Latest Treatment For Metastatic Prostate Cancer

A New Treatment For Advanced Prostate Cancer Improves Survival In Phase 3 Clinical Trial

• By Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases

Radiation therapy is getting more precise, enabled by technologies that make it easier to kill tumors while sparing their surrounding tissues. Some newer therapies are even given intravenously instead of by machines, and they deliver radiation particles directly to the cancer cell itself. One of these new therapies a sort of smart bomb targeted at malignant cells is now generating promising data for men with the most aggressive prostate cancer.

In early June, investigators reported results from a phase 3 clinical trial showing that among men who received the experimental treatment, there was nearly a 40% reduction in deaths over the course of the study, compared to men who did not.

The treatment is called lutetium-177-PSMA-617, or LuPSMA, and it has two components: a compound that targets a cancer cell protein called prostate-specific membrane antigen, or PSMA, and a radioactive particle that destroys the cells. Healthy prostate cells don’t contain PSMA, or do at very low levels. And some men with prostate cancer have more of the protein than others. Doctors can detect the protein using a specialized imaging scan.

Results after 21 months showed that cancer progression was delayed for longer among the LuPSMA-treated men: 8.7 months on average versus 3.4 months among the controls. The treatment was also associated with better overall survival: 15.3 months versus 11.3 months.

How Is Prostate Cancer Diagnosed

If your doctor suspects that you might have prostate cancer, they may order one or more of the following tests:

• Digital rectal exam . Your doctor inserts a lubricated finger into your rectum to feel for hard areas or bumps on your prostate gland that might be cancer.
• Prostate-specific antigen blood test. A healthcare professional draws a sample of blood to measure your level of PSA, a protein produced in your prostate gland. High PSA levels may be sign of prostate cancer.
• Prostate biopsy. A urologist uses a small needle to collect tissue samples from your prostate. These samples are examined under a microscope for cancer cells.
• Imaging test. An MRI or transrectal ultrasound may be performed before, during, or after a biopsy to help locate abnormal tissue in the prostate.

The results of these tests can help your doctor not only diagnose prostate cancer but also assess your risk of metastatic disease.

If your doctor suspects that you have metastatic prostate cancer, theyll order imaging tests to check for tumors in your lymph nodes, other organs, and bones. Metastatic tumors are also known as metastases.

Doctors have conventionally ordered a combination of imaging tests to check for metastatic prostate cancer. These tests typically include:

• a CT or MRI scan, to check for metastases in your lymph nodes and other organs
• a bone scan, to check for metastases in your bones

In other words, the PSMA PET was 27 percent more accurate than the more conventional testing approach.

Biomarkers For Treatment Selection

Clinical data report that RB1 loss is associated with worse progression-free survival in patients with mCRPC treated with enzalutamide . In addition, the recent comprehensive analysis of 429 patients with mCRPC has identified that RB1 alteration was significantly associated with poor survival, and alterations in RB1 and TP53 were associated with shorter time on treatment with abiraterone or enzalutamide . Androgen-receptor amplifications and mutations are mostly the result of hormonal treatment , but they can also occur in some castration-naïve patients . The AR alterations confer resistance to ADT, and are associated with a worse prognosis, therefore these patients could be candidates to treatment intensification. The circulating tumor cells and the AR splice variant 7 have been proposed as prognostic and predictive biomarkers in patients with mCRPC treated with abiraterone acetate and enzalutamide . However, the prevalence of AR-V7 in untreated mCRPC, and, consequently, in mHSPC, is low . Finally, the role of PSA kinetics, which represent an important criterium for treatment selection in the context of non-metastatic castration-resistant prostate cancer , remains largely unaddressed in the setting of mHSPC.

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New Treatment For Metastatic Prostate Cancer

Date:

Norris Cotton Cancer CenterDartmouth-Hitchcock Medical Center

Summary:

An American hospital has treated three men with a recently FDA-approved treatment for prostate cancer, which offers new options for men whose cancer has spread to their bones. The treatments trade name is Xofigo . It is an alpha particle-emitting radioactive therapeutic agent with an anti-tumor effect.

Dartmouth-Hitchcock Norris Cotton Cancer Center has treated three men with a recently FDA-approved treatment, which offers new options for men whose prostate cancer has spread to their bones. The treatment’s trade name is Xofigo® . It is an alpha particle-emitting radioactive therapeutic agent with an anti-tumor effect.

Treatment entails an injection each week, up to six injections if needed. “When compared with the best existing standard of care, research shows that patients receiving radium-223 injections live longer,” said Thomas C. Sroka, MD, PhD, radiation oncologist, Norris Cotton Cancer Center. “It is also very tolerable,” he said, “with few side effects.”

