The prostate cancer treatment depends on many factors including the patient’s performance status, life expectancy, comorbidities, overall stage assigned to the disease, along with other factors. Following are the preferred treatment approaches for different stages of prostate cancer, but the final decision is taken after clinical assessment of the patient by an oncologist.
|Stage||TNM Score, PSA (ng/mL), Grade Group (GG)||Preferred Treatment|
|I||T1a-2 N0 M0 PSA<10 GG=1
(Very Low to Low-Risk Disease)
|Stage I disease do not produce any symptoms and most studies suggest that active surveillance is the best approach in such cases. The patient should be screened frequently for any sign of disease progression. No other treatment is generally recommended.|
|II||T2b-2c N0 M0 PSA<20 GG=1
T1-2 N0 M0 PSA<20 GG=3-4
|As with Stage I disease, active surveillance is the first choice of treatment for elderly patients with other complications and whose life expectancy is less than 10 years.
For younger patients without any other health issue, radical prostatectomy (surgical removal of the prostate gland) and/or radiotherapy is generally recommended. In case of high PSA level or high Grade group, androgen deprivation therapy may also be employed to prevent disease recurrence.
|III||T1-2 N0 M0 PSA>/=20 GG=1-4
Any T N0 M0 Any PSA GG=5
|For Stage III disease, radiotherapy in combination with androgen deprivation therapy is considered as the standard treatment.
Radical prostatectomy followed by removal of pelvic lymph nodes and radiotherapy may also be considered.
In case of an elderly patient, less intense treatment is generally recommended. Such patients can be treated with androgen deprivation therapy alone or active surveillance may be considered if life expectancy is very low.
|IV||Any T N1 M0 Any PSA Any GG
Any T Any N M1 Any PSA Any GG
|Low volume stage IV disease with limited spread of disease to bones can be treated with androgen deprivation therapy with or without radiotherapy as standard treatment.
For high volume Stage IV disease with a vast spread of disease to distant organs, chemotherapy plus androgen deprivation therapy is considered as the standard treatment.
Further treatment can be given based on the response from the initial treatment.
Palliative therapy like transurethral resection of the prostate (TURP) for bleeding and urinary obstruction or a bisphosphonate/radiopharmaceutical treatment to manage bone pain /disease can also be employed as and when required.
Following is the brief description of various treatment types employed for prostate cancer:
Surgery: Surgery is a treatment choice for non-metastatic prostate cancer cases, depending upon stage of the disease, life expectancy, risk group, along with other factors. For an early-stage disease where the tumor is confined to the prostate, a radical prostatectomy can be performed. In this procedure, the entire prostate along with the seminal vesicles, and regional lymph nodes is removed. It can be performed either as an open surgical procedure or by using a laparoscopic technique.
Transurethral resection of the prostate (TURP): A transurethral resection of the prostate can be performed to relieve urinary obstruction. This approach is generally adopted for an advanced-stage disease. In this technique, an instrument called resectoscope is passed through the urethra up to the prostate, and the prostate tissue is resected/destroyed with the help of a high-energy laser or electric current.
Radiation Therapy: Radiation therapy (or radiotherapy) uses high-energy radiation directed to the affected area to kill cancerous cells. It can be employed either by using an external radiation source (external beam radiation therapy) or by directly placing the source of radiation near the cancer tissue (brachytherapy). It is commonly used as the first-line treatment option for early-stage prostate cancer because it has efficacy similar to that of prostatectomy. It may be combined with androgen deprivation therapy for higher stage disease. It is also sometimes used for palliation of symptoms of the advanced-stage disease such as pain, bleeding, and obstructive problems.
Androgen Deprivation Therapy (ADT): It is also known as androgen suppression therapy or simply hormonal therapy. This treatment approach is based on the fact that prostate cells grow under the influence of androgens (male sex hormones: testosterone and dihydrotestosterone [DHT]). Androgens are predominately produced by the testicles and a small amount is also produced by the adrenal glands. Depriving the prostate cells of the androgen or by lowering the androgen level in the blood cause their shrinkage or make them grow very slowly. ADT is considered as the primary treatment for locally advanced or metastatic disease. It can also be combined with other treatment modalities such as radiotherapy. Following are some common types of ADT used for the treatment of prostate cancer:
- Orchiectomy: Since the testicles are the chief source of androgens in the body, removing them by surgery reduces the blood androgen level significantly, which leads to shrinkage of prostate cancer in most cases. This is also known as surgical castration.
