Case 21-2004 A 63-Year-Old Man Castration

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Case 21-2004: A 63-Year-Old Man

with Metastatic Prostate Carcinoma
Refractory to Hormone Therapy
Donald S. Kaufman, M.D., W. Scott McDougal, M.D., Anthony L. Zietman, M.D.,
Mukesh G. Harisinghani, M.D., and Robert H. Young, M.D.
presentation of case
A 63-year-old man was evaluated in the clinic because of metastatic prostate cancer
that was no longer responding to hormone therapy.
The patient had been well until eight years before he came to the clinic, when he had
noticed a decreased urinary stream and urinary hesitancy. A test for prostate-specific
antigen (PSA) six months later showed a level of 2.7 ng per milliliter; six months after
that, the PSA level was 7.7 ng per milliliter. A transrectal needle biopsy of the prostate
showed adenocarcinoma, Gleason grade 3 to 4 (on a scale of 1 to 5, with 1 indicating
low-grade carcinoma, and 5 high-grade carcinoma), involving all the biopsy cores (Fig.
1A and 1B). Computed tomographic (CT) scans of the abdomen and pelvis and a bone
scan showed no abnormalities. The general physical examination also showed no abnormalities. Rectal examination revealed a firm, nodular area, 2 to 3 cm in diameter, that
involved the left lobe of the prostate and that appeared to go to the edge of the gland. The
right lobe was diffusely firm. Laboratory studies and chest radiographic studies showed
no abnormalities.
Two months later, the patient was taken to the operating room for a radical prostatectomy. On intraoperative examination of specimens obtained by bilateral pelvic lymphnode biopsy, involvement by metastatic prostate cancer was grossly evident (Fig. 1C).
The procedure was terminated, and the prostatectomy was not performed. After the
operation, the patients disease was staged as T2N2M0 (a tumor that is palpable or visible on ultrasound, involves both lobes, is associated with more than one positive regional lymph node, and is not accompanied by distant metastases). He was discharged, and
treatment with flutamide at a dose of 250 mg three times daily was prescribed. Two
months later, the patients PSA level was 1.1 ng per milliliter. External-beam radiation
treatments were administered, with a total dose of 69.4 Gy, and were completed six
months after the initial diagnosis.
At that time, the patients PSA level was 0.5 ng per milliliter, and it remained at or below that level for the next six years while he continued taking flutamide. Magnetic resonance imaging (MRI) of the lumbar spine that was performed four years after the diagnosis showed no abnormalities, and the results of all liver-function tests were normal.
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From the Division of Medical Oncology, Department of Medicine (D.S.K.), and the Departments of Urology (W.S.M.), Radiation
Oncology (A.L.Z.), Radiology (M.G.H.), and
Pathology (R.H.Y.), Massachusetts General
Hospital; and the Departments of Medicine (D.S.K.), Urology (W.S.M.), Radiation
Oncology (A.L.Z.), Radiology (M.G.H.),
and Pathology (R.H.Y.), Harvard Medical
School.
N Engl J Med 2004;351:171-8.
Copyright 2004 Massachusetts Medical Society.
july 8, 2004
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larged lymph node in the right retrocrural area (Fig.

3A). A CT scan of the chest showed multiple pulmonary nodules and mediastinal and left hilar lymphadenopathy, which were thought to represent metastatic disease (Fig. 4A).
discussion of management
CC
Figure 1. Biopsy Specimens of the Prostate and a Paraaortic Lymph Node

(Hematoxylin and Eosin Stains).
The initial, diagnostic biopsy specimen obtained contains extensive adenocarcinoma with several patterns (Panel A, 31). A large glandular pattern and a focal
cribriform pattern, graded as Gleason 3C/5 was prominent, but there were also
small fused glands (Gleason grade 4/5) (Panel B, 250), for a Gleason score of
7/10. The lymph-node biopsy specimen obtained at laparotomy (Panel C, 31)
contains a large nodule (Gleason grade 4/5 adenocarcinoma) with a fused glandular pattern, similar to that seen in some areas of the prostate.
Five and a half years after the diagnosis, a bone scan

