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Long-Term Prognostic Significance of
Primary Gleason Pattern in Patients With Gleason Score 7 Prostate
Cancer: Impact on Prostate Cancer Specific Survival, J Urol, Feb
2006
(November 2007)
This article by Tollefson et al. from the Mayo Clinic
presents the 10 year outcome data based on 1688 men treated with radical
prostatectomy and pelvic lymphadenectomy for Gleason Score 7 prostate
cancer and is an appropriate counterpoint to the brachytherapy article
above. Comparison of the details in the two articles also highlights the
difficulty of comparing data from these two primary treatment modalities
even when the populations under study are defined as carefully as
possible.
The executive summary: With respect to cancer
specific survival (CSS) at 10 years there was no significant difference
between the CSS in the two studies: for BT the 10 year CSS for biopsy
Gleason score (GS) 3 + 4 vs GS 4 + 3 was 96.7% vs 93.3%; and for the
Mayo study the figures were 97% vs 93% for pathologic GS 3 + 4
vs. 4 + 3.
It is possible, however, that because of the larger
number of men in this Mayo Clinic study (1688 vs 530 ) the CSS outcome
difference between the two Gleason Scores under study in the Mayo trial
reached statistical significance, p=0.013. It's tricky to try to factor
into these comparisons the 25% or more upgrading that is known to result
in the transition from biopsy GS to pathologic GS, but conceivably
moving some of the postulated "undergraded" primary GS 4 cancer in the
Merrick brachytherapy study from the GS 3 + 4 column into the 4 + 3
group might have increased the spread between the two categories in the
BT study.
What were the differences between the details of the
Merrick and Mayo trials? No men in the Mayo study received ADT either
neoadjuvantly or in the immediate postoperative period. PSA failure
threshold was O.4 ng/ml in both studies, but the Mayo article does not
specify how many men ultimately received XRT or ADT leading into their
calculation of CSS. However, in the BT study only 10% of men received
post treatment ADT for longer than 6 months
The ultimate arbiter of Gleason score is the histology in
the surgical specimen. In the Mayo study pathologic examination of the
surgical specimen diagnosed seminal vesicle involvement in 15.2% of the
GS 3 + 4 group vs 22.7% in the GS 4 + 3 cohort; and positive surgical
margins were found in 34% vs 40%, respectively. There was no mention as
to the frequency of extracapsular extension. These pathologic features
could be expected to be about the same in the Merrick study. And since
77% of patients in the BT study received adjuvant XRT, these adverse
pathologic features would have been unknowingly treated initially. The
Mayo study excluded men found at surgery to have lymph node involvement.
The ultimate rate of 10 year estimated progression free
survival in the BT study was 97.0% vs 92.9% (primary GS 3 vs 4).
Progression-free survival from initial surgery in the Mayo study was 48%
vs 38% (GS 3 vs 4), which rose to a CSS outcome of 97% vs 93% with the
aid of adjuvant XRT. The difference in PFS between the two studies
clearly indiicates the beneficial effect of early adjuvant XRT treatment
in the BT series, whereas the ultimate similarity in CSS data between
the studies indicates that subsequent adjuvant XRT therapy effectively
"salvaged" many men with early biochemical progression in the Mayo
study.
Because of the inherent
nature of the two modalities, there is no way to resolve the these
difficulties which prevent a perfect comparison between the two. Each of
the two modalities of primary therapy has its inherent strong points.
The Merrick study would suggest that their technique of radiation
delivery overrides any adverse influence on CSS resulting from the more
aggressive primary Gleason pattern 4, whereas the Mayo analysis
concludes that their study continues to support "pathological Gleason
pattern 4 as an independent predictor of survival in patients with GS 7
prostate cancer. Overall, however, both studies show that when BT and RP
are carried out by skilled practitioners, the cancer specific survival
for men with GS 7 cancer can be encouragingly favorable.
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