Prostate Cancer

Overview of Staging

Similarly to other cancers, prostate cancer treatments vary depending the cancer’s stage of progression. After a biopsy is taken of the tumor, the cancer can be staged according to the American Joint Committee on Cancer TMN (tumor, nodes, metastasis) system:

T categories

These are divided into four categories (1-4) and describe the local extent of the tumor.

❖     T1: physician cannot see the tumor through imaging techniques or feel it during examination, but was rather found on accident when conducting other prostate tests.

❖     T2: the tumor shows up in imaging tests and the doctor can feel it, but the tumor is confined to the prostate.

❖     T3: the tumor has begun to spread to the seminal vesicles.

❖     T4: tumor has spread to nearby organs such as the bladder, rectum, or pelvic wall.

N categories

These categories describe the condition of lymph nodes near the cancer.

❖     NX: lymph nodes are not assessed.

❖     N0: nearby lymph nodes not affected.

❖     N1: tumor has spread to nearby lymph nodes.

M categories

❖     M0: cancer has not spread to lymph nodes.

❖     M1: cancer has spread beyond nearby lymph nodes.

Based on TMN scores and other diagnostic tests, the patient’s cancer will be staged from 1-4. From there, a personalized treatment can be planned to combat the cancer.1

In addition, prostate cancer can be castration resistant, which means that the cancer is still dependent on androgen levels, even after removal of the testicles.

Treatments: Best Practices

Androgen Deprivation Therapy (ADT)

This form of hormone therapy works by depriving the male body of the hormones testosterone and dihydrotestosterone (DHT). When these hormones reach the prostate, they promote growth of prostate cancer cells. By preventing this, the cancer should shrink and grow more slowly over time. However, ADT is rarely used as a standalone treatment. It is most effective when used before radiation therapy to shrink to tumor to increase the likelihood of success of the radiation or surgery. ADT can also be a good option if the patient is unable to have surgery, undergo radiation therapy, or if the cancer is reoccurring.There are several types of hormone therapy:

❖     Luteinizing hormone-releasing hormone (LHRH) agonists: these drugs prevent the testicles from receiving signals that trigger testosterone production. This method is just as effective removing the testicles, although its effects are reversible. However, these drugs do cause a “flare” or temporary increase in testosterone production. This can cause cancer cells to increase their activity. LHRH is administered either by direct injection or by implants placed under the skin. Doses can be given every month, or as little as once a year.

❖     LHRH antagonists: also called gonadotropin releasing hormone antagonist do essentially the same thing as the agonist, but does it more quickly and does not cause the flare. Currently, the only FDA approved drug of this type is Firmagon, which is administered monthly by injection.

❖     Anti-androgens: whereas agonists and antagonists are meant to lower testosterone levels, anti-androgens act by preventing the binding of androgens to their respective receptors on the cancer cells. New anti-androgens that block receptors that signal cell division is called Xtandi. Others that are prescribed in varying cases are Casodex, Eulexin and Enzalutamide.

Radical Prostatectomy

This is the main type of surgery used to treat prostate cancers that have not spread (T1 or T2). The surgery involves removing the entire prostate, as well as the seminal vesicles. There are three common approaches to this surgery: retropubic, perineal, and laparoscopic prostatectomy.

The retropubic approach involves an incision below the belly button down to the pubic bone. At this point in the surgery, the surgeon will check nearby lymph nodes to see if the cancer has metastasized. If lymph nodes are affected, the surgery may be stopped since surgery will not be a cure if the cancer has spread. In cases such as this, removing the prostate could cause further complications and a new treatment strategy will be recommended.

The perineal approach involves an incision between the scrotum and the anus. Compared to the retropubic approach, this surgery is easier to recover from and can be just as effective if no lymph nodes need to be removed. However, the perineal approach is used less often because there are many nerves that cannot be saved in this area.

Laparoscopic prostatectomy is done with several small incisions and a camera probe which allows the surgeon see inside the abdomen. It has several advantages such as less pain, less blood loss, and shorter hospital stays. Compared to the radical or open surgeries, this method can be just as effective if done correctly.

All forms of prostatectomy require that a catheter be applied for 1 to 2 weeks to aid in urinating. After the catheter is removed, physical activity should be limited for about 3 to 5 weeks.

Radiation Therapy

There are several options when choosing radiation therapy. External beam radiation therapy (EBRT) is primarily used to treat the initial prostate cancer or if it has spread to other organs, although it is not used as often as new treatments.

Newer techniques, such as 3D conformal radiation therapy accurately maps the tumor. This targeted therapy decreases the likelihood that healthy tissue gets damaged by the radiation. A more advanced form of this treatment is called intensity modulated radiation therapy which is completely computer driven. This makes it very precise and useful in vital areas like the spine.

Cryotherapy

A good option for early stage prostate cancers is cryotherapy. The procedure involves a hollow probe inserted through the tissue between the scrotum and anus. It is guided by ultrasound imaging so that the prostate can be accurately targeted without damaging the surrounding tissue. Once the probe reaches the prostate, cool gases are pumped through the probe which creates balls of ices that destroys the gland. To ensure that the urethra is not damaged, warm saline is circulated through to prevent freezing. This method has several advantages because it is less invasive and recovery is relatively quick. However, its effectiveness is limited only to early stage cancers. More advanced tumors should be treated with radiation or more powerful treatments.