showed no abnormalities. Six years after the diagnosis, the patients PSA level was 0.2 ng per milliliter.
Eleven months later, the PSA level was 0.9 ng
per milliliter; one month after that (seven years after the initial diagnosis), it was 1.4 ng per milliliter.
The daily flutamide treatment was discontinued.
One month later, a bone scan showed increased uptake at the T11 vertebra, which was suggestive of
metastatic disease, but an MRI scan showed no abnormalities. Over the next five months, the patients
PSA level rose to 4.0 and then to 6.6 ng per milliliter.
An abdominopelvic CT scan showed newly enlarged
retroperitoneal lymph nodes, which were thought to
represent metastatic disease. A bone scan showed
no metastatic disease.
One month later, leuprolide by intramuscular injection was begun at an initial dose of 7.5 mg, followed one month later by 22.5 mg, which was then
given every three months. Four months later, the
PSA level was 6.4 ng per milliliter. A bone scan obtained one month later showed metastatic disease
at T10, L5, the right humerus, and the ribs bilaterally (Fig. 2A). An abdominopelvic CT scan obtained the same day showed progression of the
retroperitoneal lymphadenopathy and a newly en-
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Dr. Donald S. Kaufman: Over a span of eight years, this

man has been cared for by urologists, radiation oncologists, and medical oncologists, and his care has
included prostate biopsies, an exploratory laparotomy, radiation treatment, and hormone therapy. Each
of these treatment decisions required a riskbenefit
analysis, from his initial presentation with an elevated PSA level, when the primary treatments considered included radical prostatectomy and intensive radiation treatment, to his current evaluation,
when a decision about the use of chemotherapy had
to be made in the context of widespread disease.
Dr. Young, would you show us the slides of the
specimens from the initial prostate biopsy?
Dr. Robert H. Young: Most of the cores were extensively involved by adenocarcinoma, even more extensively on the left side than on the right side. The
pattern was not that of the usual small acinar adenocarcinoma that is seen in 80 to 90 percent of prostate
cancers, but rather a pattern of larger glands. Some
areas were well differentiated and were classified as
Gleason grade 2, and some were Gleason grade 3C,
with a cribriform pattern (Fig. 1A). Some clinicians
believe that Gleason grade 3 carcinomas with a cribriform pattern have a somewhat worse prognosis
than Gleason grade 3 adenocarcinomas without a
cribriform pattern. In other areas, there were fused
small glands in a packed, microacinar pattern typical of a Gleason grade 4 adenocarcinoma (Fig. 1B).
The Gleason score, as opposed to grade, was 7 (the
sum of the two highest grades, in this case 3 and 4).
management of localized prostate cancer
Dr. Kaufman: At the time of his initial presentation,

the patient appeared to have cancer localized to the
prostate. The treatment options included radical
prostatectomy and radiation therapy. I would like to
ask Drs. McDougal and Shipley to discuss the roles
of radical prostatectomy and radiation therapy in the
curative treatment of this patient.
Radical Prostatectomy
Dr. W. Scott McDougal: Radical prostatectomy has several advantages: examination of the specimen offers
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definitive knowledge of the pathological stage and

grade of the disease, and the patient benefits from
what I consider the most durable method of disease
eradication over the long term. Patients may be stratified according to the pathological stage of their disease. If the Gleason score is 2 to 4 and the clinical
stage is T1c (i.e., the patient has an elevated PSA level without a palpable mass), the progression-free
survival rate after a radical prostatectomy is approximately 90 percent; if the Gleason score is 5 to 6,
the rate is about 80 percent; if the score is 7, the rate
is about 55 percent; and if the score is 8 to 10, the
rate is less than 20 percent.1 For patients who have
T2 disease, such as the patient under discussion, the
probability of 15 years of progression-free survival
is approximately 69 percent. The higher the Gleason score, and the more extensive the disease, the
greater the likelihood of intraoperative and postoperative complications. Intraoperative complications
include bleeding and injury to the obturator nerve,
the urethra, the rectum, or a major pelvic artery or
vein. Postoperative complications may substantially alter the patients quality of life; they fall into
three categories: incontinence, impotence, and urethrovesical stricture.
The incidence of complications reported by primary caregivers in single-institution studies tends
to reflect better results than the incidence reported
by investigators who are not the primary caregivers
in large, multi-institution studies. The incidence of
urethrovesical stricture, for example, varies from
less than 1 percent to 9 percent. The incidence of
incontinence in single-institution studies is about
8 percent, with 6 percent of the patients having
stress incontinence and 2 percent wearing more
than one pad a day. In assessments of incontinence
in multi-institutional studies one year after the surgery, about one third of the patients are reported to
wear a pad.2 Potency rates also vary, depending on
who asks the question of the patient, the age of the
patient, and the patients erectile status before the
operation. In studies in which the patients own assessment is used, potency rates vary from 90 percent
in patients less than 50 years of age to 25 percent in
those greater than 70 years of age.3 However, when
patients are assessed with the use of appropriate
outcome measures by a disinterested third party in
multi-institutional studies, only 31 percent of patients report that they have an erection and only
9 percent report successful intercourse.2 In a population-based study of 1291 men who were evaluated 18 or more months after radical prostatectomy,
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Figure 2. Bone Scans Obtained before and after Chemotherapy.

