Carcinoma is the only common tumor of the prostate. Benign tumors are uncommon
and rarely of clinical significance.
Adenocarcinoma
Prostatic adenocarcinoma is the most frequently diagnosed carcinoma in males.
It occurs at an increasing rate with advancing age. It is rare before the
age of 50 years and most patients are over 60 years at the time of diagnosis.
The incidence of detected carcinoma of the prostate has increased dramatically
due to new screening and biopsy techniques.
There are remarkable racial differences in incidence. The disease is rare
in Asians and most common in blacks, who also have the highest death rates
from prostatic cancer.
About 10% of cases are familial, with a significantly increased risk in men
whose first-degree relatives have had the disease. No specific chromosomal
abnormalities have been detected. The vast majority of cases are sporadic.
The cause of prostatic carcinoma is unknown. There is some suggestion but
no proof yet that dietary fat may increase the risk of developing prostatic
adenocarcinoma by influencing levels of testosterone, which in turn affects
the growth of the prostate. There is no evidence of a relationship between
nodular hyperplasia and carcinoma. The role of sex hormones in prostatic carcinoma
is poorly understood. While it is clear that inhibition of prostatic carcinoma
can be achieved with exogenous estrogens and orchiectomy, higher levels of
serum androgens or significant alteration in their metabolism have not been
shown consistently in patients with the disease. The role of androgens in
prostatic carcinoma may be permissive, being required for maintenance of the
neoplastic prostatic epithelium, which like their normal counterparts, have
androgen receptors.
In most cases of prostatic carcinoma, foci of glands lined by dysplastic
epithelium, referred to as prostatic intraepithelial neoplasia (PIN) are seen.
PIN and carcinoma both occur in the peripheral zone and high grade PIN and
invasive carcinoma have similar cytologic features. PIN is presumed to be
the precursor lesion for invasive carcinoma.
Both early and advanced carcinoma of the prostate may be asymptomatic at
the time of diagnosis and in the past more than 80% of patients had advanced
or metastatic disease at the time of diagnosis. With screening programs, which
employ digital rectal examination and serum PSA (see below) measurement, many
prostatic carcinomas are diagnosed at an early stage. Symptoms when present
include dysuria, difficulty of micturition, or increasing urinary frequency,
and others referable to metastatic tumor. Clinically detectable disease usually
manifests as firm to hard, nodular and irregular areas palpated transrectally.
The cut surface of resected specimens shows hard, ill defined, gray to grayish-yellow
nodules.
Histologically, the disease produces well-defined, readily discernable glandular
patterns. The glands are usually small and lined by a single layer of cuboidal
cells and may show papillary or cribriform patterns. Less often the glands
are large and without papillary tufting while in poorly differentiated forms
gland formation is rudimentary or absent. Mixed patterns are common.
Prostatic adenocarcinoma
Prostatic adenocarcinoma. Note single layer epithelium with moderate nuclear
pleomorphism.
Prostatic adenocarcinoma, cribriform pattern.
In others there is no gland formation.
Prostatic adenocarcinoma. Note lack of gland formation.
Several histologic grading systems of prostatic carcinomas have been suggested
because there is fairly good correlation with prognosis independent of the
clinical stage. The combination of pathologic grade and clinical stage allows
even better prediction of prognosis. Although stage and grade are often related
in that high grade tumors tend to present at an advanced stage, this is not
invariably so. Prognosis correlates with stage approximately as follows:
Perineural invasion, although common, has no prognostic significance.
Carcinoma of the prostate spreads by both hematogenous and lymphatic routes.
The tumor spreads through the pelvic lymphatics to the lymph nodes around
the internal and common iliac arteries and the aorta. Hematogenous spread
via the pelvic veins and thence the inferior vena cava occurs late in the
disease and produces systemic metastases. Generally, prostatic carcinoma shows
a tendency to cause bony metastases, particularly to the vertebral column
and pelvic bones, which are osteoblastic (increasing bone density) rather
than osteoclastic (bone destruction).
Pale, osteoblastic metastases in several vertebral bodies.
X-ray of pelvic bones showing osteoblastic metastases.
Question: What is the possible anatomic explanation for the frequent
occurrence of skeletal metastases in the lower vertebral column and pelvic
bones in patients with carcinoma of the prostate?
Answer: There are many connections between the prostatic venous plexus and
the vertebral veins. The veins forming the prostatic plexus do not contain
valves and it is thought that straining to urinate causes prostatic venous
blood to flow in a reverse direction and enter the vertebral veins carrying
malignant cells to the vertebral column.
Biochemical markers for prostatic cancer include prostatic acid phosphatase
and prostatic specific antigen (PSA). Prostatic acid phosphatase is typically
elevated in patients with extraglandular disease and may be followed as a
serum marker of disease progression. It cannot be used to reliably detect
intraglandular (curable) disease at this time. Serum PSA is elevated in most
patients with prostatic carcinoma, including many with disease confined to
the gland. However, PSA is an imperfect marker because of reduced sensitivity
(does not detect all cases of prostatic carcinoma due to false negative results)
and lack of specificity (many false positive cases) as PSA may also be increased
in some benign prostatic conditions such as nodular hyperplasia. Nonetheless,
screening programs are increasingly employing serum PSA estimations, along
with digital rectal examinations, as "first line" measures to identify
patients for further study.
Treatment of prostatic adenocarcinoma is dependent on carcinoma. Surgical
resection of lesions confined to the prostate is often curative. There is
no good therapy for this tumor once it escapes the prostate gland and treatment
for this stage of the disease is usually palliative. This includes a combination
of radiation therapy, androgen deprivation (via use of estrogens or castration),
and, less commonly, other chemotherapeutic agents or limited surgical resections
of recurrent disease. Although the incidence of detected prostatic carcinoma
has increased the mortality from the disease has not increased at all. Also
the true frequency of prostatic cancer is considerably higher than its clinical
incidence. The difference is due largely to higher frequency of occult carcinomas
found at autopsy and specimens resected for nodular hyperplasia or in patients
with marginally elevated PSA levels. These findings suggest that these small
tumors have limited biologic potential and their treatment is therefore highly
controversial. Depending on clinical circumstances (age, co-morbidities, patient’s
wishes, etc), patients may be treated wit follow-up only, interstitial radiation
(radioactive seeds), external beam radiation, or surgical resection (radical
prostatectomy).
