Tuesday, January 31, 2023

First Line Treatment For Metastatic Prostate Cancer

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Your Cancer Care Team

First-Line Treatment of HER2-Positive Metastatic Breast Cancer

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

In Five Years A Major Treatment Shift

In men diagnosed with metastatic hormone-sensitive prostate cancer, the cancer is typically driven to grow and spread by androgens that are produced largely in the testes. For many years, treatments that block androgen production have been a mainstay for men initially diagnosed with metastatic prostate cancer.

Starting in 2014, that began to change after a large clinical trial showed that adding the chemotherapy drug docetaxel to ADT improved how long men with hormone-responsive disease lived. Shortly after, another clinical trial showed that adding abiraterone to ADT also improved survival in these men, although primarily in men with many metastatic tumors, known as high-volume disease.

However, docetaxel, which works by directly killing cancer cells, can have substantial side effects, and some patients arent healthy enough to tolerate it. And abirateronewhich blocks androgen production throughout the bodycan also cause side effects, including those that affect the liver. It also has to be given in combination with the steroid prednisone, which carries its own toxicity.

Doing so, Dr. Chi said during a presentation of the TITAN data at the ASCO meeting, might help stave off the typically inevitable development of hormone-resistant cancer, which is more difficult to treat and a key driver of prostate cancer deaths.

Early Evaluation And Counseling

1. In patients with suspicion of advanced prostate cancer and no prior histologic confirmation, clinicians should obtain tissue diagnosis from the primary tumor or site of metastases when clinically feasible.

2. Clinicians should discuss treatment options with advanced prostate cancer patients based on life expectancy, comorbidities, preferences, and tumor characteristics. Patient care should incorporate a multidisciplinary approach when available.

3. Clinicians should optimize pain control or other symptom support in advanced prostate cancer patients and encourage engagement with professional or community-based resources, including patient advocacy groups.

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What Makes Immucuras Cell Based Immunotherapy So Special

Cell based Immunotherapy can be the last hope for many cancer patients. Its effectiveness depends on the strength of the patients immune system. And of course, we dont simply assume that the cancer patients immune system is strong. We have found a way to make the immune system more receptive and smarter. Seriously ill patients can then also benefit from immunotherapy with dendritic cells.Dr. Ramon Simon-Lopez

New Radioactive Drugs Destroy Aggressive And Metastatic Cancer Cells

Definition Of Visceral Metastases In Prostate Cancer

In addition to radium and samarium, new radioactive drugs, experimental 177-lutetium-PSMA- and 225-actinium-PSMA*, have now been discovered. Docrates Cancer Center was the first in the Nordic countries to launch the new 177-lutetium-PSMA treatment under special permission in early 2017 for the treatment of patients whose hormonal and other basic treatments designed to prevent recurrence are no longer effective. So far, Docrates has administered 177-lutetium-PSMA treatments to about 100 men. Thousands of men have been treated around the world as the treatment has been available in or outside clinical trials in five countries around the world in addition to Finland.

In Finland, 177-lutetium-PSMA treatments have also been provided at the Helsinki University Hospital as experimental treatment outside clinical trials.

177-lutetium-PSMA- and 225-actinium-PSMA treatments are based on the PSMA molecule that occurs in abundance on the surface of aggressive and metastatic cancer cells. The 177-lutetium-PSMA and 225-actinium-PSMA drugs reach the surface of these active cancer cells directly, guided by the carrier drug and regardless of their location, and locally destroy them using radioactive radiation. The 177-lutetium-PSMA- and 225-actinium-PSMA treatments require an examination using tracer imaging to confirm the PSMA positivity of the cancer cells.