A scan obtained 7 years and 10 months after the diagnosis (Panel A) reveals
metastatic lesions (arrows) in the lower thoracic and lumbar spine. Seven
weeks after the initiation of chemotherapy (Panel B), the lesions show increased activity (arrows). This flare phenomenon results from an increase
in osteoblastic activity in healing bone lesions.
8 percent were incontinent and 60 percent were

impotent.4
This patient was thus a good candidate for radical prostatectomy, and at the age of 55 years, he had
a low risk of side effects.
Radiation Therapy
Dr. William U. Shipley (Radiation Oncology): The advantages of external-beam radiation therapy as the
primary treatment for this patient with localized
prostate cancer are that it poses a very low risk of
urinary incontinence and stricture; it may eradicate
extensions of the tumor beyond the capsule of the
prostate; and when it is combined with hormonal
therapy, it may offer a chance of cure for some patients, such as this one, with intermediate-risk tumors. The disadvantages of radiation therapy are
that the treatment is long, eight to nine weeks; a
three-dimensional, conformal technique that allows the delivery of doses of at least 72 Gy may be
required; and the treatment adds a low risk of subsequent rectal symptoms. In addition, this therapeutic method does not inform the clinician about
possible metastases to lymph nodes, and the longterm sequelae of ultrahigh-dose radiation treatments are not known.
The chance of recurrence-free survival after irradiation, with the use of post-treatment PSA level as
the monitoring criterion, can be predicted by the
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Figure 3. Axial CT Images of the Abdomen Obtained

after the Intravenous Administration of Contrast Material.
A CT image obtained 7 years and 10 months after the diagnosis reveals an enlarged lymph node close to the aortic bifurcation (Panel A, arrow). An image from a repeated
CT scan obtained at the same level seven weeks after the
initiation of chemotherapy shows diminution in the size
of the pelvic lymph node (Panel B, arrow).
risk group of the patient at presentation. For patients with low-risk tumors (stage T1c, a Gleason
score of 6 or less, and a PSA level of 10 ng per milliliter or less), the rate is 70 to 80 percent.5 This patient had an intermediate-risk tumor (stage T2 tumor, Gleason score 7, and an initial PSA level of 10
to 20 ng per milliliter), and his expected chance of
survival would range from 50 to 55 percent if he
were given conventional external-beam radiation
therapy alone.
Over the past decade, the development of threedimensional conformal therapy, which uses computer software to integrate CT images of the pa-
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Figure 4. Axial CT Images of the Chest Obtained

after the Intravenous Administration of Contrast Material.
An image obtained seven years and eight months after
the diagnosis shows multiple nodules in both lungs
(Panel A, arrows). An image obtained seven weeks after
the initiation of chemotherapy shows a decrease in size
and cavitation of some of the nodules (Panel B, arrows).
tients internal anatomy in the treatment position,

has allowed the volume of tissue to which a high
dose of radiation is delivered to conform more exactly to the shape of the tumor. This advance has
reduced the incidence of both early and late toxic
effects on normal tissue in patients with prostate
cancer and allows higher cumulative doses to be
delivered with a reduced risk of late effects.6,7 There
is now evidence from both randomized and nonrandomized clinical trials of significant improvement
in the rates of recurrence-free survival in patients
with intermediate-risk tumors when doses greater than 70 Gy are used.8-10 In addition, patients who
have intermediate-risk tumors have significantly
higher disease-specific survival rates with a short
course of neoadjuvant androgen-suppression therapy and radiation treatment than they do with radiation treatment alone.10
Thus, the current recommendation for this pa-
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tient would be irradiation to a total dose of 75 to

