Trying New Potential Treatments
You may also want to talk to your doctor about taking part in a clinical trial. These are studies that test treatments to see if theyâre safe and if they work. They might be new drugs or a mix of treatments that haven’t been used together before. You could also be part of the “control” group and not get the new treatment at all. Clinical trials offer you early access to brand new treatments, but itâs also important to remember that they may not work. Youâll want to talk with your doctor to make sure you understand the pros and cons of a research study before you join one. To find clinical trials, ask your doctor or search the National Institutes of Health database at www.clinicaltrials.gov.
At some point, your treatment may stop working. If that happens, you can still get care to ease symptoms like nausea, pain, and tiredness. Even though it may not cure your cancer, the goal is to make you feel better.
American Cancer Society: “Hormone therapy for prostate cancer,” “Preventing and treating prostate cancer spread to bones,” “Vaccine treatment for prostate cancer,” “What is metastatic cancer?” “When Cancer Doesn’t Go Away,” âUnderstanding Advanced and Metastatic Cancer,â âWhatâs New in Prostate Cancer Research?â
Prostate Cancer UK: âWhat is locally advanced prostate cancer?â
ClinicalTrials.gov: “Learn About Clinical Studies.”
National Cancer Institute: “Cancer Vaccines.”
Causes Of Advanced Prostate Cancer
Prostate cancer is one of the most common cancers in the UK. It is more common over the age of 65. Prostate cancer can happen in younger people, but it is uncommon in people aged under 50.
If you are a trans woman or are non-binary or assigned male at birth, you also need to be aware of prostate cancer. Advanced prostate cancer may affect trans women, but there is not enough evidence to know how common this is.
Prostate cancer UK have detailed information about trans women and prostate cancer.
Doctors do not know the exact causes of prostate cancer. But there are risk factors of prostate cancer that can increase the chance of developing it. Having one or more risk factors does not mean you will get prostate cancer.
You may be diagnosed with advanced prostate cancer:
- after previous treatment for early or locally advanced prostate cancer possibly many years ago
- after being diagnosed with cancer in the prostate, if further tests show the cancer is advanced
- after tests to check symptoms of bone pain, with no previous diagnosis of prostate cancer.
The most common places for prostate cancer to spread to is to the bones and lymph nodes outside the pelvis.
What Kinds Of Prostate Cancer Does Nubeqa Treat
Nubeqa is the latest oral medication approved by the FDA to be used in the treatment of these two kinds of advanced prostate cancer:
- Metastatic Hormone-Sensitive Prostate Cancer . Up to one third of patients with prostate cancer eventually develop mHSPC. This happens when the cancer spreads beyond the prostate to other areas of the body. The condition can be treated with hormone therapy which means that male sex hormones, including testosterone, can be blocked or stopped to slow the cancer growth. However, down the road, many patients end up developing resistance to the hormone treatment resulting in a recurrence of cancer. Anywhere from 40 percent of patients go into a resistant state, Dr. Shore says.
- Non-metastatic Castration Resistant Prostate Cancer . This is a kind of advanced prostate cancer that no longer responds to hormone treatment. Although it shows signs of growth, such as a rising PSA level, cancer cells are only found in the prostate. The cancer has not spread.
Dr. David Wise, a medical oncologist at NYU Perlmutter Cancer Center, explains how treatment for advanced prostate cancer has improved in recent years.
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A Biopsy Is Done To Diagnose Prostate Cancer And Find Out The Grade Of The Cancer
A transrectal biopsy is used to diagnose prostate cancer. A transrectal biopsy is the removal of tissue from the prostate by inserting a thin needle through the rectum and into the prostate. This procedure may be done using transrectal ultrasound or transrectal MRI to help guide where samples of tissue are taken from. A pathologist views the tissue under a microscope to look for cancer cells.
Sometimes a biopsy is done using a sample of tissue that was removed during a transurethral resection of the prostate to treat benign prostatic hyperplasia.
If cancer is found, the pathologist will give the cancer a grade. The grade of the cancer describes how abnormal the cancer cells look under a microscope and how quickly the cancer is likely to grow and spread. The grade of the cancer is called the Gleason score.
