|
PATHOLOGY
Prognostic
factors and reporting of prostate carcinoma in radical prostatectomy and
pelvic lymphadenectomy specimens
Epstein JI, Amin M, Boccon-Gibod L, Egevad L, Humphrey PA, Mikuz G, Newling
D, Nilsson S, Sakr W, Srigley JR, Wheeler TM, Montironi R
Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland,
USA
Scand J Urol Nephrol Suppl. 2005; 216: 34-63
- This
paper, based on the activity of the Morphology-Based Prognostic Factors
Committee of the 2004 World Health Organization-sponsored International
Consultation, describes various methods of handling radical prostatectomy
specimens for both routine clinical use and research purposes. The correlation
between radical prostatectomy findings and postoperative failure is
discussed in detail. This includes issues relating to pelvic lymph node
involvement, detected both at the time of frozen section and in permanent
sections. Issues of seminal vesicle invasion, including its definition,
routes of invasion and relationship to prognosis, are covered in detail.
The definition, terminology and incidence of extra-prostatic extension
are elucidated, along with its prognostic significance relating to location
and extent. Margins of resection are covered in terms of their definition,
the etiology, incidence and sites of positive margins, the use of frozen
sections to assess the margins and the relationship between margin positivity
and prognosis. Issues relating to grade within the radical prostatectomy
specimen are covered in depth, including novel ways of reporting Gleason
grade and the concept of tertiary Gleason patterns. Tumor volume, tumor
location, vascular invasion and perineural invasion are the final variables
discussed relating to the prognosis of radical prostatectomy specimens.
The use of multivariate analysis to predict progression is discussed,
together with proposed modifications to the TNM system. Finally, biomarkers
to predict progression following radical prostatectomy are described,
including DNA ploidy, microvessel density, Ki-67, neuroendocrine differentiation,
p53, p21, p27, Bcl-2, Her-2/neu, E-cadherin, CD44, retinoblastoma proteins,
apoptotic index, androgen receptor status, expression of prostate-specific
antigen and prostatic-specific acid phosphatase and nuclear morphometry.
- Editorial
Comment
This is a long paper of the Consensus meeting held in Stockholm in 2004
and sponsored by the World Health Organization. I will emphasize only
some of the topics of interest for the urologist.
1. Seminal vesicle invasion: this finding in a radical prostatectomy
specimen markedly diminishes the likelihood of cure. In contemporary
series of men with positive seminal vesicles and negative pelvic lymph
nodes, 5-year biochemical progression-free rates range from 5% to 60%.
The diagnosis of invasion should be restricted to invasion of the muscle
layer of the seminal vesicle that is a structure exterior to the prostate.
Cases that some have diagnosed as invasion of the “intraprostatic
portion” of the seminal vesicle should be regarded as invasion
of the ejaculatory duct. Possible routes of seminal vesicle invasion
are: 1) extension into soft tissue adjacent to the seminal vesicle and
then into the muscle layer; 2) invasion via the sheath of the ejaculatory
duct and extending up into the seminal vesicle muscle layer; and 3)
discontinuous metastases. There are conflicting studies as to whether
the first or second method is most common. Metastases are the least
common mode of spread.
2. Extraprostatic extension: because the prostate lacks a discrete capsule,
the term extraprostatic extension should be used instead of “capsular”
penetration to describe tumor that has extended out of the prostate
into periprostatic soft tissue. Prognosis has relation to extraprostatic
extent. This evaluation, however, is controversial. Unfortunately, the
most prognostic method to substratify the degree of extraprostatic extent
remains the subjective designation of focal versus nonfocal.
3. Margins of resection: the pathological definition of positive margins
of resection is “tumor extending to the inked surface of the prostatectomy
specimen which the surgeon has cut across”. There are two causes
for positive margins: transection of intraprostatic tumor (iatrogenic
incision) and non-iatrogenic. Tumors in stage T2 with positive surgical
margins are designated stage T2+. This is because the pathologist cannot
evaluate if the tumor in the area with positive margin is confined to
the gland or has extraprostatic extension. The pathology report should
also indicate the presence of normal prostate tissue at the resection
margin level. This might help the urologist explain why the serum PSA
in patients with such a feature remains detectable after radical prostatectomy.
In fact, the serum PSA value, even though very low, is not linked to
tumor recurrence and persistence, but to incomplete resection of the
prostate gland.
4. Gleason score: is a very powerful predictor of progression following
radical prostatectomy. Gleason scores 2-4 are rarely seen. Most of the
cases were tumors incidentally found on transurethral resection (stages
T1a and T1b). All men with only Gleason scores 2-4 tumor at radical
prostatectomy are cured. The prognosis of Gleason scores 5-6 shows a
spectrum in its biologic behavior depending on other variables such
as margin status and organ-confined status. Gleason score of 7 have
a significantly worse prognosis than those with Gleason score 6. It
is controversial the prognostic significance of Gleason score 3 + 4
versus Gleason score 4 + 3. Gleason scores 8-10 account for only 7%
of the grades seen at radical prostatectomy. Typically, these tumors
are highly aggressive and present at an advanced stage such that are
not amenable to localized therapy.
Dr.
Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil |