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For the two dysgerminornas in the study by Marx
et al. in which overexpression of p53 was detected by
LIO-7 and DO-1 in greater than 50% of the tumor cell
nuclei, we suggest a further molecular analysis to verify the presence of p.53 mut at’ion.
Liu F-S, Ho ES-C, Chen J-T, Shih RT-P, Yang C-H, Shih A.
Ovvrexpression or mutation of the p53 tumor suppressor
gene does not occur in malignant ovarian germ cell tumors.
Cu:a,icer19Y5;7ti:ZYI -5.
2. Diet1 J, Horny H-P, Kaiserling I:. 1:tcquent overexpression of
p 3 in dysgerminoma of the ovary. Gyriecol Obstet Invest
1994;37: 141-2.
Terada T, Shimizu K, Izumi R, Nakanuma Y. Mcthods i n
pathology. p53 expression in formalin-fixed, paraffin-embedded archival specimens of intrahepatic cholangiocarcinoma: retrieval o f p53 antigenicity by microwave oven heating of tissue sections. M o d I’afkol 1994;7249-52.
Inoue M, Fujita M, Enonioto T, Morimoto H, Monden 7,
Shimano T. Immunohistochemical analysis of p53 in gynecologic tumors. Am I Qin Putkol 1994; 102:665-70.
Rartkova I, Bartek J, Lukas J, Vojtesek B, Staskova Z, llejthar
A , et al. pS3 protein alterations in human testicular cancer
including pre-invasive intratubular germ-cell neoplasia. Int
J Cancer 1991;49:19(i-~202.
Hejmdal K, Lothe KA, 1.ystad S, Holm R, Fossa SD, Borresen AL.
No germline TP53 mutations detected in familial and bilateral
testicular cancer. Genes Ckrornosorn Cancer 199:1;6:92-7.
Fu-Shing Liu, M.D.
Department of Obstetrics
and Gynecology
Tnichung Veterans General Hospital
Taichung, Taiwan
Republic of China
Survival after Radical Retropubic
Prostatectomy of Men with
Clinically Localized High Grade
Carcinoma of the Prostate
went surgery with the intent of having a radical prostatectomy performed. Other authors have found that
when patients with high grade disease undergo exploration, as many as 12% will have grossly positive pelvic
lymph nodes, at which point most urologic oncologists
will abort the procedure.2 I f the authors had chosen
this population of patients, a significantly lower disease specific survival would probably have been encountered among patients with high grade disease
who underwent surgery with the intent of having a
radical prostatectomy performed. Throughout the article, the authors also reler to a 38% likelihood of an
undetectable prostate specific antigen (PSA) at 5 years
among patients with high grade disease (Gleason I 8). However, Figure 1 appears to reflect a rate of about
22%. Thc cumulative effect of the bias of excluding
patients with grossly positive lymph nodes and the
confusion regarding the likelihood of a negative PSA
is to paint a picture of efficacy for radical prostatectomy for the patient who is contemplating the various
treatment options. A more pessimistic view might be
that the patient with high grade disease has at least a
12% (and as high as a 40%1)~risk of positive lymph
nodes and a less than 20% chance of being disease
free (by virtue of a n undetectable PSA) at only 5 years
after treatment with radical prostatectomy. This sober
prognosis suggests that monotherapy with surgery is
probably insufficient and that other modalities (e.g.,
neoadjuvant or continuous hormonal therapy) may
provide a benefit to these patients.
Oefelein MG, Grayhack JT. McVary KT. Survival after radical
retropubic prostatectomy of men with clinically localized high
grade carcirioiiia of the prostate. Cancer 1995;762535-42.
2. Partin AW, Lee BR, (:armichael M, Walsh PC, Epstein JI.
Radical prostatectomy for high grade disease: a reevaluation
1994. J Urol 1994; 151:1583-6.
Tan M. Thompson, M.D.
Medical Corps
Utii t d States, Army
Department o r Suigety
Brooke Army Medical Center
San Antonio, Texas
efelein et al. are to be commended for their indepth review of 238 men (74 of whom had a Gleason scorc 2 7 ) who underwent radical prostatectomy
and were observed for a median of 5.1 years.’ The
conclusion reached was that long term disease specific
Survivid is possible in men with high grade prostate
cancer who undergo radical prostatectomy. Unforlunately, two aspects of their article require comment.
The authors, unlike a previous series,’ began their accounting of the efficacy of surgery with patients who
underwent radical prostatectomy. A more valid denominator is the total number of patients who under-
Author Reply
r. Thompson has expressed his concern regarding 2
aspects of our retrospective reL-iew of patients with
high grade [Gleason grade 4-51, high score [Gl 2 71 adenocarcinoma of the prostate. He questions: 1) the text
citation of a 38% 5-year likelihood of undetectable pros-
CANCER July 1, 1996 / Volume 78 / Number 1
tate specific antigen (PSA) in patients with pathologicdy
organ confined, Gleason grade 2 8 disease, and 2) the
exclusion of individuals in whom the planned radical
prostatectomy was aborted because of the recognition of
metastatic tumor in the lymph nodes.