To give the cancer a grade, the pathologist checks the prostate tissue samples to see how much the tumor tissue is like the normal prostate tissue and to find the two main cell patterns. The primary pattern describes the most common tissue pattern, and the secondary pattern describes the next most common pattern. Each pattern is given a grade from 3 to 5, with grade 3 looking the most like normal prostate tissue and grade 5 looking the most abnormal. The two grades are then added to get a Gleason score.
Role In Prostate Cancer Treatment
Anti-androgens are typically reserved for advanced stages of prostate cancer, such as when cancer has spread to other parts of the body.
Anti-androgens are sometimes prescribed in addition to orchiectomy or luteinizing hormone-releasing hormone agonists when these therapies arent working alone. They may also be prescribed with these treatments as first-line therapy.
Prostate cancer that doesnt respond to other types of androgen deprivation therapy is known as castration-resistant prostate cancer.
The American Urology Association also stated in 2018 that second-generation anti-androgens can be used earlier in prostate cancer along with other pharmaceutical hormone therapies for people who are likely to have their cancer spread to other parts of the body.
In some cases, prostate cancer cells can become resistant to first-generation anti-androgens. They may develop mutations that prevent binding to the androgen receptor or that allow the receptor to become activated after binding to the anti-androgen itself.
If this happens, you may still respond to second-generation anti-androgens, and your oncologist may recommend a change of treatment.
Anti-androgens are associated with a variety of possible side effects, including:
- breast tenderness or tissue growth
- reduced sex drive
- erectile dysfunction
In rare cases, particularly with the use of flutamide, liver injury can occur. Talk with your doctor about monitoring your liver values during treatment.
What Questions Should I Ask My Healthcare Provider
If you have prostate cancer, you may want to ask your healthcare provider:
- Why did I get prostate cancer?
- What is my Gleason score? What is my Grade Group? What do these numbers mean for me?
- Has the cancer spread outside of the prostate gland?
- What is the best treatment for the stage of prostate cancer I have?
- If I choose active surveillance, what can I expect? What signs of cancer should I look out for?
- What are the treatment risks and side effects?
- Is my family at risk for developing prostate cancer? If so, should we get genetic tests?
- Am I at risk for other types of cancer?
- What type of follow-up care do I need after treatment?
- Should I look out for signs of complications?
A note from Cleveland Clinic
Prostate cancer is a common cancer that affects males. Most prostate cancers grow slowly and remain in the prostate gland. For a small number, the disease can be aggressive and spread quickly to other parts of the body. Men with slow-growing prostate cancers may choose active surveillance. With this approach, you can postpone, and sometimes completely forego, treatments. Your healthcare provider can discuss the best treatment option for you based on your Gleason score and Group Grade.
Management Of Metastatic Castration
Until 2004, progression on androgen deprivation therapy for metastatic castration-resistant prostate cancer was treated with the addition of secondary hormonal manipulation, including antiandrogens such as bicalutamide and nilutamide , ketoconazole , or corticosteroids . Mitoxantrone, the first cytotoxic chemotherapy approved for mCRPC by the US Food and Drug Administration , was approved on the basis of improved palliative responses in pain-related measures despite no survival benefit .
Docetaxel, a microtubule inhibitor and the first systemic therapy to demonstrate survival benefit in mCRPC, was studied in two prospective phase III trials . The TAX 327 trial randomized 1,006 patients to docetaxel plus prednisone every three weeks, weekly docetaxel, or mitoxantrone every three weeks. The Southwest Oncology Group 99â16 trial randomized 675 patients to docetaxel plus estramustine or mitoxantrone. In both studies, docetaxel administered every three weeks demonstrated clear survival benefit, with a median overall survival gain of 1.9 to 2.4 months, establishing docetaxel as the new standard of care for mCRPC in 2004. These trials also changed the understanding of CRPC and consequently influenced a generation of prospective clinical trials comparing chemotherapy-naive with postdocetaxel outcomes.
