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Percentage of Positive Biopsy Cores: Riddle - “When is the risk of a
Gleason 4 + 3, not that of a “4 + 3”? Answer: When less than 50% of the
cores show cancer. (April 2006)
The riddle’s answer is
discussed in “Impact of the percentage of positive biopsy cores on the
further stratification of primary grade 3 and grade 4 Gleason score 7
tumors in radical prostatectomy specimens” by Vira et al., UROLOGY
66(5),2005.
This study examined the
median biochemical progression-free survival (bPFS), set at less than 0.2
ng/mL, at 5 years for 290 men with primary biopsy grade 3 tumors and 89
men with primary grade 4. Consistent with the bulk of prior analyses, the
60-month probability of bPFS for men with primary grade 3 tumors was 71%
versus 55% for grade 4. However, the new finding from this study was that
“When segregated for percentage of core biopsies positive ... the 60-month
actuarial PSA progression-free survival for patients with [primary] grade
3 and 4 and less than 50% core biopsies positive as compared with
grade 3 and 4 and 50% or more positive biopsies [was] 85%,
85%, 61% and 33%, respectively. In multivariate analysis of this
intermediate-risk population (after taking into account the predictive
factors of PSA level, surgical margin status, and pathologic stage) the
primary Gleason grade lost independent significance. However, on subgroup
analysis of those men with > 50% positive cores, the dominant Gleason
grade remained a significant independent predictor of biochemical
progression. The take-home message of this study: “Patients with primary
grade 4 disease who have 50% or fewer biopsies positive have an excellent
prognosis after radical prostatectomy”.
But in any sampling
system such as core biopsies there is always a whiff of ambiguity. Partin,
Walsh, Epstein et al. analyzed the “Relationship between primary Gleason
pattern on needle biopsy and clinicopathologic outcomes among men with
Gleason 7 adenocarcinoma of the prostate”, UROL. 67, Jan 2006. Relevant to
the Vira article (above) they determined by examining surgical the
specimens of 320 men with Gleason 7 tumors on core biopsy that
approximately 47% of men with a Gleason pattern of 4 + 3 on needle biopsy
were downgraded on final pathologic analysis to primary pattern 3 or less,
and those with biopsy Gleason score of 3 + 4 were upgraded in 24% to
primary pattern 4 or more. The PSA recurrence-free outcomes were
consistent with what was expected from the scores on the surgical
specimens.
The literature is replete
with many studies documenting that the percentage of positive biopsy cores
(PPBC) is an independent predictor of pathological stage and clinical
outcome, taking its place along with the basic standards of PSA, Gleason
score and clinical stage. And a predominant finding in these studies has
been that within each of the standard risk categories, prediction can be
further refined by considering this PPBC variable, reinforcing the
intuitive generalization that “fewer is better”.
The increment of improved
prediction added by PPBC is not uniform among the three standard risk
categories. One clinically useful observation is discussed in the classic
paper by D’Amico et al., “Clinical Utility of the Percentage of Positive
Prostate Biopsies in Defining Biochemical Outcome After Radical
Prostatectomy for Patients with Clinically Localized Prostate Cancer”, JCO,
Mar 2000. This study of 960 men matched the well known bPFS outcome graphs
based on Partin’s three standard risk categories with graphs displaying
outcome data within each risk group further
segregated by PPBC data. Their PPBC groupings were <34%, 34% - 50%, and >
50%. Result: It was in the intermediate-risk group, PSA >10 but
< 20 ng/mL, or Gleason score 7, or clinical stage T2b (‘92),
where the PPBC was most revealing. The < 34% PPBC cohort showed a ~90% 5
year bPFS, whereas the standard Partin data assigns the intermediate-risk
group, unstratified by PPBC, a bPFS figure of ~ 50%. In the high-risk
group an important further stratification was also seen: 4 year bPFS for
the <34% group, 70%, versus the Partin estimate, unstratified for PPBC, of
30%. In the low-risk group further stratification by PPBC was not further
informative. A potential weakness of the study was that a sextant biopsy
strategy was most commonly used. D’Amico concluded, “the stratification of
PSA outcome after RP provided by percentage of positive biopsies was also
clinically significant in that the vast majority (78% to 80%) of the
intermediate-risk patients in the study and in the validation cohorts
could be categorized into a high- or low-risk category for PSA outcome
after RP”. In D’Amico’s opinion this study finding was clinically useful,
since it is “the intermediate-risk group, for whom improvements in the
prediction of PSA outcome are most needed.” Again, fewer is better, and
the D’Amico study is complimentary to the Vira study already discussed.
The risk of seminal
vesicle involvement (SVI) is also independently predicted by considering
PPBC. SVI increases with increases of positive biopsy cores. Antunes et
al. (BJU Int. 96, 2005) in their analysis of 534 patients with clinically
localized prostate cancer confirmed that the standard three predictors
were significantly associated with PPBC, but PPBC was the only independent
predictor of seminal vesicle cancer. In a study of the surgical specimens
of 1056 men, of whom 7.4% had SVI, only 0.5% of men with < 17% of core
biopsies positive had involvement (Guzzo TJ, J. Urol. Feb 2006). In their
article, ”A nomogram to predict seminal vesicle invasion by the extent and
location of cancer in systematic biopsy results” (J.Urol. 2003 Oct),
Scardino, Wheeler, Kattan et al. pointed up the increased risk of SVI
arising from positive cores at the base of the prostate. Their
finding: “Cancer was present in a biopsy core from the base in 437
patients, of whom 12.8% had SVI compared with only 1.2% of the 326 without
cancer at the base”. Their conclusion: “The predictive accuracy of a
standard model that included only stage, grade and PSA was maximally
enhanced by including the percent cancer at the base (p=0,0013)”.
Bottom Line:
The percentage of biopsy cores positive is a powerful independent
predictor of pathologic stage and outcome.
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