Chemotherapy

If the cancer has spread beyond the gland, chemotherapy should be considered as a treatment option. Chemo drugs are given in cycles of several weeks in order to give the patient’s body the opportunity to recover. It is fairly common to prescribe the chemo drug docetaxel in combination with the steroid prednisone as the first treatment. If this does not meet the patient’s needs, the drug cabazitaxel should be tried next. These two drugs have shown the best results in the past, but there are many other drugs available on the market such as: Jevtana, Novantrone, Emcyt, Adriamycin, Velban, Taxol, Paraplatin, and Navelbine. It is important to note that chemotherapy is not as effective for prostate cancer as it is for other cancers. Chemotherapy does not always result in a cure for the cancer, but when used with hormone therapy or used after surgery, it can certainly quell symptoms.

Bone Directed Treatment

A major goal of prostate cancer treatment is to prevent the spread to the bones. This can be very painful and cause further unwanted complications. When cancer cells contact the bone, cells called osteoclasts which break down bone are overactive. A class of drugs called bisphosphonates can help slow down the progression of the spreading, lower elevated calcium levels, strengthen bones and slow down the activity of osteoclasts. The most common bisphosphonate is Zometa and it is delivered via IV injection. In addition drugs like Xgeva and Prolia do the same thing as Zometa but do so by a different mechanism.

Research Pipeline

Custirsen (OGX-011)

Custirsen is an antisense drug that is used to target the protein clusterin. This protein is overexpressed in cancer cells in response to the introduction of anti-cancer agent, namely chemo drugs. Thus, custirsen would be prescribed in adjunct with chemotherapy. The FDA designated custirsen with the Fast Track Designation for use in prostate cancer. A phase III trial that involves patients with metastatic castration resistant prostate cancer is almost complete. Results of this trial should be released in the last quarter of 2013.

Buparlisib

This drug being developed by Novartis is phase I/II trials for treating prostate cancer. It acts by inhibiting the PI3K-AKT-mTOR signalling pathway. This pathway is important in cell metabolism, proliferation and overall survival. It is known that abnormal activity of this pathway can initiate tumors. Inhibiting this pathway altogether can arrest cell growth and induce cell death. Patients being tested in the trials have advanced tumors in which buparlisib will be used independently and in combination with other drugs.

Prostvac-VF

This vaccine is being developed to treat men with castration resistant prostate cancer. It is currently in phase III trials. Prostvac-VF is composed of two viral vectors: the V vector primes the immune system, while the F vector boosts the immune system. The combination of these vectors works to increase T cell activation. Previous phase II trials involving 300 patients showed very promising results, particularly a minimum of 9 months of prolonged life and up to 3 years of survival. This new phase III trial will involve 1200 patients globally and is still recruiting.

Ipilimumab (Yervoy)

This drug is a monoclonal antibody developed by Bristol-Myers Squibb. It acts by binding to cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptors to block certain ligands and activate cytotoxic T-cells. Although its complete mechanism is still unclear, it is believed that antitumor effects from ipilimumab are due to these augmented T-cell immune responses. Cytotoxic T-lymphocytes are able to recognize and destroy cancer cells. Yervoy is approved to treat melanoma, but phase III trials were conducted on metastatic castration resistant prostate cancer. The trial has concluded, with slightly disappointing results for advanced tumors. Yervoy failed to meet the primary endpoint measurements, however all hope in this drug is not lost. Secondary measurements such as progression free survival and reduction in PSA levels (prostate specific antigen) are significant. Researchers claim that Yervoy should not be ruled out as a treatment for earlier, non-metastatic prostate cancers. Future studies will be conducted with participants with less advanced cancers.

 Centers of Excellence

❖     The Urology Center of Colorado, Denver, Colorado: shows expertise in radiation and hormone therapy

❖     Lakeland Regional Medical Center, Lakeland, Florida: expertise in robotic prostatectomy and other treatments

❖     Wake Forest School of Medicine

❖     Cedars-Sinai Medical Center, Los Angeles, California

❖     Cleveland Clinic, Cleveland, Ohio

❖     Duke University Medical Center, Durham, North Carolina

❖     Johns Hopkins Medical Institutions, Baltimore, Maryland

❖     Loyola University Medical Center, Chicago, Illinois

❖     The Mayo Clinic, Rochester, Minnesota

❖     Memorial Sloan-Kettering Cancer Center, New York, New York

❖     University of California, San Francisco Medical Center, San Francisco, California

❖     University of Iowa Holden Comprehensive Cancer Center, Iowa City, Iowa

❖     University of Kansas Medical Center, Kansas City, Kansas

❖     University of Texas M. D. Anderson Cancer Center, Houston, Taxas

❖     Vanderbilt University Medical Center, Nashville, Tennessee

❖     Washington University Medical Center, St. Louis, Missouri

The last 13 centers were recommended by Medical Economics.

 

 

 

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