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Metastatic Hormone Resistant Prostate Cancer

What Are The Side Effects Of Hormone Therapy For Prostate Cancer

Prostate Cancer: Research shows new treatment option offers improved survival

Because androgens affect many other organs besides the prostate, ADT can have a wide range of side effects , including:

  • loss of interest in sex
  • Studer UE, Whelan P, Albrecht W, et al. Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer Trial 30891. Journal of Clinical Oncology 2006 24:18681876.

  • Zelefsky MJ, Eastham JA, Sartor AO. Castration-Resistant Prostate Cancer. In: Vincent T. DeVita J, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology, 9e. Philadelphia, PA: Lippincott Williams & Wilkins 2011.

  • Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer. European Urology 2021 79:150158.

  • Intermittent Versus Continuous Hormone Therapy

    Most prostate cancers treated with hormone therapy become resistant to this treatment over a period of months or years. Some doctors believe that constant androgen suppression might not be needed, so they advise intermittent treatment. This can allow for a break from side effects like decreased energy, sexual problems, and hot flashes.

    In one form of intermittent hormone therapy, treatment is stopped once the PSA drops to a very low level. If the PSA level begins to rise, the drugs are started again. Another form of intermittent therapy uses hormone therapy for fixed periods of time for example, 6 months on followed by 6 months off.

    At this time, it isnt clear how this approach compares to continuous hormone therapy. Some studies have found that continuous therapy might help men live longer, but other studies have not found such a difference.

    How Prostate Cancer Is Treated

    In cancer care, different types of doctorsincluding medical oncologists, surgeons, and radiation oncologistsoften work together to create an overall treatment plan that may combine different types of treatments to treat the cancer. This is called a multidisciplinary team. Cancer care teams include a variety of other health care professionals, such as palliative care experts, physician assistants, nurse practitioners, oncology nurses, social workers, pharmacists, counselors, dietitians, physical therapists, and others.

    The common types of treatments used for prostate cancer are described below. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care.

    Treatment options and recommendations depend on several factors, including the type and stage of cancer, possible side effects, and the patients preferences and overall health.

    Cancer treatment can affect older adults in different ways. More information on the specific effects of surgery, chemotherapy, and radiation therapy on older patients can be found another section of this website.

    Because most prostate cancers are found in the early stages when they are growing slowly, you usually do not have to rush to make treatment decisions. During this time, it is important to talk with your doctor about the risks and benefits of all your treatment options and when treatment should begin. This discussion should also address the current state of the cancer:

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    Treatment To Lower Androgen Levels From Other Parts Of The Body

    LHRH agonists and antagonists can stop the testicles from making androgens, but cells in other parts of the body, such as the adrenal glands, and prostate cancer cells themselves, can still make male hormones, which can fuel cancer growth. Some drugs can block the formation of androgens made by these cells.

    Abiraterone blocks an enzyme called CYP17, which helps stop these cells from making androgens.

    Abiraterone can be used in men with advanced prostate cancer that is either:

    • Castration-resistant

    This drug is taken as pills every day. It doesnt stop the testicles from making testosterone, so men who havent had an orchiectomy need to continue treatment with an LHRH agonist or antagonist. Because abiraterone also lowers the level of some other hormones in the body, prednisone needs to be taken during treatment as well to avoid certain side effects.

    Ketoconazole , first used for treating fungal infections, also blocks production of androgens made in the adrenal glands, much like abiraterone. It’s most often used to treat men just diagnosed with advanced prostate cancer who have a lot of cancer in the body, as it offers a quick way to lower testosterone levels. It can also be tried if other forms of hormone therapy are no longer working.

    Ketoconazole also can block the production of cortisol, an important steroid hormone in the body, so men treated with this drug often need to take a corticosteroid .

    Orteronel Misses Goal In Metastatic Hormone

    Current and Emerging Therapies for Bone Metastatic Castration

    Significant improvement seen in progression-free survival, but not overall survival, with addition of orteronel to androgen deprivation therapy

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    Advanced Prostate Cancer Metastatic Hormone

    This course series Advanced Prostate Cancer gives clinicians a complete view on clinical aspects, diagnosis, and treatments of prostate cancer. This course series contains five courses, each of them addresses an important topic in diagnosis, treatment, and management of prostate cancer. Each course is accredited by the European Accreditation Council for Continuing Medical Education for 1 to 3 European CME credits. The five courses are:

    Course 1: Basis of ADT Course 2: Hormone-sensitive nmPCaCourse 3: Metastatic hormone-sensitive PCaCourse 4: Non-metastatic CRPC Course 5: Metastatic CRPC

    This course Metastatic Hormone-Sensitive Prostate Cancer is the third part of the course series.

    The development of this course has been supported by Jansen with a concession of an unrestricted educational grant.

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    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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    Tailoring Treatment Aims To The Individual Goal

    As alluded to earlier in the review, treatment of the mHSPC patient must take into context the overriding individual treatment aim. For most patients, metastatic prostate cancer is an incurable disease. The aim is to transform mHSPC into a manageable chronic illness so that the patient dies with the cancer, rather than of it.

