Prostate is an accessory gland of male reproductive system situated in the pelvis beneath the urinary bladder and anterior to the rectum. It is about the size of a walnut in young males. Its size increases with age, with most rapid increase occurring after puberty (under the inﬂuence of androgenic hormones, especially testosterone) until the age of 30 years, approximately.
It provides the passage for urethra through its center and contributes about 25% to the volume of the ejaculate. It also provides a passage for the ejaculatory ducts of the seminal vesicles (a pair of glands situated behind the prostate), which drain their secretions (that make-up most of the semen volume) into the prostatic urethra.
It consists of mainly 3 zones: a transition zone (surrounding the urethra and constituting about 10% of the prostate); a central zone (surrounding the ejaculatory ducts and constituting around 25% of the prostate); and a peripheral zone (incompletely covering the other two zones and constituting bulk of the prostate).
Adenocarcinoma (affecting secretory cells of the prostate) is the most commonly encountered (more than 95% of all cases) prostate cancer.
What is the Staging of Prostate Cancer?
TNM is the most commonly used staging system for prostate cancer.
T1 – Prostate cancer is an incidental diagnosis made on prostate biopsy for some other reason. It is not palpable on DRE or visible on imaging.
T2a – Involves less than one-half of one lobe.
T2b –Involves more than one-half of one lobe.
T2c – Involves both lobes
T3a – Tumor extends outside the prostate capsule but doesn’t involve adjacent organs.
T3b – Tumor extends outside the prostate capsule and involves seminal vesicle.
T4 – Tumor involves the periprostatic structures like rectum, bladder, pelvic wall, perineal body, etc.
In the figure below, it infiltrates into perineal body.
Urinary bladder may be involved when prostate cancer infiltrates superiorly.
It may infiltrate posteriorly to involve the rectum.
And lateral infiltration may involve the pelvic wall.
N0 – Nearby lymph nodes not involved
N1 – Regional lymph nodes involved by tumor
M0 – No spread of tumor to distant body parts
M1 – Spread to a distant body parts such as bones, lungs, liver, brain, etc.
What is Gleason’s Score?
Gleason scoring system is based on the extent of abnormality observed in the collected biopsy samples where score of specimen with most predominant Gleason score is added to the highest Gleason score observed, to give overall Gleason score (that may range from 6 to 10).
Further, Gleason grade groups (1 to 5) is calculated as below:
|Gleason Grade Group||Gleason Score||Gleason Pattern|
|4||8||4+4, 5+3, 3+5|
|5||9 or 10||4+5, 5+4, 5+5|
How is the final stage of Prostate Cancer determined?
The final stage is calculated based on TNM staging, PSA levels, and Gleason’s Grade group, as shown in the table below.
|Stage||TNM Score, PSA (ng/mL), Grade Group (GG)|
|I||T1a-2 N0 M0 PSA<10 GG=1|
|IIA||T1a-2a N0 M0 PSA>/=10,<20 GG=1|
|T2b-2c N0 M0 PSA<20 GG=1|
|IIB||T1-2 N0 M0 PSA<20 GG=2|
|IIC||T1-2 N0 M0 PSA<20 GG=3-4|
|IIIA||T1-2 N0 M0 PSA>/=20 GG=1-4|
|IIIB||T3-4 N0 M0 Any PSA GG=1-4|
|IIIC||Any T N0 M0 Any PSA GG=5|
|IVA||Any T N1 M0 Any PSA Any GG|
|IVB||Any T Any N M1 Any PSA Any GG|
What is the Treatment of Hormone Sensitive Prostate Cancer?
The prostate cancer treatment depends on patient’s performance status, life expectancy, comorbidities, stage of the disease, along with other factors.
For hormone naive disease, the treatment decision is taken based on the risk of the disease.
Very Low to Low-Risk Disease
T1a-2 N0 M0, PSA<10, GG=1
Active surveillance is the preferred treatment approach in such cases.
T2b-2c N0 M0 PSA<20 GG=1 TO T1-2 N0 M0 PSA<20 GG=3-4
Active surveillance is the preferred treatment for elderly, comorbid patients with less than 10 years of life expectancy.
Whereas, radical prostatectomy and/or radiotherapy is recommended for younger patients with good performance status and better life expectancy.
Androgen deprivation therapy may also be required in some cases.
Chemotherapy is also an option for some cases.
T1-2 N0 M0 PSA>/=20 GG=1-4 TO Any T N0 M0 Any PSA GG=5
In high risk disease, radical prostatcetomy or radiotherapy is the standard treatment. Androgen deprivation therapy may be added.
Chemotherapy is also an option for some cases.
In case of an elderly patient with poor life expectancy, androgen deprivation therapy or active surveillance may be considered.
Low volume metastasis can be treated with androgen deprivation therapy with or without radiotherapy. Chemotherapy may also be considered.
For high volume metastatic disease with a vast spread of disease to distant organs, chemotherapy plus androgen deprivation therapy is the standard treatment.
What is the difference between Observation and Active Surveillance?
These are the options mainly in early stages of disease.