With regard to the first question, as outlined in the
article, the 5-year likelihood of an undetectable serum
PSA for patients with pathologically staged, organ-confined (Stage T2cNoMo or less) disease with a Gleason
score greater than or equal to 8 was 38% (Table 3) and
was 24% for men with clinically staged localized disease
(Figure 1).Therefore, there is no controversy in the interpretation of these data because our figure represents
pathologic versus clinical staging.
In answering the second question, it is appropriate
to mention our goals in performing this review, i.e., to
provide evidence regarding the possibility/probabilityof
long term, tumor free survival in patients with high grade,
high score tumor who underwent radical prostatectomy.
Published reports indicate men with high grade cancer
are at significant risk for progressive disease and cancer
specific death.’ We focused our data collection on patients identified for risk of carcinoma before the use of
PSA for this purpose was common, hoping to eliminate
consideration of lead-time prejudice in our results. Additionally, the staging information available from biopsy
and blood marker status in our patients was less informative than that currently avadable.Because of these considerations and because we were assessing the results of
radical prostatectomy rather than surgical intervention,
we concentrated on the group of patients who actually
had a radical prostatectomy. We included in our analysis
the nine men who underwent this procedure with unrecognized evidence of metastatic disease until permanent
histologic assessment was performed. Thirty-eightof 289
men in whom the intent to perform radical prostatectomy
was aborted because of recognition of lymph node metastasis were excluded. Six of the 12 men in this excluded
group who had a Gleason score 2 7 on needle biopsy
were alive when our outcomes were reported. Parenthetically, the study of Partin et al.? referenced by Dr. Thompson, excluded men with positive lymph nodes from survival analysis and substratified those with microscopically
positive lymph nodes found on permanent section. Additionally, that study utilized the biopsy rather than the
prostatectomy specimen estimate of Gleason score to report outcomes. The actual Gleason score of the prostatectomy specimen was consequently overestimated in nearly
20% of the patients, possibly introducing favorable bias
outcome. We have reported a 5-year likelihood of undetectable serum PSA of 24% in men with clinically localized
disease (Figure 1) and of 38% for pathology with organ
confined Gleason score 2 8 (Table 3). We emphasize the
pathologically organ confined disease result because this
may represent the maximum attainable surgical cancer
free suMval in this group of patients.
We agree with Dr. Thompson that individuals with
high grade and/or high score carcinoma of the prostate
who undergo radical prostatectomy warrant serious consideration for adjuvant therapy. As our report indicates,
we have used radiation selectively in this group. We have
very limited enthusiasm for the probability that neoadjuvant or continuous hormone therapy will provide survival
benefit in these patients, but agree that from our data
and that presented by others,men with high grade adenocarcinoma of the prostate would be an ideal group for
evaluatinga variety of adjuvant and neoadjuvant therapy.
However, until randomized trials prove otherwise, a
man’s best chance for long term, cancer free survival for
a clinically localized carcinoma of the prostate remains
radical prostatectomy. This opinion is supported by several reports, including those evaluated for quality-adjusted life years stratified by Gleason score? Specifically,
the younger the man and the more poorly differentiated
the carcinoma, the greater the benefit of radical surgery.
Therefore, it is our bias that men with a 10-yearor greater
life expectancy with poorly differentiated prostate cancer
clinically localized to the prostate should not be excluded
from potentially curative therapy, although the expectations for cure are diminished. Finally, although our study
is almost entirely void of serum PSA selected tumors,
recent information from the Physicians’Health Study indicates that aggressive cancers can be detected years earlier through serum PSA testing4 This may translate into
earlier detection,lower stage at detection, and, ultimately,
into improved outcomes for this group of men at high
risk for prostate cancer specific death.
1. Chodak GW, Thisted RA, Gerber GS, Johansson JE, Adolfsson J,
Jones GW, et al. Results of conservative management of c h i c d y localized prostate cancer. N Engl J Med 1994;330:242-8.
2. Partin AW, Lee BR, Carmichael M, Walsh PC, Epstein JI.
Radical prostatectomy for high grade disease: a reevaluation.
J Urol 1994; 151:1583-6.
3 . Fleming C, Wasson JH, Albertsen PC, Barry MJ, Wennberg
JE. A decision analysis of alternative treatment strategies for
clinically localized prostate cancer. JAMA 1993;2692650-58.
4. Gann PH, Hennekens CH, Stampfer MI. A prospective evaluation of plasma prostate-specific antigen for detection of
prostate cancer. JAMA 1995;273:289-94.
Michael G. Oefelein, M.D.
John T. Grayhack, M.D.
Kevin T. McVary, M.D.
Department of Urology
Northwestern University
School of Medicine
Chicago, Illinois
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