    For the young patient with few comorbidities presenting with mHSPC, the risk of dying from metastatic prostate cancer is significant. The likely treatment aim is to prolong OS with respect to the cancer. In the absence of a clearly superior agent and prospective sequencing data, the strategy is to maximise the lines of therapies that can be utilized in the patients treatment course. The reasoning of the treating oncologist may be to administer docetaxel in the upfront setting, taking into account that the more tolerable oral antiandrogens can be added on more easily than docetaxel at a later point should the patient become increasingly frail from the disease and/or other underlying comorbidities.

    Does Crpc Affect Different Ethnic/racial Groups Differently

    AR-V7 in Castration Resistant Prostate Cancer

    Non-Hispanic Black people are much more likely to get prostate cancer than those of any other race or ethnicity. Prostate cancer rates are lowest among non-Hispanic Asian Americans. Black people also are more likely than non-Black people to be diagnosed with advanced prostate cancer. But in treatment, Black people have at least similar outcomes compared to non-Black people. Researchers donât fully understand the reasons for these differences.

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    Relevance Of Trial Data In Real

    After decades without significant progress in the treatment landscape of mHSPC, the results of the above-mentioned trials are welcome. Nevertheless, we need to cautiously interpret these results, taking into consideration the between-study heterogeneity in study populations, and how well they reflect our patient population .

    Stage 4 Cancer Explanation

    What are stage 4 metastatic cancers? First of all, before we go to the life expectancy part, you should know more about this stage. As we mentioned above, this is the last or the most severe stage. It means cancer at this stage has a high mortality rate. It can kill the patients most of the time when they receive no proper treatment.

    Why does it have a high mortality rate? You can see it from its name. Cancer in this stage has metastasized. It means the cancer cells have spread and attacked another area or organ outside the initial area where it appears. For example, if you have lung cancer in this stage, the cancer cell has spread to other organs near the lungs, such as the heart and liver.

    Compared to the earliest stage, metastasized cancer is more challenging to treat. We can even call it impossible for certain cases. The cancer cell has grown significantly, so the focused treatment doesnt work for it. Because of that, it is also known for its high mortality rate.

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    Treatments For Metastatic Castration

    Castration-sensitiveprostate cancer is cancer that is being controlled by keeping thetestosterone level as low as would be expected if the testicles were removed. Metastatic prostate cancer is prostate cancer thathas spread to other parts of the body.

    The goal of treatment is to help you live longer and try toimprove your quality of life. Yourhealthcare team will suggest treatments based on your needs and work with youto develop a treatment plan.

    Treatment optionsfor metastatic castration-sensitive prostate cancer may include a combinationof the following:

    • hormone therapy

    Heterogeneity Of Castration Resistance Prostate Cancer

    Convergent evolution of p38/MAPK activation in hormone resistant ...

    Even though the AR plays a major role in the progression to CRPC, alternative pathways can have a role in stimulating prostate cancer cells, confirming the cellular heterogeneity in prostate cancer .

    Prostate cancer cells can develop alternative AR independent molecular pathways for survival that bypass AR activation, including cancer stem cells, receptor tyrosine kinases and neuroendocrine differentiation . A potential mechanism for survival in the castrate environment is the presence of prostate cancer stem cells that continually supply the cancer cell population, despite therapy. These cells are not affected by ADT and can differentiate into androgen dependent and independent cells, leading to a heterogeneous phenotype of AR .

    Activation of the PI3 kinase signaling pathway is critical for the survival of prostate cancer cells. PTEN is a tumor suppressor and has lipid phosphatase activity that metabolizes PIP3 . The PTEN function is expressed primarily through negative regulation of the PI3K/Akt pathway. PTEN is inactivated in several types of cancers, including prostate cancer. Loss of PTEN function in prostate cancer can occur through several mechanisms, including deletion, mutation and methylation. These events can cause tumor cell survival through selective pressure caused by ADT .

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    Surgery And Advanced Prostate Cancer

    An indication for immediate bilateral orchiectomy is spinal cord compression. Surgical intervention is mandatory for pathologic fractures involving weight-bearing bones.

    In patients with clinical stage T3 prostate cancer at initial presentation, radical prostatectomy has not historically been considered beneficial, because of the increased probability of incomplete resection of the cancer, likelihood of micrometastatic disease, and increased morbidity.

    However, a retrospective review of approximately 840 men with stage cT3 prostate cancer who underwent RP at the Mayo Clinic reported outcomes similar to those with organ-confined disease during the same period at this institution. Pathologic stage, Gleason grade, positive surgical margin, and nondiploid chromatin were found to be independently associated with increased progression of disease.

    In another Mayo Clinic study, in which the long-term survival of patients with high-risk prostate cancer was compared after RP and after external beam radiation therapy , RP alone and EBRT plus ADT provided similar long-term cancer control. However, the risk of all-cause mortality was greater after EBRT plus ADT than after RP.

    In the study, RP was used in 1238 men, EBRT plus ADT was used in 344 men, and 265 received EBRT alone. The 10-year cancer-specific survival rates in the study were 92% in patients treated with RP or EBRT plus ADT, and 88% in those receiving EBRT alone, with a median follow-up of 6-10 years.