- Luteinizing hormone-releasing hormone (LHRH) agonists: They are also known as gonadotropin-releasing hormone (GnRH) agonists. These drugs (e.g. Leuprolide, Goserelin, and Triptorelin) decrease the level of androgen in the blood by acting on the pituitary gland, which in turn signals to stop the production of androgen from the testicles. Treatment with these drugs is sometimes referred to as medical or chemical castration.
- LHRH antagonist: Similar to LHRH agonists, these drugs (e.g. Degarelix) decrease the production of androgen from the testicles by acting on the pituitary gland.
- Cytochrome P450 (CYP)17 Inhibitor: LHRH agonists/antagonists stop the testicles to produce androgens, but adrenal glands and some prostate cancer cells can secrete small amounts of androgens which can help in the growth of the prostate cancer. CYP17 inhibitors (e.g. Abiraterone) block the secretion of androgen from the adrenal glands. Treatment with LHRH agonists/antagonists needs to be continued along with CYP17 inhibitor treatment. This treatment approach is generally employed for castration-resistant (unresponsive or resistant to surgical or medical castration) prostate cancers.
- Anti-androgens: Anti-androgens (e.g. Flutamide, Bicalutamide, Nilutamide, etc) are drugs that prevent androgens from producing their effect by blocking the androgen receptors present on prostate cancer cells. This treatment approach is utilized when surgical or medical castration is not working alone (that is for castration-resistant prostate cancers).
- Estrogens: Estrogen is a female sex hormone and it can be used as an alternative to orchiectomy for the treatment of prostate cancer. But due to serious side effects like blood clots and breast enlargement, endogens are not commonly used now.
Surgical or medical castration using ADT may lead to several side effects like erectile dysfunction, a decrease in sexual desire, reduction in the size of testicles, hot flashes, breast enlargement, osteoporosis, anemia, loss of muscle mass, fatigue and depression among others.
Chemotherapy: Chemotherapy means treatment with anti-cancer drugs that kill or decrease the growth of rapidly growing cancer cells. Chemotherapy is generally considered for the treatment of castrate resistant prostate cancer, but may be used upfront in first line in some cases of high burden disease. It may be associated with side effects due to its effect on normal body cells apart from cancerous cells.
Cancer Vaccine: A prostate cancer vaccine (e.g. Sipuleucel-T) may be used for an advanced-stage disease resistant to hormonal therapy. It is prepared by using patient’s white blood cells that are exposed to a prostate cancer protein – prostatic acid phosphatase (PAP). The treated cells are then returned to the patient’s circulatory system where they activate the immune system to act against the prostate cancer cells.
Bone Directed Therapy: Prostate cancer has a high tendency for spread to bones which may lead to various symptoms like pain in bones, fractures, and a significant increase in calcium level in the blood. To avoid these complications or relieve symptoms of bone metastasis, following bone directed therapies are generally employed (along with primary treatment) for prostate cancer:
- Bisphosphonates: Bisphosphonates (e.g. Zoledronic acid) is a class of drug which helps in maintaining bone density in patients who are at high risk of bone damage. Normally, bones are constantly remodeled by two types of bone cells: osteoblasts (they increase bone density) and osteoclasts (they decrease bone density). Bisphosphonates decrease the activity of osteoclasts by inducing apoptosis (natural cell death) in them, thereby help in maintaining bone density and relieve symptoms of bone metastasis. Bisphosphonates may cause side effects such as flu-like symptoms, bone or joint pain, kidney problems, and rarely a serious problem called osteonecrosis of the jaw (ONJ).
- Denosumab: Denosumab is a monoclonal antibody that binds to RANKL and blocks osteoclast maturation, thus reducing bone resorption and helps in maintaining bone density and relieve symptoms of bone metastasis. It can cause side effects like hypocalcemia, osteonecrosis of jaw, etc.
- Radiopharmaceuticals: Various radiopharmaceuticals (e.g. Strontium-89, Samarium-153, and Radium-223) have been developed to treat bone metastasis. Radium-223 is most widely used among them. Due to chemical similarity with calcium, after intravenous administration, Radium-223 is preferentially taken up by bones of the affected areas, where it kills cancer cells by emitting alpha-rays. Due to its specific action against bone metastasis, it is recommended as treatment for patients with prostate cancer and bone metastasis.
It is very important to assess the benefits of each treatment option versus the possible risks and side effects before making a treatment decision. Sometimes patient’s choice and health condition is also important to make a treatment choice.
Following are goals of treating advanced-stage prostate cancer:
- Prolongation of life
- Reduction of symptoms
- Improvement of overall quality of life
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