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Multidisciplinary Nature Of Treatment In Todays Advanced Prostate Cancer Care Paradigm

As the therapeutic landscape evolves to include increasingly complex combinations of systemic therapies with or without local therapies, advances in imaging, and germline and somatic genetic testing, treating men with advanced prostate cancer is increasingly one that must embrace multidisciplinary management approaches. Team members should include urologists, medical oncologists, and radiation oncologists at a minimum when supporting treatment decisions for advanced disease. Additional specialists may also include genitourinary pathology, genetic counseling, palliative care, and holistic specialists, as appropriate, in addition to primary care. Best practices must also include clinicians comfortable describing the use of germline and somatic genetic testing, and when advanced imaging techniques could be optimally used or avoided. Radiologists and nuclear medicine specialists are valuable in helping to accurately interpret scans. Palliative care team members may also play a key role when treating men with symptomatic metastatic disease. Palliative care itself is an interdisciplinary, holistic approach to managing an advanced disease such as prostate cancer with a guarded prognosis. It can include controlling symptoms that are physical, psychological, spiritual, and social. The goal of palliation is to prevent and relieve suffering and to support the best possible QOL for the patient and family.

Peer Review And Document Approval

An integral part of the guideline development process at the AUA is external peer review. The AUA conducted a thorough peer review process to ensure that the document was reviewed by experts in the diagnosis and management of Advanced Prostate Cancer. In addition to reviewers from the AUA PGC, Science and Quality Council , and Board of Directors , the document was reviewed by representatives from ASTRO, SUO, and ASCO as well as external content experts. Additionally, a call for reviewers was placed on the AUA website from December 2-16, 2019 to allow any additional interested parties to request a copy of the document for review. The guideline was also sent to the Urology Care Foundation and representation from prostate cancer advocacy to open the document further to the patient perspective. The draft guideline document was distributed to 96 peer reviewers. All peer review comments were blinded and sent to the Panel for review. In total, 44 reviewers provided comments, including 34 external reviewers. At the end of the peer review process, a total of 522 comments were received. Following comment discussion, the Panel revised the draft as needed. Once finalized, the guideline was submitted for approval to the AUA PGC, SQC, and BOD as well as the governing bodies of ASTRO and SUO for final approval.

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Cemiplimab Makes Case As First

Tony BerberabeTargeted Therapies in Oncology

After 3 years of follow-up, findings from the EMPOWER-Lung1 trial demonstrated further improvement in overall survival , progression-free survival , and overall response rate in patients with advanced or metastatic nonsmall cell lung cancer. Patients were given cemiplimab-rwlc vs chemotherapy and continued to see improvements in OS despite a crossover rate of 75%, according to data presented by Mustafa Özgürolu, MD, during the International Association for the Study of Lung Cancer 2022 North America Conference on Lung Cancer.1

In the second part of the trial, patients were allowed to continue cemiplimab therapy with the addition of histologic-specific chemotherapy beyond progression this resulted in durable responses and an ORR of 31.3%. In patients with PD-L1 greater than or equal to 50%, patients in the cemiplimab arm had a median OS of 26.1 months vs 13.3 months in the chemotherapy arm Risk of death was 43% .

Similarly, PFS rates favored patients in the cemiplimab arm. Median PFS was 8.1 months in the treatment arm vs 5.3 months in the control arm . Risk of progression was 49% .

ORR and duration of response also favored cemiplimab over chemotherapy with patients treated with cemiplimab with an ORR of 46.5% vs 21.0% in patients treated with chemotherapy .

REFERENCE

What Is Dendritic Cell Therapy

New treatment options in metastatic prostate cancer

Although Dendritic cells were discovered in the 19th century, it was only at the beginning of the 21st century that their role in adaptive immunity was discovered. Ralph M. Steinman understood that the primed dendritic cells were capable of detecting and destroying malignant cancer cells in the body and for his work he was awarded the Nobel prize in Medicine in 2011.

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How Does Immunotherapy Work

Since 2014, Immucura has been helping patients to fight cancer with the most advanced scientific breakthroughs in Cancer Health. Immunotherapies have proven to be a very effective, minimally non-invasive weapon against cancer. They are the key elements in Immucuras integrative approach. Immucura is specialised in Dendritic Cell Therapy , as well as Macrophage Activation Therapy , Natural Killer Cell Therapy and Nanothermia. We also offer blood analysis, nutritional advice, targeted supplementation and other complementary treatments.

