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.
T1a-2 N0 M0, PSA<10, GG=1 (Very Low to Low-Risk Disease)
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.
T2b-2c N0 M0 PSA<20 GG=1 TO T1-2 N0 M0 PSA<20 GG=3-4
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.
T1-2 N0 M0 PSA>/=20 GG=1-4 TO Any T N0 M0 Any PSA GG=5
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.
Any T N1 M0 Any PSA Any GG TO 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.
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.
Now first let’s look at the NATURAL HISTORY of prostate cancer.
This is the prostate cancer natural history. As you can see in the figure it progresses very slowly and the patient may survive for years after diagnosis.
The first peak correlates with localized disease and is treated with local therapy in most of the cases. We will discuss this in detail later.
The second peak correlates with recurrence after local therapy or metastatic disease. It is treated with local or systemic therapy.
The third peak correlates with the castrate-resistant prostate cancer, that is the disease which has progressed on hormonal therapy. It is usually treated with chemotherapy but other agents may also be used.
Prostate Cancer Observation VS Active Surveillance
First, we will discuss what is the difference between observation and active surveillance.
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.
Surgery for prostate cancer is called as radical prostatectomy, in which prostate is removed along with surrounding structures.
The next treatment option is radiotherapy, which can be given as EBRT, IMRT, and brachytherapy. The decision regarding this is taken by the radiation oncologist.
Androgen Deprivation Therapy for Prostate Cancer:
The next treatment modality is androgen deprivation therapy. For this, we first have to understand the hormonal axis causing the testosterone release.
The pituitary gland releases LH and FSH, which directly acts on the testis to release testosterone.
ACTH released from the pituitary gland acts on the adrenal gland to release DHEA, which subsequently gets converted into testosterone.
The testosterone released from testis and adrenal gland enters the prostate cell and gets converted into DHT which causes the growth and survival of prostate cancer cells.
We can block this pathway, to reduce the action of testosterone on prostate cancer cells. GnRH agonists or antagonists prevent the release of LH, FSH, and ACTH from the pituitary gland.
Then come the cytochrome 17P inhibitors that prevent the release of testosterone from the testis and adrenal gland.
And finally, there are androgen receptor blockers that prevent the binding of testosterone to prostate cancer cells, thereby preventing its action.
Another method for androgen deprivation is surgical castration in which both testes are removed. Unlike medical construction, it is a one-time procedure.
Castrate Resistant Prostate Cancer Treatment:
CancerBro will explain treatment for castrate-resistant prostate cancer. Watch the video to know how the disease is treated in most cases.
CancerBro, I was started on GnRH analog, but my disease progressed on that. What are the treatment options in such cases?
After some years of starting androgen deprivation therapy, PSA may start rising, or there may be a disease progression on scans. This state is called as castrate-resistant prostate cancer.
If the patient has localized CRPC, then the treatment options are the observation or androgen deprivation therapy with a different agent that used previously.
And for metastatic CRPC, the treatment options are androgen deprivation therapy, chemotherapy, cancer vaccine or bone-directed therapy.
CRPC is the disease which has progressed on GnRH analogs, so non-GnRH analogs are used for the treatment, such as androgen receptor blockers or 17 hydroxylase inhibitors.
Recurrent Prostate Cancer Treatment:
The second peak correlates with recurrence after local therapy or metastatic disease. We will discuss it one by one.
Recurrence after surgery may be in the form of PSA persistence, that is a failure to fall to normal, or PSA recurrence, that is, rising after becoming undetectable.
And recurrence after radiation therapy may be in the form of rise in PSA or positive DRE.
For localized recurrence, the treatment options are observation, surgery if initially treated with radiotherapy, radiotherapy if initially treated with surgery and androgen deprivation therapy.
And for metastatic recurrence, androgen deprivation therapy is the mainstay of treatment.
The patients who present directly with metastatic disease are treated directly with hormonal therapy and chemotherapy may be added in some patients who present with high volume disease.
When we use androgen deprivation therapy for the first time for localized, metastatic or recurrence after local therapy, it may be in form of medical or surgical castration.
GnRH agonists or antagonists are used for medical castration, and for surgical castration, both the testes are removed, called as bilateral orchiectomy.