76 Gy by the three-dimensional conformal technique, preceded by a short course of neoadjuvant
androgen suppression. In recent reports, the rates
of disease progression 6 to 10 years after irradiation are similar to those in reports of series of patients undergoing prostatectomy.8,11
Strict contraindications to external-beam radiation therapy include prior pelvic irradiation, active
inflammatory bowel disease, a permanent Foley
catheter, and morbid obesity. For this patient, who
had none of these problems, radiation therapy is a
reasonable alternative to radical prostatectomy.
Dr. Kaufman: Both radical prostatectomy and
conformal external-beam radiation treatment can
cure localized prostate cancer; cure is more likely
for patients with low-risk disease than for patients
in the intermediate-risk and high-risk groups. The
incidence of serious incontinence after radical prostatectomy is about 5 percent when the procedure is
performed by experienced surgeons and virtually
nonexistent after radiation treatment; the rate of impotence is about 50 percent after either treatment.
Not surprisingly, surgeons prefer prostatectomy
and radiation oncologists favor irradiation as the
treatment of choice.12 No prospective comparative
study of conformal external-beam radiation treatment with higher total doses of radiation and surgery has been reported.
After consultation with his physicians, this patient chose to undergo radical prostatectomy. At laparotomy, enlarged pelvic lymph nodes were seen.
Dr. Young, would you describe the specimens for us?
Dr. Young: On intraoperative gross examination,
the three right obturator lymph nodes sampled were
rubbery in texture and ranged from 0.5 to 2.0 cm in
greatest dimension; the single left obturator lymph
node was 1.4 cm in its greatest dimension and contained a nodule of firm, tan-to-white tissue, a finding indicating the presence of tumor. On microscopical examination of both frozen and permanent
sections (Fig. 1C), the tumor had a small, acinar,
fused glandular pattern similar to that seen in the
prostate biopsy specimen. Two of the three lymph
nodes on the right side and the one on the left side
contained cancer.
Dr. Pablo Gomery (Urology): Because the biopsy

had revealed a rather poorly differentiated prostatic
carcinoma and examination of several lymph nodes
had shown grossly evident carcinoma, I believed
that the likelihood of a cure for this patient by prostatectomy was low and did not justify the potential
complications of the operation in a man of his age
who was sexually active, so I terminated the procedure without completing the prostatectomy.
Dr. Kaufman: Dr. Zietman, what is the role of radiation treatment in this patient, who had positive
nodes and in whom surgery was aborted?
Radiation Therapy
Dr. Anthony L. Zietman: More than 90 percent of patients who have node-positive prostate cancer have
occult metastatic disease elsewhere. As a consequence, cure is unlikely with any localized therapy.
Many patients, however, have bulky or aggressive
disease at the primary site, which may cause local
symptoms and may be the first site of tumor progression. Two studies, one from the M.D. Anderson
Cancer Center13 and one from this institution,14
found that in patients treated with androgen deprivation alone, the primary site was the most common
first site of progression, requiring subsequent local therapy in up to 73 percent of the patients. In
contrast, of the patients treated with both androgen
deprivation and local therapy (radiation therapy or
transurethral prostatectomy), local recurrence of
disease requiring therapy developed in 11 percent
or less.
Local therapy plus androgen deprivation may
therefore be justified to extend the initial diseasefree interval and to reduce symptomatic local progression. In this patient, I recommended radiation
therapy; this was before the days of three-dimensional conformal treatment, and he received what
was then our standard dose approximately 69 Gy.
Dr. McDougal: The fact that you treated him locally does not necessarily mean that you eradicated
the local disease or eliminated the possibility of local progression.
Dr. Zietman: Absolutely not.
Dr. Kaufman: The patient did not experience any
local side effects from the radiation therapy, and he
stated that his sexual potency was unaffected. He
management of locally advanced
was free of symptoms for seven years after the diprostate cancer
agnosis; then, while he was receiving flutamide,
Dr. Kaufman: Dr. Gomery, you were the surgeon car- the PSA level rose to 0.9 ng per milliliter and then
ing for this patient. Please tell us what you did and to 1.4 ng per milliliter. The flutamide was disconthe reasons for your decisions.
tinued. Intramuscular leuprolide was begun six
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months later, but the PSA level continued to rise.