Xofigo was approved by FDA in May of 2013 and is the first agent of its kind. Clinical trials of the drug showed an improvement of overall survival time from 11.3 months to 14.9 months versus placebo. The most common side effects are nausea, diarrhea, vomiting, and peripheral edema.

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Physical Emotional And Social Effects Of Cancer

Cancer and its treatment cause physical symptoms and side effects, as well as emotional, social, and financial effects. Managing all of these effects is called palliative care or supportive care. It is an important part of your care that is included along with treatments intended to slow, stop, or eliminate the cancer.

Palliative care focuses on improving how you feel during treatment by managing symptoms and supporting patients and their families with other, non-medical needs. Any person, regardless of age or type and stage of cancer, may receive this type of care. And it often works best when it is started right after a cancer diagnosis. People who receive palliative care along with treatment for the cancer often have less severe symptoms, better quality of life, and report that they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies. You may also receive palliative treatments similar to those meant to get rid of the cancer, such as chemotherapy, surgery, or radiation therapy.

Before treatment begins, talk with your doctor about the goals of each treatment in the treatment plan. You should also talk about the possible side effects of the specific treatment plan and palliative care options.

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How Psma Testing Could Improve Prostate Cancer Treatments And Outcomes

The recommended treatment plan for prostate cancer varies depending on several factors, including whether the cancer has spread or recurred. Accurate staging is essential for determining the best treatment approach.

Improved staging at the time of prostate cancer diagnosis or suspected prostate cancer recurrence will ensure that you receive the proper treatment and are not under- or over-treated, Feuerstein explained.

If you have prostate cancer that hasnt yet spread, your doctor may recommend surgery to remove your prostate gland, radiation therapy to kill cancer cells, or a combination of both. If the cancer is slow growing, your doctor may counsel you on the options, such as waiting to start treatment.

If you have metastatic prostate cancer, your doctor will likely prescribe radiation or hormone therapy or both rather than surgery. Hormone therapy lowers levels of the hormone androgen, which slows the growth of prostate cancer.

Your doctor may also prescribe chemotherapy, medications, or other treatments to manage more advanced cancer.

PSMA PET scans may help people with metastatic prostate cancer get earlier and more accurate diagnoses. This may help them avoid unnecessary surgery and begin hormone therapy earlier. Although more research is needed, this might help improve their survival, quality of life, or both.

Staging Of Prostate Cancer

Doctors will use the results of your prostate examination, biopsy and scans to identify the “stage” of your prostate cancer .

The stage of the cancer will determine which types of treatments will be necessary.

If prostate cancer is diagnosed at an early stage, the chances of survival are generally good.

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Treatment For Advanced Cancer

Stage IV prostate cancer is cancer that has spread or metastisized. Cancer metastases results from a primary prostate cancer tumor that has spread to other parts of the body such as the brain, lungs and liver via varying routes including circulatory, lymphatic system, or skeletal structure. Bone metastases causes severe pain and is characterized by a dull, constant ache with periodic spikes of pain. Prostate cancer frequently spreads to the bones. Watch our expert medical oncologist, Alicia Morgans, discuss treatment options for advanced prostate cancer.

Traditional treatment for metastatic prostate cancer has not included direct treatment of the primary tumor in the prostate. For men with new or recurrent metastatic prostate cancer, research from the CHAARTED trial found that men lived longer if they were treated with chemotherapy when they started hormone shots. Read more about the study here. Visit the ZERO newsroom for more prostate cancer news.

Watch as ZEROs CEO, Jamie Bearse, discusses new prostate cancer treatment news:

Treatments for patients with metastatic prostate cancer are very new, with most of all have been approved within the last five years. These drugs work to control the cancer and include:

• Zytiga
• A treatment used with steroids to shut the adrenal glands while avoiding the effects of the adrenal glands being shut down and prolongs life. This drug can be used in men before chemotherapy.

Xtandi

Xgeva

Rubraca

Olaparib

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.

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Pembrolizumab Given After Surgery Reduces Risk Of Kidney Cancer Recurrence

Who does this study affect: People with clear cell kidney cancer that has a higher chance of coming back after surgery.

What did this study find: An early analysis of the data in the phase 3 KEYNOTE-564 clinical trial shows that pembrolizumab given after surgery may lower the risk of recurrence for clear cell renal cell carcinoma .

Clear cell RCC is the most common type of kidney cancer. Clear cell RCC accounts for about 70% of all kidney cancers. For many people, the first treatment for RCC is surgery to remove part or all of the affected kidney, which is called a partial or radical nephrectomy. However, for up to 40% of people with RCC, the cancer will come back, or recur, after surgery and often the recurrent disease will have spread to other parts of the body, which is called metastasis. To prevent the kidney cancer from coming back, many people are offered adjuvant treatment, which is a treatment given after surgery to destroy any remaining cancer cells that are in the body but undetectable. The adjuvant treatments currently available for kidney cancer include radiation therapy, chemotherapy, and targeted therapy, but they are not always effective.

