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The
Utility of Bone Scans in Recurrent Prostate Cancer (June 2005)
A bone scan showing malignancy is a rarity when performed
in association with the initial work-up for prostate cancer if the PSA
value is less than 20 ng/mL. And this 1% likelihood is almost always
related to high-risk disease with a PSA value approaching 20 ng/mL., as
discussed in detail in PCa Commentary and indexed under “Diagnostics”. The
focus of this article, however, is the utility of bone scanning at the
point of disease recurrence after failure of primary therapy, a subject
infrequently addressed in the literature, but the topic of “Radionuclide
bone scintigraphy in patients with biochemical recurrence after radical
prostatectomy: when is it indicated”, by Pablo Gomez, Mark Soloway, et al,
BJU Int. Vol.94, 2004.
This study analyzed the characteristic of 35 men with
biochemical recurrence - PSA >0.4 ng/mL - who were scanned within 3
months of recurrence and categorized with respect to having a negative
(group 1) or positive (group 2) bone scan. The mean follow-up was 70.4
months. “In group 1 the mean PSA at the bone scan was 5.2 ng/mL and 76% of
patients had a PSA of <7 ng/mL. In group 2 the mean PSA at the bone scan
was 30.7 ng/mL and all patients had a PSA of >7 ng/mL. The only
significant difference between the groups was the PSA at the time of the
bone scan (P<0.001).” However, the PSA velocity was informative: “Nine of
ten patients in group 2 had a PSA velocity of >0.5 ng/mL/month and
64% in group 1 has a PSA velocity of <0.5 ng.mL/month”.
The authors cite Cher et al (J Urol 1998; 160; 1387-91) who
noted a less than 1% likelihood of bone scan positivity at the time of
recurrence if the PSA were <10 ng/mL and concluded that in patients who
progress after RP “bone scanning is of limited use until the PSA increases
to >30-40 ng/mL”. Also cited was Kane et al (Urology 2003; 61: 607-11). In
their study of men with recurrence the mean value for a positive scan was
61.3 ng/mL, PSA velocity 22.1 ng/mL/month. For a negative scan the mean
PSA value was 4.9 ng/mL and PSA velocity was 0.5 ng/mL/month. Only three
of 67 (4.5%) scans were positive at a PSA level of < 10 ng/mL.
The Gomez report concluded that in men without
skeletal symptoms who exhibit PSA recurrence after RP a positive bone scan
is unlikely if the PSA is <7 ng/mL “whereas it is likely to be [positive]
if the PSA level is >20 ng/mL.”
While this Commentary article was in gestation, a “must
read” analysis appeared in the March 20 issue of the JCO, ”Pattern of
Prostate-Specific Antigen (PSA) Failure Dictates the Probability of a
Positive Bone Scan in Patients With an Increasing PSA After Radical
Prostatectomy”, by Dotan, Kattan et al. A reading of this report is an
excellent exercise for setting the mental compass for this subject,
summarizing as it does the relevant prior studies and providing
informative biologic insights. Once again the cardinal value of the PSA
velocity emerges as the best reflection of a prostate cancer’s underlying
pathobiology as it does at almost any point in the life history of the
disease.
The data base for the study consists of 239 men, having had
no androgen suppression, whose post RP PSA rose above 0.04 ng/mL. They had
been scanned at the discretion of their physicians. The study indicated
that most of the scans ordered in this general clinical practice were
negative. Only 14.5% were positive. The purpose of this study’s analysis
was to incorporate predictors into a nomogram (to be available at http://www.nomogram.org)
to assist in selecting the most appropriate candidates for bone scanning.
Of the eight predictors built into the nomogram the two most influential
for predicting a positive scan were the PSA velocity, P = 0.003, and the
PSA value (the “trigger PSA”), preceding the scan, P <0.001. The median
and mean for the trigger PSA in all patients were 3.1 and 13.4 ng/mL, and
in the group of men with PSA values of 0 to 10 and 10.1 to 20 ng/mL the
bone scans were positive in 4% (median 8.4 ng/mL) and 36% (median 13.2 ng/mL),
respectively.
The PSA velocity, rate of rise expressed as ngs/mL/month,
was based on the last three tests prior to the scan, with each separated
by more than 30 days. Both the PSA velocity and the PSA slope can be
conveniently calculated by using Kattan’s Web site nomogram. The median
PSA velocity for positive scans was 1.4 ng/mL/month vs 0.12 for negative
scans. Interestingly the PSA doubling time was insignificant as a
predictor, P = .83. For positive scans the doubling time was 5.2 months vs
6.6 months for negatives. The nomogram was “constructed with an overfit-corrected
concordance of .93”, confirming its reliability.
Bottom Line: Evidenced based
data is available to provide guidance for the optimal use of bone scanning
in men with a rising PSA after primary treatment.
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