At present, there is no cure for advanced prostate cancer, but treatment can control the spread of the tumor and associated symptoms. These treatments often have side effects, and for some patients, especially those of advanced age, the risk of side effects may outweigh the benefits of treatment and therefore may choose to forgo treatment.
While there is no cure for advanced prostate cancer, scientists have been exploring new and more effective treatment options that would have fewer side effects, more effective control of the disease, and longer survival. Here are a few effective options for treating advanced prostate cancer!
Endocrine therapy is one of the most common therapies that many doctors use to save the lives of patients with advanced prostate cancer.
Benefits and drawbacks
Androgens, especially testosterone, promote the growth of prostate cancer. By reducing the synthesis of testosterone or decreasing its activity, the growth of advanced prostate cancer can be slowed. Endocrine therapy, also called androgen suppression therapy, is the mainstay of treatment for advanced prostate cancer as well as a first-line treatment option for metastatic prostate cancer.
For most patients, endocrine therapy temporarily relieves the symptoms of advanced prostate cancer, shrinks tumors, and reduces levels of prostate-specific antigen (PSA), a substance secreted by the prostate gland, which may indicate prostate cancer when PSA levels are abnormally high.
However, endocrine therapy can also have side effects, the more serious of which include loss of libido, erectile dysfunction, osteoporosis, and heart disease.
After a period of treatment, most patients with advanced prostate cancer eventually lose their response to endocrine therapy, which doctors refer to as “destructive prostate cancer.
Selecting drugs over surgery
Both drugs and orchiectomy are effective in lowering androgen levels in the body. However, most patients choose drug therapy over surgery. The four hormone-related drugs approved for the treatment of advanced prostate cancer include luteinizing hormone-releasing hormone (LHRH) analogs, LHRH antagonists, anti-androgens, and androgen biosynthesis inhibitors.
Luteinizing hormone-releasing hormone (LHRH) analogs
Most patients receiving endocrine therapy choose LHRH analogs, which reduce testosterone synthesis by inhibiting pituitary hormone release.
However, there is a temporary increase in testosterone synthesis and tumor growth in patients until testosterone levels show a decrease. This is due to a short-term compensatory increase in LHRH release from the pituitary gland after drug administration, which stimulates testosterone synthesis, a phenomenon known as tumor flare.
Tumor flare can increase symptoms that some patients never had before receiving treatment, and doctors may prescribe anti-androgens to counteract these symptoms or add LHRH analogs after the patient has been on anti-androgens for a while.
LHRH analogs are given by injection or subcutaneous implant. Common LHRH analogs are leuprolide, histrelin, treprostinil, and goserelin, which cause side effects similar to those caused by orchiectomy.
In addition, these medications may increase the risk of diabetes, heart disease, osteoporosis, and stroke. Before starting these drugs, patients should inform their doctor if they have diabetes, heart disease, stroke, myocardial infarction, high blood pressure, high blood cholesterol, or if they smoke.
LHRH antagonists
These drugs are approved to treat prostate cancer. LHRH antagonists lower testosterone levels faster than LHRH analogs, and they do not cause tumor scintigraphy (a temporary increase in testosterone levels) like LHRH analogs do.
Degarelix, an LHRH antagonist used to treat advanced prostate cancer, has been shown to slow the progression of the disease, but further trials are needed to clarify its long-term efficacy. It is well tolerated, with common side effects of causing local injection site reactions and elevated levels of certain liver enzymes.
Anti-androgen drugs
Anti-androgen drugs work by blocking the action of testosterone in the body. Doctors sometimes use anti-androgens in addition to orchiectomy or LHRH analogs because other forms of endocrine therapy only eliminate about 90% of the testosterone in the body, while anti-androgens may block the remaining 10% of the testosterone in the body.
When anti-androgens are used in combination with another form of endocrine therapy, it is called combined androgen blockade (CAB) or total androgen ablation. Anti-androgen drugs can also be used to combat the phenomenon of tumor scintigraphy, and some physicians will prescribe antiandrogen drugs alone without concomitant orchiectomy or LHRH analogs.
Available antiandrogen drugs include bicalutamide, enzalutamide, flutamide, and nilumet, which are primarily administered in oral form. When anti-androgens are used as part of combination therapy, the main side effect is diarrhea, and less frequent side effects include nausea, liver disease, and fatigue; when used alone, anti-androgens have the potential to cause loss of libido and erectile dysfunction.
Androgen biosynthesis inhibitors
Androgen biosynthesis inhibitors inhibit androgen synthesis in testicular, adrenal, and prostate cancer cells by inhibiting the activity of CYP17, a key enzyme in the androgen synthesis pathway, and thereby inhibiting prostate cancer progression.
The currently approved androgen synthesis inhibitor is abiraterone acetate, which is used clinically primarily in combination with prednisone for the treatment of patients with desmoplastic-resistant prostate cancer. Recent findings support that initial endocrine therapy with abiraterone acetate may achieve better outcomes in patients with metastatic prostate cancer who have not been previously treated with endocrine therapy.
The major adverse effects of abiraterone acetate include hypertension, hypokalemia, fluid retention, hepatic impairment, and loss of appetite.
Radiotherapy combined with endocrine therapy
Sometimes doctors treat prostate cancer with a combination of endocrine therapy and external radiation therapy, which uses a high-energy x-ray machine to direct radiation to the prostate tumor. For patients with intermediate or high-risk prostate cancer, this combination therapy is more effective in slowing disease progression than endocrine therapy or radiation therapy alone.
