Prostate Cancer Risk Factors Detection Diagnosis and Imaging with PET-CT Scan
Posted By HealthcareOnTime Team
Posted on 2021-09-16
Prostate cancer is the second most common cancer in men worldwide,
and is often described as a disease of the elderly since its peak age of
incidence is 80 years. In India, data regarding the incidence rate of
prostate cancer is limited because this disease is not notifiable and
the number of community based studies on this type of cancer are
limited. However, due to environmental factors and lifestyle changes,
the incidence of prostate cancer in India is expected to rise. One
study carried out in the following cities of India: Ahmedabad,
Bangalore, Chennai, Delhi, Mumbai, Karunagappalli, Nagpur,
Pune, and Thiruvananthapuram, estimated that the age adjusted
incidence rates of prostate cancer in India as a whole to be 3.7
per 1 lakh persons in the year 2008.
These rates clearly show a marked increase in reported cases
of prostate cancer incidence in our country. However, this
could also be due to greater awareness regarding this cancer
which leads to more cases being reported over time and documented.
What is Prostate Cancer?
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The prostate is a small reproductive gland located in males between
the base of the penis and the bladder, just in front of the rectum.
It secretes fluid, that nourishes and hydrates sperm and is excreted
with it as semen. There are several types of cells in the prostate;
cancers most commonly develop in the glandular cells. Prostate
is absent in females, although they do have similar structure
known as Skene's gland.
What are some risk factors of prostate cancer?
Some of the risk factors for developing prostate cancer are:
Age-Aging is the most significant risk factor of prostate cancer.
Being over 50 years old, increases the chances of developing prostate cancer.
Asian-American and Hispanic men are less at risk while African descent,
including African American men have a greater risk of prostate cancer.
Prostate cancer is reported to run in families and therefore has probable
genetic origins. The BRCA1 and BRCA2 genes that are involved in
breast cancer in women, as well as HOXB13 gene are also reported
to play a role in prostate cancer in men.
What is the main cause of prostate cancer?
Prostate cancer has a largely variable natural history, with some
tumors being slow growing while others are highly aggressive.
Tumors which grow slowly do not show significant symptoms
until they reach more advanced stages. As the tumor enlarges,
it may lead to certain signs ta symptoms like frequent urge for
urination, difficulty in urinating, blood
or semen, and
painful ejaculation. Early stage prostate cancer can be treated
successfully in some cases. However, in other cases, prostate
cancer can be very aggressive and can even be life threatening
especially if it undergoes metastasis to other locations. Metastasis
to the bone
is more common, hence advanced prostate cancer
also presents with bone pain and fractures.
How to Detect and Diagnose Prostate Cancer?
It is important to correctly diagnose prostate cancer even before its
symptoms appear, since appearance of symptoms is a characteristic
of advanced disease The most common detection techniques are
digital rectal exam, transrectal ultrasound, and biomarkers.
Some of the common biomarkers used in prostate cancer testing are:
Prostatic Acid Phosphatase (PAP):
PAP was the first biomarker to be used in diagnosis and staging of
prostate cancer. It is secreted by the prostate epithelial cells and
can be measured by immunoassay or enzymatic assay.
Prostate Specific Antigen (PSA test):
PSA is produced by the prostate and secreted into the seminal fluid.
In case of hyperplasia and neoplasia in the prostate gland, the
physiological barriers are disrupted leading to the presence of
PSA in circulation. It is one of the most widely used biomarkers
for prostate cancer screening.
hK2 is a biomarker from the same family as PSA. While PSA is found in
higher amounts in the bound state, hk2 mostly exists in free, unbound form in the serum.
How accurate is PET scan for prostate cancer?
PET-CT scan is one of the most advanced modalities for cancer imaging it
combines the morphological information provided by CT with the
metabolic data given, by PET. PET-CT uses "F-Fluoro-Deoxyglucose
("F-FDG) as a radiotracer to locate and characterize the tumor.
While effective in most cancers, F-FDG in prostate cancer are
not as good due to low glucose metabolic activity of prostate
cancer. F-FDG is therefore only useful in those prostate cancer
patients with high grade, hormone resistant cancers or lesions
which are poorly differentiated. Bone Scan (BS) with Tc Methyl
Diphosphonate (MDP) or other radiolabeled phosphonates are
also presently used either in staging or in restaging to detect
skeletal metastases. However, high uptake of this radiolabel
can also occur due to non-malignant changes in the bones
like trauma and degenerative bone disease, leading to false
positive results. Due to these reasons, the development of
new radiotracers for prostate cancer detection has become critical
What is the difference between Prostate Specific Membrane Antigen (PSMA) and PSA?
PSMA is a transmembrane protein (as opposed to PSA which is
secretory protein), whose levels are elevated 100 to 1000 times
more than normal cells in case of prostate cancer. It is involved in
prostate cancer by supporting cellular growth and proliferation by
increasing folate level in these cells, as it functions as a folate hydrolase.
PMSA is selectively overexpressed in prostate cancer lesions as well as
in bone and lymph node metastases. Since it is a transmembrane protein,
detection of PSMA is done either by using anti-PSMA, monoclonal antibodies,
or other radiolabeled ligands specific to PSMA, which bind to PSMA present
on the surface of prostate cancer cells.
What is Prostate Specific Membrane Antigen (PSMA)?
PSMA expression is directly correlated with cancer aggressiveness, cancer
progression, metastasis, and can serve as an independent indicator of poor
prognosis. Earlier detection of prostate lesions through PSMA based tracers
allows alteration in follow-up treatments. It is also reported to be a predictor
of cancer recurrence in prostate cancer patients, and for cancer staging since
PSMA expression is reported to increase with the stage and grade of the tumor.
Due to these reasons, PSMA has gained popularity as a target for imaging
and treatment of prostate cancer.
Several PSMA targeted PET tracers have been developed that have shown
good results in staging and restaging of prostate cancer, even when PSA
levels are found to be low. PMSA has both diagnostic and therapeutic
value because this ligand is internalized into the cell via clathrin mediated
endocytosis, which can be used as a mode to transport anticancer therapeutic
agents into the cancer cell. Some of the most widely used PSMA agents are
therefore theranostic (therapeutic and diagnostic) agents, such as
PSMA-617 labeled with either "Ga or "Lu, and "GaPSMA-11.
In addition to diagnostic and therapeutic applications, PSMA can
also be used in radio-guided surgery since PSMA-based tracers could
provide real-time information to the surgeon regarding resection
margins and extent of the disease. This is especially effective
in cases when residual disease or micrometastases could not
be completely removed during surgery as they are harder to identify
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Future Perspectives of PSMA in Cancer Imaging
the future of PMSA based cancer imaging is in the development of
new tracers that target PSMA. One example of a promising radiotracer is
pentanedioic acid) ("F-DCFPyL). This agent has higher tumor to background
uptake which helps in detection of metastasis better than conventional
modalities. Aside from its greatest application in patients with recurrent
prostate cancer with low PSA levels, PSMA appears promising in the
detection and characterization of primary tumors, local staging of
regional lymph nodes, and the identification of metastatic
disease for targeted treatment.
This modality is yet to be established in assessing treatment response,
hence development of novel imaging response criteria is needed.
Considering the promising results of PSMA based therapy for prostate
cancer, individualization of therapy based on tumor characteristics can also be explored.