Treatments To Help Manage Symptoms

Advanced prostate cancer can cause symptoms, such as bone pain. Speak to your doctor or nurse if you have symptoms there are treatments available to help manage them. The treatments above may help to delay or relieve some symptoms. There are also specific treatments to help manage symptoms you may hear these called palliative treatments. They include:

This is the team of health professionals involved in your care. It is likely to include:

  • a specialist nurse
  • a chemotherapy nurse
  • a diagnostic radiographer
  • a therapeutic radiographer
  • other health professionals, such as a dietitian or physiotherapist.

Your MDT will meet to discuss your diagnosis and treatment options. You might not meet all the health professionals straight away.

Your main point of contact might be called your key worker. This is usually your clinical nurse specialist , but might be someone else. The key worker will co-ordinate your care and help you get information and support. You may also have close contact with your GP and the practice nurses at your GP surgery.

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If Treatment Does Not Work

Recovery from cancer is not always possible. If the cancer cannot be cured or controlled, the disease may be called advanced or terminal.

This diagnosis is stressful, and for some people, advanced cancer may be difficult to discuss. However, it is important to have open and honest conversations with your health care team to express your feelings, preferences, and concerns. The health care team has special skills, experience, and knowledge to support patients and their families and is there to help. Making sure a person is physically comfortable, free from pain, and emotionally supported is extremely important.

People who have advanced cancer and who are expected to live less than 6 months may want to consider hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to talk with the health care team about hospice care options, which include hospice care at home, a special hospice center, or other health care locations. Nursing care and special equipment, including a hospital bed, can make staying at home a workable option for many families. Learn more about advanced cancer care planning.

After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and loss.

Antiandrogens For Prostate Cancer

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These prostate cancer drugs work by blocking the effect of testosterone in the body. Antiandrogens are sometimes used in addition to orchiectomy or LHRH analogs.This is due to the fact that the other forms of hormone therapy remove about 90% of testosterone circulating in the body. Antiandrogens may help block the remaining 10% of circulating testosterone. Using antiandrogens with another form of hormone therapy is called combined androgen blockade , or total androgen ablation. Antiandrogens may also be used to combat the symptoms of flare . Some doctors prescribe antiandrogens alone rather than with orchiectomy or LHRH analogs.

Available antiandrogens include abiraterone acetate , apalutamide , biclutamide , darolutamide , enzalutamide , flutamide , and nilutamide . Patients take antiandrogens as pills. Diarrhea is the primary side effect when antiandrogens are used as part of combination therapy. Less likely side effects include nausea, liver problems, and fatigue. When antiandrogens are used alone they may cause a reduction in sex drive and impotence.

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Adding Enzalutamide To Standard First

ASCO PerspectiveWe see here that giving enzalutamide early can offer worthwhile benefits, especially for certain groups of men. In addition to helping men live longer overall, this approach means they can also likely go longer without having to take steroids or receive chemotherapy, said ASCO Expert Neeraj Agarwal, MD.

CHICAGO An interim analysis of the international randomized, phase III ENZAMET trial found that 80% of men with metastatic hormone-sensitive prostate cancer who received the non-steroidal anti-androgen medicine enzalutamide along with the standard of care treatment were alive after 3 years compared with 72% of men who received other NSAAs along with standard treatment. The study was led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group.

These findings will be presented in ASCOs Plenary Session, which features four studies of great importance to patient care, out of the 5,600 abstracts accepted to the 2019 American Society of Clinical Oncology Annual Meeting.

Physicians and patients with prostate cancer now have a new treatment option with enzalutamide, and this is especially relevant for men who cannot tolerate chemotherapy and have a lower burden of disease seen on scans, said study co-chair Christopher Sweeney, MBBS, a medical oncologist at the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA.

