival.
It has been canonical
that in D2 disease that the duration of response for ADT clusters around
18 to 24 months. Abstract 4517 (reporting SWOG Trial 9346), ASCO
2006 provides OS data usefully categorized into cohorts based on the PSA
achieved after 7 months of Zoladex/Casodex therapy, and allows a finer
focus on predicting outcome from ADT. The range in OS was surprisingly
broad, 13 to 75 months. The study was based on 1134 men (85%) of the
study-eligible 1345 men, median age 70 years, baseline PSA > 5 ng/mL,
whose PSA became <4 ng/mL during the study period. Results: Median
OS was 75 months for the 45% of men achieving a PSA of <0.2 ng/ml
after 7 months of ADT induction; 44 months for the 33% whose PSA fell
between 0.2 and 4.0 ng/mL; and 13 months for those whose PSA was > 4 ng/mL
at the end of the induction period. "Survival was defined as time to death
after 7 months of ADT." A poor response to ADT was associated with
co-morbidity (performance status of 2 or 3), bone pain at initiation of
ADT, and Gleason score > 8.
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