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Side Effects Of Chemotherapy
- Digestive issues such as nausea, vomiting and diarrhea
While on chemotherapy, patients are also susceptible to infections because their white blood cell counts are lower. Other common side effects include bruising or bleeding due to fewer blood platelets and fatigue due to the lowered red blood cell count.
Its also possible to experience a severe allergic reaction to some of the drugs used to treat prostate cancer, especially Taxotere® and Jevtana® . The patients care team may recommend medicines before each session to help prevent a reaction.
The prostate chemotherapy drug mitoxantrone may cause leukemia later in life, but this is rare. The prostate chemotherapy drug Emcyt® may increase the risk for blood clots.
During chemotherapy, doctors may also offer supportive care services to help ease side effects. For example, naturopathic providers may suggest supplements to reduce nausea. Also, a mind-body therapist may recommend techniques to help the patient relax and feel less anxious during prostate cancer chemotherapy treatments.
Radiation Therapy In Metastatic Crpc
Approximately 90% of advanced PCa patients will develop bone metastases. Radiation therapy is an important therapeutic option for of bone disease. Patients with isolated, painful bone lesions may be treated with palliative external beam radiation. Additionally, oligometastatic disease may be treated to slow progression. Systemically administered, bone targeted radiopharmaceuticals can be used for control of bone predominant disease. Radium-223 is an alpha particle emitting agent approved for the treatment of mCRPC patients with symptomatic bone lesions, without visceral disease. Patients in the ALSYMPCA trial receiving radium-223 had an improvement in OS as well as significant improvements in skeletal- and pain-related outcomes.20 Treatment with radium-223 alone has been shown effective in comparison to placebo however, there are several ongoing studies investigating combinations with other approved agents in mCRPC.
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Biggest Breakthroughs In Advanced Prostate Cancer Treatment
Prostate cancer is most often diagnosed at an early and highly treatable stagebut if youre one of the men with advanced-stage prostate cancer at diagnosis, youre in a club whose numbers have risen in the last decade, according to the Centers for Disease Control and Prevention . Thankfully, advancements in prostate cancer research have led to promising improvements in treatment possibilities for this club. We spoke to the experts to learn more about breakthroughs that are changing the treatment game in prostate cancer.
Does Overdiagnosis Lead To Overtreatment Of Older Men
The widespread use of PSA screening has led to an increase in the diagnosis and treatment of early localized prostate cancer. Data from the US Cancer of the Prostate Strategic Urological Research Endeavor database suggest a significant decrease in risk in the last 2 decades in the United States, with more patients being identified with low-risk disease at diagnosis, but the role of active treatment of low- and intermediate-risk disease in elderly men remains controversial.
The median time from diagnosis to death from prostate cancer for men with nonpalpable disease is approximately 17 years., Considering that the US male life expectancy at the age of 65 years is 16 years, aggressive therapy will hardly extend life expectancy of older men with no palpable prostate cancer at the time of diagnosis. Twenty to 30% of prostate cancers detected by PSA screening programs show Gleason scores of 6 or lower and, thus, are not poorly differentiated and have volumes smaller than 0.5 cm3.
Histologic evaluation of radical prostatectomy specimens demonstrated that about 20% to 30% of cancers are small volume, show low Gleason scores, and are consequently clinically harmless., Many of these cancers pose little threat to life, especially for older men. Has PSA screening resulted in prostate cancer overdiagnosis?
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Active Surveillance And Watchful Waiting
If prostate cancer is in an early stage, is growing slowly, and treating the cancer would cause more problems than the disease itself, a doctor may recommend active surveillance or watchful waiting.
Active surveillance. Prostate cancer treatments may seriously affect a person’s quality of life. These treatments can cause side effects, such as erectile dysfunction, which is when someone is unable to get and maintain an erection, and incontinence, which is when a person cannot control their urine flow or bowel function. In addition, many prostate cancers grow slowly and cause no symptoms or problems. For this reason, many people may consider delaying cancer treatment rather than starting treatment right away. This is called active surveillance. During active surveillance, the cancer is closely monitored for signs that it is worsening. If the cancer is found to be worsening, treatment will begin.