Study at a Glance

Performance Status And Predicted Life Expectancy

Performance status and predicted life expectancy are both critical elements to incorporate into individualized clinical decision-making in men with advanced prostate cancer. Performance status remains a key factor in treatment decision-making, particularly among men with advanced prostate cancer. Indeed, performance status has been found to be strongly associated with survival among men with mCRPC, 35-38 and has been used to define index patients in prior versions of this guideline. Performance status generally describes an individual patients level of functioning and how ones disease impacts a patients activities of daily living. The first of two commonly used scales to evaluate performance status include the Eastern Cooperative Oncology Group scale from 0 to 5 where 0 is fully functional and 5 is dead. The second is the Karnofsky scale where 10 represents a moribund individual and 100 represents an individual with no limitations.

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Standards Of Care In Hormone Therapy

Most doctors agree that hormone therapy is the most effective treatment available for patients with advanced prostate cancer. However, there is disagreement on exactly how and when hormone therapy should be used. Here are a few issues regarding standards of care:

Timing of Cancer Treatment

The disagreement is due to conflicting beliefs. One is that hormone therapy should begin only after symptoms from the metastases, like bone pain, occur. The counter belief is that hormone therapy should start before symptoms occur. Earlier treatment of prostate cancer is associated with a lower incidence of spinal cord compression, obstructive urinary problems, and skeletal fractures. However, survival is not different whether treatment is started early, or deferred.

The only exception to the above, is in lymph node-positive, post-prostatectomy patients, given androgen deprivation as an adjuvant immediately after surgery. In this situation, immediate therapy resulted in a significant improvement in progression free survival, prostate cancer specific survival, and overall survival.

Length of Cancer Treatment

The disagreement in this situation is between continuous androgen deprivation and intermittent androgen deprivation.

Combination vs. Single-Drug Therapy

Patients With Diabetes Mellitus

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Baseline Characteristics

At baseline, 121 , 47 , and 100 patients had diabetes mellitus in the abiraterone, enzalutamide, and docetaxel groups, respectively in each treatment group, a lower proportion of those with diabetes mellitus had diabetes mellitus type 1 than diabetes mellitus type 2 .

The median time from initial diagnosis to study start was 5.7 , 4.0 , and 5.4 years in the abiraterone, enzalutamide, and docetaxel groups, respectively. Median age at baseline was 77.0 , 77.0 , and 69.0 years, respectively . A Gleason score of 810 at diagnosis was reported in 47.7%, 55.8%, and 49.0% of these treatment groups, respectively . The following important concomitant co-morbidity types were reported in the diabetes mellitus group for patients receiving abiraterone, enzalutamide, and docetaxel, respectively: cardiovascular in 102 , 36 , and 85 patients neurologic in 13 , 4 , and 12 patients and renal in 10 , 12 , and 7 patients . Details regarding treatment history at study inclusion are presented in Supplementary Table S4B.

Treatment Exposure

Efficacy Outcomes

According to KaplanMeier estimates, the median time to progression was 12.0 , 10.3 , and 7.7 months with abiraterone, enzalutamide, and docetaxel, respectively . The median OS was 30.8 , 27.1 , and 24.3 months in these treatment groups, respectively .

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Biochemical Recurrence Without Metastatic Disease After Exhaustion Of Local Treatment Options

Prognosis

4. Clinicians should inform patients with PSA recurrence after exhaustion of local therapy regarding the risk of developing metastatic disease and follow such patients with serial PSA measurements and clinical evaluation. Clinicians may consider radiographic assessments based on overall PSA and PSA kinetics.

5. In patients with PSA recurrence after exhaustion of local therapy who are at higher risk for the development of metastases , clinicians should perform periodic staging evaluations consisting of cross-sectional imaging and technetium bone scan.

6. Clinicians may utilize novel PET-CT scans in patients with PSA recurrence after failure of local therapy as an alternative to conventional imaging or in the setting of negative conventional imaging.

Treatment

7. For patients with a rising PSA after failure of local therapy and no demonstrated metastatic disease by conventional imaging, clinicians should offer observation or clinical trial enrollment.

8. ADT should not be routinely initiated in this population . However, if ADT is initiated in the absence of metastatic disease, intermittent ADT may be offered in lieu of continuous ADT.

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