Radium 223 dichloride is also approved in the United States for the treatment of advanced prostate cancer that has spread to the bone, while patients are also treated with endocrine therapy. Radium 223 dichloride binds to bone minerals and emits radiation to kill prostate cancer cells in bone metastases. In a study that included 809 patients with prostate cancer, the median survival was 3.6 months longer with radium-223 dichloride than with placebo.
Two other similar radiotherapy drugs are strontium-89 (strontium-89) and samarium-153 (samarium-153).
Second-line endocrine therapy
When PSA levels continue to rise after endocrine therapy, which indicates that the original endocrine therapy is no longer effective in controlling prostate cancer, the doctor may decide to switch to another endocrine therapy, which is called “second-line endocrine therapy.
For example, if a patient has had an orchiectomy, they may be advised to start an anti-androgen drug. If the patient has been receiving a combination of an antiandrogen and an LHRH analogue, then the doctor may take them off the antiandrogen, which is called “antiandrogen withdrawal. Another option is to change the type of endocrine therapy drug, but the patient must remain on the LHRH drug to prevent testosterone levels from rebounding, which can stimulate prostate cancer cell growth.
Ketoconazole is an antifungal agent that inhibits testosterone synthesis in the adrenal glands and testes when used at high doses. When administered as second-line therapy, 20% to 40% of patients experience significant side effects, and the dose range is 200 to 400 mg three times a day. This drug must be used in combination with hydrocortisone to prevent adrenal insufficiency.
Also, low-dose estrogenic drugs (eg, estradiol, megestrol, etc.) are an option for second-line endocrine therapy.
Chemotherapy
For patients who have failed endocrine therapy, the chemotherapy drug docetaxel combined with prednisone is the standard chemotherapy regimen, usually given intravenously. Docetaxel works by stopping cancer cells from dividing and growing, and has similar side effects to most chemotherapy drugs, including nausea, hair loss, and bone marrow suppression (decreased or stopped blood cell formation), and may also cause neuropathy (tingling, numbness, and pain in the fingers or toes from nerve damage) and fluid retention.
Docetaxel combined with prednisone is the first chemotherapy regimen shown to help prolong survival in patients with advanced prostate cancer. Patients in the docetaxel-combined prednisone treatment group had an average survival extension of about 2.5 months compared with mitoxantrone combined with prednisone. Docetaxel was most effective when given once every 3 weeks compared with weekly dosing.
Carbataxel is another chemotherapy drug that can be used in combination with prednisone to treat prostate cancer. If a patient with advanced prostate cancer develops cancer progression during or after treatment with docetaxel, consider switching to cabazitaxel.
The safety and effectiveness of cabazitaxel was based primarily on a study of 755 patients, all of whom were previously treated with docetaxel. The study showed that patients treated with cabazitaxel had a median overall survival of 15.1 months, compared with a median overall survival of 12.7 months for patients receiving the mitoxantrone regimen.
Side effects of cabazitaxel treatment include significant reduction in white blood cells (neutropenia), anemia, low platelet levels (thrombocytopenia), diarrhea, fatigue, nausea, vomiting, constipation, weakness, and renal failure.
Prostate cancer vaccine
Sipuleucel-T is a “vaccine” for advanced prostate cancer that extends the survival of patients.
Sipuleucel-T is not a vaccine as we usually know it, it is an immunotherapy where doctors take immune cells from patients, genetically engineer them to fight prostate cancer, and then inject them back into the patient.
Currently, Sipuleucel-T is only approved to treat patients with metastatic debulking-resistant prostate cancer who have few or no symptoms, whose cancer has spread beyond the prostate, and for whom first-line endocrine therapy has not worked. Currently, Sipuleucel-T is not available in China or in any European country.
The most common side effect of Sipuleucel-T is chills, which occur in more than half of patients, and other common side effects include fatigue, fever, back pain, and nausea. sipuleucel-T is generally very safe, although some clinical trials suggest that this therapy may slightly increase the risk of stroke.
Surgery
For some patients with advanced or recurrent prostate cancer, surgeons may perform a “salvage” prostatectomy to remove the entire prostate. A nerve-preserving prostatectomy is not usually performed, and the pelvic lymph nodes are also removed.
If the cancer has not spread beyond the prostate, cryosurgery (also called cryotherapy) may be used to prevent the prostate cancer from coming back.
To lower the level of testosterone in the body, doctors sometimes recommend removing the testicles (orchiectomy). After surgery, patients may choose to wear a prosthesis that resembles the shape of a testicle.
Doctors may also perform a transurethral resection of the prostate (TURP) to relieve the blockage caused by the prostate tumor so that urine can drain normally. This is a palliative measure that improves patient comfort, but does not cure prostate cancer.
New therapies
Scientists are working on several new approaches to treating advanced prostate cancer. Among them, antibodies against programmed death protein-1 (PD-1) and programmed death protein ligand-1 (PD-L1), known as immune checkpoint inhibitors, show good promise.
In tumor patients, PD-L1 on the surface of tumor cells can bind to PD-1 on the surface of immune cells, thus evading immune killing. Antibodies to PD-1 and PD-L1 block this pathway to evade immune killing, allowing immune cells in the patient to clear the tumor cells. This therapy has been approved in a variety of solid tumors, such as kidney cancer, bladder cancer, and melanoma.
In prostate cancer this therapy is not yet approved, but there are clinical trials currently underway.