A bone scan and chest and abdominal CT scans
were obtained four months later.
Dr. Mukesh G. Harisinghani: The bone scan at this
time (Fig. 2A) shows areas of increased uptake in
T10, the ribs bilaterally, and the right humerus. Images from a contrast-enhanced CT scan of the abdomen and pelvis (Fig. 3A) show newly enlarged
retroperitoneal lymph nodes adjacent to the upper
and lower abdominal aorta and the bifurcation
a finding that probably represents metastatic disease. The lung windows from the chest CT scan
(Fig. 4A) show multiple nodules in both lungs, and
the mediastinal windows show enlarged precarinal
and subcarinal lymph nodes; all of these findings
almost certainly represent metastatic disease.
Dr. Kaufman: What are the treatment options at
this point? The patient has been receiving leuprolide
for four months, with no improvement. Dr. Smith,
would you discuss hormone treatment for advanced
prostate cancer?
Hormonal Therapy
Dr. Matthew R. Smith (Hematology/Oncology): Androgen-deprivation therapy by either bilateral orchiectomy or administration of a gonadotropinreleasing hormone agonist such as leuprolide is
the mainstay of treatment for advanced or metastatic prostate cancer. Androgen-deprivation therapy by
either method decreases serum testosterone levels
by more than 95 percent and leads to objective responses in the majority of patients. Monotherapy
with antiandrogens is an alternative to standard androgen-deprivation therapy. Flutamide is a nonsteroidal antiandrogen that blocks the action of testosterone by binding to the androgen receptor in target
tissue. This mans disease responded to flutamide
monotherapy for more than six years. About two
thirds of men with progressive disease who receive
antiandrogen monotherapy will respond to subsequent androgen-deprivation therapy. The long duration of the response to flutamide monotherapy in
this case suggests a higher-than-average chance of
a response to subsequent medical or surgical castration. In addition, in a few men treated with a
gonadotropin-releasing hormone agonist, testosterone levels approaching those achieved by bilateral orchiectomy are not reached. I recommend the
measurement of serum-testosterone levels for patients who either do not have a response or who have
unexpectedly short responses to a gonadotropinreleasing hormone agonist. Bilateral orchiectomy
may prove effective in the men whose testosterone
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production cannot be adequately suppressed with a

gonadotropin-releasing hormone agonist.
Dr. Kaufman: Given the patients progression of
disease while he was receiving hormonal treatment, we considered multiagent chemotherapy.
Dr. Michaelson, would you discuss the role of chemotherapy in the treatment of a patient, such as this
one, who has advanced, hormone-refractory prostate cancer?
Chemotherapy
Dr. M. Dror Michaelson (Hematology/Oncology): The

early experience with cytotoxic chemotherapy in
prostate cancer was largely unsuccessful, and until
the 1990s, chemotherapy was not considered a standard treatment for this disease. Two randomized,
phase 3 studies in the mid-1990s showed a benefit
with mitoxantrone and corticosteroids as compared
with corticosteroids alone, with improvement in the
patients scores on pain scales and in their overall
quality of life.15,16 However, even this combination
produced a decrease in the PSA level in only 30 to 35
percent of the patients. The same studies also failed
to show a benefit in overall or disease-specific survival among patients treated with mitoxantrone and
corticosteroids as compared with those treated with
corticosteroids alone.
Taxane-based regimens have now been studied
in numerous phase 1 and 2 clinical trials, and they
appear to be more promising than previously studied therapies. Paclitaxel and docetaxel alone or in
combination with estramustine, with or without carboplatin and etoposide, have been studied in multiple phase 1 and 2 trials. Many of these trials have
documented response rates in excess of 50 percent.17,18 In response to these data, an Intergroup
phase 3 study comparing docetaxel and estramustine with the current standard therapy, mitoxantrone plus corticosteroids, is under way.
In the past few years, clinical trials have evaluated
the usefulness of adding a third agent to the combination of docetaxel and estramustine. These have
included biologic agents targeted against growthfactor pathways and traditional cytotoxic chemotherapy drugs. At this hospital, my colleagues and
I have conducted a study of a regimen that combines
docetaxel, estramustine, and carboplatin in men
with hormone-refractory prostate cancer. Accrual to
this study has been completed, but the results are
not yet available. The patient under discussion was
enrolled in this trial.
Dr. Kaufman: Eight years after the initial diagnosis, chemotherapy consisting of docetaxel, estra-
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mustine, and carboplatin was initiated, carried out

