european urology 53 (2008) 448–452
available at www.sciencedirect.com
journal homepage: www.europeanurology.com
Words of Wisdom
Re: Identification of Patients with Prostate Cancer
Who Benefit from Immediate Postoperative Radio-
therapy: EORTC 22911
Van der Kwast TH, Bolla M, Van Poppel H, Van Cangh
P, Vekermans K, Da Pozzo L, Bosset JF, Kurth KH,
Schröder FH, Colette L
J Clin Oncol 2007;25:4178–86.
Expert’s summary:
In 1992, the European Organization for Research and
Treatment of Cancer (EORTC) initiated a multicentre,
randomised trial on immediate adjuvant radiother-
apy versus wait-and-see after radical prostatectomy
on 1005 patients at high risk of recurrence (N0M0,
pT3a or b, or positive surgical margins pT2). The 5-yr
biochemical and loco regional progression-free sur-
vival rates were significantly better for the group
receiving immediate radiotherapy (74% vs. 52.6%
and 95.4% vs. 85.5%, respectively). The benefit was
substantial in all subgroups of risk factors [1]. One
experienced uropathologist reviewed 552 of the spec-
imens and correlated surgical margins, extracapsular
extension, seminal vesicle invasion, and Gleason
score with the 5-yr biochemical-free survival. The
presence of positive surgical margins (322 patients)
was the only predictive factor of positive effect of
radiotherapy to such an extent that there was
no benefit in case of negative margins. For every
1000 patients at high risk of recurrence, adjuvant
irradiation would prevent biochemical relapse at
5 yr for 291 patients in case of positive margins
and only for 88 patients in case of negative margins.
The site of the margins had no influence on the
results.
Expert’s comment:
This critical study stresses four main points.
0302-2838/$ – see back matter
The quality of surgery in high-risk prostate cancer
patients (ie, negative surgical margins) is a signifi-
cant risk factor for biochemical progression-free
survival. The vast majority of scientific publications
on radical prostatectomy reports on functional
results. However, young urologists should still have
in mind the rules of carcinoma surgery for high-risk
patients.
This study will certainly clarify the indications for
adjuvant radiotherapy. However, despite the fact
that immediate radiotherapy increases biochemical
progression-free survival, it also significantly
increases the rate of severe toxic effects (4.2% vs.
2.6%), but its superiority over early salvage irradia-
tion is still debated [1].
Despite the statistical evidence, the clinical benefit
of a biochemical-free survival needs to be established
for men with prostate cancer. This illustrates the
great heterogeneity in study designs and particularly
in the choice of the primary end points, which are not
always pertinent to clinical benefit.
The most troubling result is that surgical margins
were identified as the only significant prognostic
factor only after central pathologic review [2]. The
concordances for surgical margin status, as well
as for extraprostatic extension, between initial
pathology and review were only 69.4% and 57.4%,
respectively [3]. No clear explanation can be found
for this discrepancy considering that the reviewed
cases were recruited from high-volume centres
(supposed to provide experienced pathologic anal-
ysis) and that the definition of surgical margins is
now supposed to be based on a consensus. A close
collaboration between urologists and pathologists is
clearly mandatory in the interpretation of prosta-
tectomy specimens. Also mandatory for every
multicentre trial on prostate cancer is now a
centralised pathology review.
 european urology 53 (2008) 448–452
References
[1] Bolla M, et al. Lancet 2005;366:572–8.
[2] Colette L, et al. Eur J Cancer 2005;41:2662–72.
[3] Van der Kwast T, et al. Virchows Arch 2006;449:428–34.
Re: Radial Distance of Extraprostatic Extension
Measured by Ocular Micrometer is an Independent
Predictor of Prostate-Specific Antigen Recurrence.
A New Proposal for the Substaging of pT3a
Prostate Cancer
Sung MT, Lin H, Koch MO, Davidson DD, Cheng L
Am J Surg Pathol 2007;31:311–8.
Expert’s summary:
Extraprostatic extension (EPE; ie, pT3a in the current
2002 TNM staging system) is an unfavorable prog-
nostic factor for prostate cancer. This group, led by
Professor Liang Cheng (Indiana University, Indiana-
polis, IN, USA), analyzed the extent of EPE by eight
quantitative methods to determine which is best for
substaging pT3a tumors. In the univariate analysis,
the radial distance of extraprostatic tumor mea-
sured by ocular micrometer was associated with
prostate-specific antigen (PSA) recurrence. No sig-
nificant association was observed between PSA
recurrence and other measurements of EPE, includ-
ing focal versus established EPE using Epstein’s cri-
terion, focal versus established EPE using Wheeler’s
modified criterion, the number of extraprostatic
neoplastic glands, unilateral versus bilateral invol-
vement, circumferential length of extraprostatic
tumor, unifocal versus multifocal involvement,
and volume of extraprostatic tumor. In the multi-
variate analysis, radial distance remained an inde-
pendent predictor of PSA recurrence. Two- and 4-yr
PSA recurrence-free survival rates were 62% and
35%, respectively, for patients with radial distance
<0.75 mm, as compared with 35% and 18%, respec-
tively, for those with radial distance >0.75 mm.
The radial distance of extraprostatic tumor is
defined as the distance that the tumor protrudes
perpendicularly beyond the outer margin of the
prostatic stroma, as previously described (Fig. 1).
The measurement is made with an ocular microm-
eter. Measurement of radial distance in specimens
containing multiple foci of EPE is recorded for the
focus of maximum extension.
Expert’s comments:
Cancer extending beyond the prostate gland, that is,
EPE, has long been recognized as a poor prognostic
factor both for cancer progression and patient sur-
vival. In a large series of radical prostatectomy speci-
449
Pierre Mongiat-Artus
Saint-Louis Hospital and University Paris VII, France
DOI: 10.1016/j.eururo.2007.11.002
mens reported by Epstein et al [1], EPE was an
important variable to predict cancer progression
by a multivariate analysis, especially for prostate
cancer with Gleason scores of 5–7. Nevertheless,
the clinical outcome of patients with EPE is variable.
In the patients followed by Ohori et al [2], >50% of
those with EPE had no tumor progression at 10 yr.
For this reason, subsequent studies have tried to
subcategorize patients with EPE to separate those
with unfavorable prognosis who may benefit from
additional adjuvant therapy.
In the original 1992 TNM system, EPE was
subcategorized into T3a and T3b on the basis of
the unilateral or bilateral involvement. However, no
significant difference in outcome between these two
groups was identified. Recent TNM staging systems
have abandoned these two subcategories and
assigned T3a for EPE since the 1997 version.
Several quantitative methods have been pro-
posed to substage pT3a tumors: (1) focal versus
established EPE by Epstein’s criterion; (2) focal
versus established EPE by Wheeler’s modified
criterion; (3) number of neoplastic glands in extra-
prostatic tumor; (4) unilateral versus bilateral
involvement; (5) circumferential length of extrapro-
static tumor; (6) total volume of extraprostatic
tumor; (7) unifocal versus multifocal involvement;
and (8) radial distance of extraprostatic tumor.
Professor Cheng’s group found that the radial
distance of extraprostatic tumor was associated
with PSA recurrence both in the univariate and
multivariate analyses.
Fig. 1 – Illustration for measuring radial distance of
extraprostatic extension.