Serious side effects were more common among those who received pembrolizumab than in those who received the placebo .

lead study author Tony Choueiri, MD Dana Farber Cancer Institute

More Chemotherapy Does Not Help People With Locally Advanced Cervical Cancer Live Longer

Who does this study affect: People with locally advanced cervical cancer.

What did this study find: The phase 3 OUTBACK clinical trial found that adjuvant chemotherapy given after treatment with chemoradiation did not help people with locally advanced cervical cancer live longer. Treatment given after the main treatment is called adjuvant treatment.

Locally advanced cervical cancer means it has spread beyond the cervix but not to other parts of the body. The main standard treatment option for locally advanced cervical cancer is chemoradiation. Chemoradiation is a combination of chemotherapy and radiation therapy. It can be used alone or combined with surgery to treat the cancer. However, about 1 out of every 3 people who receive chemoradiation still experiences a recurrence, which is when the cancer has come back. Recurrent cervical cancer can spread to other parts of the body, called metastasis, and this can be life-threatening. For this reason, many people with cervical cancer have been given more chemotherapy after standard chemoradiation in an effort to lower the risk of recurrence.

What does this mean for patients: More chemotherapy after standard chemoradiation for locally advanced cervical cancer does not help people live longer and can lower patients quality of life.

lead study author Linda R. Mileshkin, MD Peter MacCallum Cancer Centre

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Your Cancer Care Team

People with cancer should be cared for by a multidisciplinary team . This is a team of specialists who work together to provide the best care and treatment.

The team often consists of specialist cancer surgeons, oncologists , radiologists, pathologists, radiographers and specialist nurses.

Other members may include physiotherapists, dietitians and occupational therapists. You may also have access to clinical psychology support.

When deciding what treatment is best for you, your doctors will consider:

• the type and size of the cancer
• what grade it is
• whether the cancer has spread to other parts of your body

Newer Treatments For Early

Researchers are looking at newer forms of treatment for early-stage prostate cancer. These new treatments could be used either as the first type of treatment or after unsuccessful radiation therapy.

One treatment, known as high-intensity focused ultrasound , destroys cancer cells by heating them with highly focused ultrasonic beams. This treatment has been used in some countries for a while, and is now available in the United States. Its safety and effectiveness are now being studied, although most doctors in the US dont consider it to be a proven first-line treatment for prostate cancer at this time.

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Radiotherapy To Primary Tumor

The role of the treatment of the primary tumor is recognized in metastatic renal cancer . The HORRAD and STAMPEDE trials addressed the efficacy of this strategy in mHSPC . In the HORRAD trial, 432 men with newly-diagnosed HSPC, PSA > 20 ng/mL and bone metastases, were randomized to receive ADT with or without prostate radiotherapy . Median time to PSA progression was longer in the radiotherapy group compared to ADT alone p = 0.02). Data on OS resulted inconclusive ), but this trial raised the possibility that survival might be improved in a subgroup of patients with fewer than five bone metastases ).

In the STAMPEDE trial, a cohort of 2,061 patients with newly diagnosed mHSPC were randomized to receive the standard of care or standard of care plus radiotherapy to the primary tumor . Upfront docetaxel was allowed, but only 18% of patients received chemotherapy in addition to ADT. Radiotherapy to the primary was started within 34 weeks after the last docetaxel dose . Radiotherapy improved failure-free survival p< 0.0001), but not OS p = 0.266). However, in the pre-specified analysis, the low-volume subgroup, as per CHAARTED criteria , had significant benefit in both failure-free and overall survival .

Metastatic Prostate Cancer Comes In Two Forms Which Could Guide Treatment

Date:

University of Wisconsin-Madison

Summary:

Scientists have identified two subtypes of metastatic prostate cancer that respond differently to treatment, information that could one day guide physicians in treating patients with the therapies best suited to their disease.

Scientists have identified two subtypes of metastatic prostate cancer that respond differently to treatment, information that could one day guide physicians in treating patients with the therapies best suited to their disease.

Building off of earlier studies that discovered clinically relevant subtypes of breast cancer and non-metastatic prostate cancer, researchers identified genetic signatures that can divide metastatic prostate tumors into two types known as luminal and basal.

Luminal tumors responded better to testosterone-blocking treatments, while basal tumors did not benefit as much from this hormone treatment. Basal tumors also included the particularly aggressive form of metastatic disease known as small cell neuroendocrine prostate cancer. Further clinical trials will be required before any new diagnostic-based treatment selection is available.

With colleagues at the University of California, San Francisco and other institutions, Zhao published his findings Sept. 23 in the journal JAMA Oncology. The work was co-led by Rahul Aggarwal of UCSF and Nicholas Rydzewski in the Department of Human Oncology at SMPH.

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