for six cycles, and completed in six months. During
the six months of chemotherapy, the patient had virtually no symptoms except for very mild fatigue. He
did not miss work and was able to continue his activity of mountain climbing. His PSA level dropped to
0.5 ng per milliliter shortly after the start of chemotherapy, and at the completion of chemotherapy his
PSA level was less than 0.2 ng per milliliter.
Dr. Harisinghani, would you show us the images
that were obtained after the treatment?
Dr. Harisinghani: On the bone scan obtained seven
weeks after the start of chemotherapy (Fig. 2B), the
preexisting lesions all showed increased activity.
This phenomenon, which has been called a flare,
represents increased osteoblastic activity within the
metastases, which is a sign of improvement after
treatment. No new lesions were identified. The
paraaortic lymphadenopathy has regressed in size
as compared with that seen on the previous abdominal CT scan (Fig. 3B). A chest CT scan obtained at
the same time reveals that the pulmonary nodules
have regressed in size (Fig. 4B) and show some cavitation, indicating a response to therapy. The mediastinal nodes have all decreased in size.
Dr. Kaufman: These images illustrate an important point. When the patients chest and abdominal
CT scans showed that there had been dramatic improvement, the bone scan was initially read as revealing an increase in metastatic disease. On review,
however, it became clear that this finding was a flare
reaction all of the increased uptake was in areas
that had previously been involved by tumor. This is
a rare phenomenon that occurs as a result of treatment, and it is important to recognize.
Unfortunately, four months after the completion
of chemotherapy, the patients PSA level began to
rise, and three months later nine years after the
initial diagnosis and one year after the initiation of
chemotherapy it was 6.3 ng per milliliter. Repeated CT scans revealed stable lung nodules. An
abdominopelvic CT scan showed an increase in the
size of the left paraaortic lymph nodes. A bone scan
showed a new lesion in the T9 vertebral body and a
lesion in T10 that had increased in size.
Because of his good response and because he did
not have a toxic reaction to the chemotherapy regimen, we decided to treat him again, using the same
agents. At the time of the first chemotherapy visit,
he reported smoky vision in his left eye, with no gait
disturbance or headaches. He was evaluated by a
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vitreoretinal specialist, who conducted fluorescein

testing, indocyanine green angiography, and optical
coherence tomography; a 1-mm area of thickening
was observed, a finding consistent with a single choroidal metastatic lesion on the left retina. After one
cycle of chemotherapy, the patient noted an improvement in visual clarity. His PSA level decreased
from 6.0 to 3.0 ng per milliliter after the first cycle
of chemotherapy; after seven cycles, his PSA level
was less than 0.2 ng per milliliter.
Dr. Alex F. Althausen (Urology): What is the average duration of tumor-free survival for a patient who
presents with known nodal disease and is given all
these therapies? Is this patients course unusual in
being protracted over nine years? Or, can we tell patients that even if the results of an MRI or CT scan
are positive for cancer, with appropriate chemotherapy they can expect nine or more years of a reasonable quality of life?
Dr. James Talcott (Medical Oncology): This patients long survival is unusual, but the course of
prostate cancer is highly variable, even after adjustments for tumor stage, Gleason score, and PSA level. Earlier diagnosis as a result of PSA screening
has led to a longer survival for all patients, through
stage migration.19 In a small, randomized trial of
immediate hormone treatment as compared with
treatment at the time of clinical relapse in patients,
such as this man, with positive nodes, survival was
improved in the immediate-treatment group,20 but
growing evidence of toxicity from long-term androgen-deprivation therapy suggests that discussion
should precede chemical castration of asymptomatic men without metastases.21
Dr. Kaufman: At the most recent follow-up, the
patients PSA level was 0.2 ng per milliliter. A bone
scan and abdominal, pelvic, and chest CT scans all
showed stable disease. Unfortunately, his eye lesion
recently recurred, and he is now receiving protonbeam therapy to the eye. In the care of this patient
over what is now a 10-year span, we have used almost every known treatment for prostate cancer. Remarkably, the patient has felt well throughout the
entire course of his illness, carrying on with his normal occupation and activities.
anatomical diagnosis
Adenocarcinoma of the prostate with metastases.
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177
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