Observation is preferred when the life expectancy of the patient is less than 10 years. PSA is done every 6 to 12 months for an initial 5 years, and then annually.
Active surveillance is done when the life expectancy of the patient is more than 10 years. In this, PSA is done every 6 months and DRE, prostate biopsy and MRI pelvis are done annually.
What is the role of Androgen Deprivation Therapy (ADT) or Hormonal Therapy in Prostate Cancer?
Hormonal therapy, also known as androgen suppression therapy or androgen deprivation therapy (ADT), is one of the most effective and most widely used therapy option for Prostate cancer. Hormonal therapy consists of various drugs that act by decreasing the concentration of androgens in the blood or by inhibiting the stimulatory action of androgens on the prostate cancer cells.
ADT is the most commonly used primary systemic therapy for the management of localized or advanced prostate cancer. It can be employed as neoadjuvant (prior to surgery or radiation), concomitant (in combination with surgery or radiation), or adjuvant (after surgery or radiation) therapy for the management of locally advanced or metastatic (that has spread to distant body parts like bones, liver, lungs, or brain) prostate cancers.
GnRH agonists/antagonists (Leuprolide, Goserelin, Dagarelix)
These act on the pituitary gland and prevent the release of LH/FSH and ACTH as shown in the figure below.
Cytochrome 17P Inhibitors
These prevent the release of testosterone from testes and adrenal gland as shown below. Cytochrome P450 type 17(CYP17), an enzyme required for the secretion of androgen from the adrenal glands. Cytochrome 17P Inhibitors prevent the release of testosterone from testes and adrenal gland as shown below.
Abiraterone has been approved, in combination with low-dose prednisone, for the treatment of the asymptomatic patients with metastatic CRPC who have not received prior chemotherapy or patients with metastatic CRPC who have initially received the docetaxel-containing chemotherapy.
Androgen Receptor Blockers (Bicalutamide, Nilutamide, Enzalutamide)
These prevent the binding of testosterone on androgen receptors on prostate cancer cells, thereby reducing their growth and survival.
Enzalutamide has been approved as the first-line treatment for the asymptomatic patients with metastatic CRPC who have not received prior chemotherapy or subsequent-line treatment for patients who have received prior docetaxel-containing chemotherapy.
What are the Immunotherapy options available for Prostate Cancer?
Immunotherapy act by stimulating the immune system to kill and destroy cancer cells. It is a type of cancer treatment that enhances the body’s own immune system to fight effectively against cancer. Following are the immunotherapeutic agents which are approved for the treatment of advanced-stage prostate cancer.
It is the only approved cancer vaccine for the treatment of prostate cancer. Similar to conventional vaccines that stimulate the immune system to fight against specific infections, Sipuleucel-T stimulates the immune system to attack the prostate cancer cells. It is an autologous vaccine, that is, it is made from man’s own immune cells.
The patient’s white blood cells are first removed using a process called leukapheresis. The cells are then exposed to prostatic acid phosphatase (PAP), a glycoprotein enzyme normally produced by the prostate cells, which is usually elevated in patients with metastatic prostate cancer and is generally associated with poor prognosis. The cells are then infused back to the patient. This process is generally repeated 2 more times, 2 weeks apart, to deliver a total of 3 doses. The modified white blood cells attack and kill the prostate cancer cells.
Sipuleucel-T has been approved for the treatment of asymptomatic or minimally symptomatic patients with metastatic CRPC with no liver metastases, life expectancy >6 months, and ECOG performance status 0-1 (overall in good health).
It is an anti-PD1 antibody or commonly known as an immune-checkpoint inhibitor. It acts by preventing the interaction of immune-checkpoint with its ligands and thereby removing the breaks from the immune cells that attack and kill the cancer cells.
It has been approved for the treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair (MMR)-deficient solid tumors (including prostate cancer) who have progressed on prior treatment and who do not have a satisfactory alternative treatment option available.
What is the Treatment for Castrate (Hormone) Resistant Prostate Cancer?
The figure below shows the natural history of prostate cancer, and the THIRD peak correlates with hormone resistant prostate cancer (CRPC). When despite on treatment with ADT, there is a disease progression, it is called as CRPC.
If it a localised CRPC, we have the options of observation or Androgen Deprivation Therapy with a different agent as used previously.
In a metastatic CRPC, options are chemotherapy or Androgen Deprivation Therapy.
Best Prostate Cancer Specialist in Delhi
Dr Sunny Garg is a renowned Medical Oncologist in New Delhi with an experience of more than 6 years of treating prostate cancer patients. He has practiced in leading cancer hospitals in Delhi, and currently practicing at Manipal Hospital, Dwarka.
He has a vest experience of treating colon cancer patients in all stages of disease. He is well versed with Immunotherapy, Targeted therapy, and Chemotherapy for Prostate Cancer treatment and also general supportive care for patients. He works in close collaboration with surgical and radiation oncologists, oncopathologists, nuclear medicine, and genetic counselors for comprehensive cancer care for the patients.
Call +91 9686813020 for appointment.