    Stage 4 Prostate Cancer Clinical Trials

    Clinical trials provide cancer patients with life-extending and curative new medicines. Clinical drug trials are critical in getting new medicines to patients who need them the most, as well as securing data so that regulatory clearances may be secured, and new drugs can enter broad clinical practice. Patients who take part in clinical trials benefit both treatment science and their fellow patients.

    There are currently 100 Phase III drug trials and more than 500 Phase I/II trials related to prostate cancer treatment in progress in the United States alone. Those that are approved will join the 12 new drugs that have been approved for men with advanced/metastatic disease since 2010 and further improve outcomes for patients:

    Using our AI-powered approach, Massive Bio leads patients through the most extensive clinical trial matching process available.

    We can assist you if you have been diagnosed with any of the following prostate cancer subtypes:

    • Transitional Cell Carcinoma
    • Small Cell Carcinoma

    If you do not know which type of prostate cancer you have, that is okay. Additional testing can help you determine your exact diagnosis.

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    Is Metastatic Cancer Always Terminal

    This cancer stage has high mortality risk. However, in most cases, stage 4 or metastatic cancer is not always terminal. It is all depending on the spread area and case. On the other hand, it is also the stage where more advanced and aggressive treatment is necessary to kill the cancer cell.

    Terminal cancer refers to a cancer case that is impossible to cure. This case mostly will result in the death of the patient. Therefore, the treatment for terminal cancer is only to control the spread and ease the patients pain. The curing process is difficult to do. So, it is the period when doctors and patients families prepare for the worst.

    Despite its obvious result, the medical world still sets the standard for the patients survival likelihood. And, to learn more about that matter, you can continue reading. We will start talking about our main topic here, the stage 4 cancer life expectancy.

    Bone Pain In Prostate Cancer

    New Approaches to Metastatic Hormone Sensitive Prostate Cancer

    Many advanced prostate cancer patients often suffer from bone pain that adversely affect quality of life. The management of pain or other cancer related functional impairment is integral part of palliative care. Palliative management can include analgesics, glucocorticoids, palliative chemotherapy, radioisotopes or radiotherapy.

    Radioisotopes that selectively concentrate in bone lesions are approved for the palliative treatment of painful bone metastases. The treatment is of more value in patients with multiple metastases . The radioisotopes have been found to reduce the need for opioid painkillers in such patients.

    EBRT is effective in painful bone lesions in advanced prostate cancer patients but not an ideal option if there are multiple lesions at different sites. The lesions in multiple sites will progress after EBRT in one site and pain will reappear in a short time afterwards, unless other systemic therapies are initiated to control the disease process. Read more on EBRT under prostate cancer treatments.

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    Emerging Treatments Targeting Mcrpc

    Based on the above, there is a crucial need for novel alternative approaches and drugs that could overcome resistance in advanced PCa stages. In fact, several treatments, which are under development and trials, could emerge as promising therapies for patients with mCRPC and become the next-generation standards of care. Table 2 summarizes the evolving targeted treatments in mCRPC along with their relevant clinical trials.

    Ongoing trial interim results show that Ipat prolonged PFSTwo treatment-related deaths occurred in both groups

    ABI: Abiraterone ADC: antibody-drug conjugate AEs: adverse events CAR-T cells: chimeric antigen receptor T cells DDR: DNA-damage repair DOC: docetaxel ENZ: enzalutamide IgG1: immunoglobulin G1 Ipat: ipatasertib LuPSMA: lutetium-177-PSMA-617 MMAE: monomethyl auristatin E OS: overall survival PARPi: poly polymerase inhibitor PFS: progression-free survival PSA: prostate-specific antigen PSA50: > 50% decline in prostate-specific antigen PSMA: prostate-specific membrane antigen RR: response rate TGF: transforming growth factor-.

    Factors That May Influence Treatment Decision

    The drug mechanism of action, the route of administration, the duration of treatment, the impact on quality of life and the toxicity profile are important factors to consider when selecting a therapy for a particular patient, as they are quite different among the various strategies . Docetaxel has a major incidence of myelo-suppression with potential neutropenia, fatigue and neurotoxicity. Abiraterone is associated with mineralocorticoid-associated side effects including hypertension, hypokalemia and hepatic toxicity. Enzalutamide frequently causes fatigue, hypertension and falls. Apalutamide is associated with increased risk of rash, pruritus, hot flushes, hypothyroidism and fractures. Radiotherapy to the primary tumor can cause acute and late bladder and bowel toxic effects that can remarkably affect the quality of life .

    In terms of costs, docetaxel in combination with ADT is likely to be the most cost-effective treatment option for patients with mHSPC . Docetaxel is administered every 21 days for six cycles at an approximate cost of $550 per cycle, whereas novel ARSi are prescribed as a daily dosing schedule until the time of progression at an approximate cost that exceeds $7000 per month . To administer lower dosages of ARSi might be an opportunity to reduce toxicities and costs, but phase 3 non-inferiority trials are still needed .

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