ASCO encourages the following testing schedule for active surveillance:
A PSA test every 3 to 6 months
A DRE at least once every year
Another prostate biopsy within 6 to 12 months, then a biopsy at least every 2 to 5 years
Treatment should begin if the results of the tests done during active surveillance show signs of the cancer becoming more aggressive or spreading, if the cancer causes pain, or if the cancer blocks the urinary tract.
Combination Radiation And Endocrine Therapy
Sometimes, patients receive hormone therapy in combination with external beam radiation therapy for the treatment of prostate cancer. This treatment uses a high-energy X-ray machine to direct radiation to the prostate tumor. For patients with intermediate or high risk prostate cancer, studies show this combination is more effective at slowing the disease than endocrine therapy or radiation therapy alone.
Radiation can also come in the form of a monthly intravenous drug called Xofigo. Xofigo is approved for use in men who have advanced prostate cancer that has spread only to the bones. Candidates should have also received therapy designed to lower testosterone. The drug works by binding to minerals within bones to deliver radiation directly to bone tumors. A study of 809 men showed that those taking Xofigo lived an average of 3 months longer than those taking a placebo.
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Noncastrate Prostate Cancerthe New Frontier
Despite advances in the therapeutic landscape, most mCRPC patients will eventually experience disease progression and succumb to prostate cancer. Noncastrate disease states, shown to harbor lower genetic heterogeneity and complexity , have attracted interest because of the potential opportunity to use existing therapies to improve clinical outcomes.
Locally Advanced Prostate Cancer
For all types of cancer, the term âlocally advancedâ means the cancer has spread beyond the body part where it started but only to nearby tissues, organs, or lymph nodes. Your prostate is a walnut-sized gland that is below your bladder. A locally advanced prostate cancer means that the cancer cells have broken out of your prostate or moved to just outside of it.
Your doctor may refer to locally advanced prostate cancer as stage T3 or T4 prostate cancer. âAdvanced cancerâ usually refers to cancer that canât be cured. But some locally advanced prostate cancers are curable.
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Other Risk Factors Include:
- Race and Ethnicity. The CDC reports that African-American men have the highest rate of prostate cancer, followed by white, Hispanic, American Indian/Alaska Native and Asian/Pacific Islander men. According to the American Cancer Society, African -American men are twice as likely to die from prostate cancer as white men.
- Genetics/Heredity. Prostate cancer seems to run in families, which suggests that in some cases, there may be an inherited or genetic factor, Dr. Shore says. For instance, having a father or brother with the disease more than doubles a mans risk of developing it.
- Geography. Prostate cancer is most common in North America, northwestern Europe, Australia, and on Caribbean islands. Its less common in Asia, Africa, Central and South America. Why? Well, that still needs to be determined. The fact that theres more frequent screening for the disease in some developed countries may account for at least a portion of the statistical risk.
- More possibilities. Other contributors include smoking, obesity, diet and chemical exposure. For example, firefighters who are frequently exposed to combustion byproducts, as well as farmers exposed to agricultural pesticides have higher rates. Further research is needed to confirm these connections.
Immunotherapy In Metastatic Crpc
Immunotherapy aims to augment the immune response against progressing cancers. Sipuleucel-T is an FDA-approved autologous dendritic cell vaccine that acts by enhancing T-cell responses. Treatment with sipuleucel-T produced a significant improvement in OS compared with a similar leukocyte product placebo however, there was no significant improvement in PFS, and only 2.6% of patients in the sipuleucel-T arm had PSA declines of 50%.21 Prostvac is a PSA/vaccinia-based vaccine currently being evaluated, with impressive improvements in OS in phase II trials. Unfortunately, the registration Phase III trial was recently reported to be negative. However, there are several ongoing trials of Prostvac in combination with checkpoint inhibitors.
Ipilimumab has been evaluated in two recently reported Phase III studies in mCRPC patients. While there was minimal improvement in OS with borderline significance in the first reported trial in post-chemotherapy patients receiving radiation,22 a second trial in pre-chemotherapy trials was also unfortunately negative.23 Combination studies with ipilimumab, as well as other checkpoint inhibitors are actively being evaluated in the mCRPC setting.
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