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Orchiectomy Vs Hormone Therapy Prostate Cancer

Recommendation For Routine Testosterone Testing

Hormone Therapy & Advanced Therapies for Prostate Cancer, Celestia Higano, MD | 2021 Mid-Year Update

T levels should be measured regularly in men receiving ADT to ensure T suppression is being maintained to target this does not appear to be the case in routine clinical practice. EAU guidelines recommend that T testing is performed 3 months after the first dose of ADT and repeated every 36 months thereafter. ADT use is often assumed to be a proxy for adequate T suppression to castrate levels however, neglecting to assess T will fail to identify levels above target, microsurges, and escapes. Adding a T test to the regular PSA assessment is simple to implement and would address these concerns.

With a rise in PSA and progression to CRPC, T testing and management remain important. Confirmation that T is castrate at time of CRPC diagnosis is critical, and continuance of regular testing should confirm effective T suppression and prevention of repopulation of partially androgen-sensitive tumor cells. An incorrect diagnosis of CRPC may prompt the use of additional, more costly, and possibly more toxic therapies in patients who do not yet require them .

Therapies That Interfere With Androgen Function

Taken daily as pills, antiandrogens bind to the androgen receptor proteins in the prostate cells, preventing the androgens from functioning. In addition to preventing a flare reaction, antiandrogens may be added to your treatment plan if an orchiectomy, LHRH agonist or LHRH antagonist is no longer working by itself. Commonly prescribed antiandrogens include flutamide and bicalutamide .

Enzalutamide is a newer type of antiandrogen that blocks the signal that the receptor normally sends to the cells control center to trigger growth and division. This antiandrogen may be used to treat castration-resistant prostate cancer.

When Is Hormone Therapy Used

Hormone therapy may be used:

  • If the cancer has spread too far to be cured by surgery or radiation, or if you cant have these treatments for some other reason
  • If the cancer remains or comes back after treatment with surgery or radiation therapy
  • Along with radiation therapy as the initial treatment, if you are at higher risk of the cancer coming back after treatment
  • Before radiation to try to shrink the cancer to make treatment more effective

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Evolving View Of Suppression Targets For Testosterone

Historically, the definition of castration has been suppression of T to a level lower than 50ng/dL, based on radioimmunoassays developed in the 1960s that were less accurate when measuring lower levels of T. Advances in assay technology with greater sensitivities confirm that T levels following bilateral orchiectomy are approximately 15ng/dL .

A much less common form of PCa is small cell carcinoma that is highly malignant, presents with low PSA levels and has little dependency on AR signaling patients with this tumor do not usually benefit from ADT . Neuroendocrine differentiation can also occur in PCa that may lead to castration resistance before any rise in PSA .

There is increasing evidence that very low nadir T levels, particularly during the first few months of ADT, and absence of microsurges and escapes in T may be associated with improved clinical outcomes, including survival . This confirms the critical role of T in stimulation of PCa cells and emphasizes the importance of selecting an ADT with the greatest impact on T levels. During therapy, T should be monitored frequently to confirm achievement of targets, ideally to < 20ng/dL if not, consideration should be given to improving patient compliance or selecting an alternative ADT.

Comparing Chemical And Surgical Castration For Prostate Cancer

Mechanisms of Prostate Cancer Progression (mCRPC)

JAMA OncologyChemical or Surgical CastrationIs This Still an Important Question?


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JAMA Oncology

Surgical castration to remove the testicles of men with metastatic prostate cancer was associated with lower risks for adverse effects compared with men who underwent medical castration with gonadotropin-releasing hormone agonist therapy, according to an article published online by JAMA Oncology.

Androgen-deprivation therapy , which is achieved through surgical or medical castration, has been a cornerstone in the management of metastatic prostate cancer for the past 50 years. But the use of bilateral orchiectomy has been nearly eliminated in the U.S. because of cosmetic and psychological concerns.

Of the 3,295 men, 87 percent were treated with GnRHa and 13 percent were treated with orchiectomy. The overall three-year survival was 46 percent for GnRHa treatment and 39 percent for orchiectomy.

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Early Versus Delayed Treatment

For men who need hormone therapy, such as men whose PSA levels are rising after surgery or radiation or men with advanced prostate cancer who dont yet have symptoms, its not always clear when it is best to start hormone treatment. Some doctors think that hormone therapy works better if its started as soon as possible, even if a man feels well and is not having any symptoms. Some studies have shown that hormone treatment may slow the disease down and perhaps even help men live longer.

But not all doctors agree with this approach. Some are waiting for more evidence of benefit. They feel that because of the side effects of hormone therapy and the chance that the cancer could become resistant to therapy sooner, treatment shouldnt be started until a man has symptoms from the cancer. This issue is being studied.

How Are Treatments Administered

GnRH agonists are either injected or placed as small implants under the skin. Anti-androgens are taken as a pill once per day. Degarelix is given as an injection. A chemotherapy drug called docetaxel is sometimes used in combination with these hormone therapies.

Zytiga is taken by mouth once per day in combination with a steroid called prednisone.

Surgery to remove the testicles can be done as an outpatient procedure. You should be able to go home a few hours after an orchiectomy.

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What Types Of Hormone Therapy Are There

There are two basic kinds of hormone therapy for prostate cancer. One class of drugs stops the body from making certain hormones. The other allows the body to make these hormones, but prevents them from attaching to the cancer cells. Some doctors start treatment with both drugs in an effort to achieve a total androgen block. This approach goes by several names: combined androgen blockade, complete androgen blockade, or total androgen blockade.

Here’s a rundown of the techniques.

Hormone therapy for prostate cancer can cause bone thinning osteoporosis, which can lead to broken bones. However, treatment with bisphosphonates — like Aredia, Fosamax, and Zometa — may help prevent this condition from developing, says Holden.

What Are The Side Effects Of Hormone Therapy For Prostate Cancer

The Cardiovascular Effects of Orchiectomy Versus LHRH Agonists

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.

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    Hormone Treatment Fights Prostate Cancer

    Hormone therapy for prostate cancer has come a long way in the past few decades. Not so long ago, the only hormonal treatment for this disease was drastic: an orchiectomy, the surgical removal of the testicles.

    Now we have a number of medications — available as pills, injections, and implants — that can give men the benefits of decreasing male hormone levels without irreversible surgery.

    “I think hormonal therapy has done wonders for men with prostate cancer,” Stuart Holden, MD, Medical Director of the Prostate Cancer Foundation.

    Hormone therapy for prostate cancer does have limitations. Right now, it’s usually used only in men whose cancer has recurred or spread elsewhere in the body.

    But even in cases where removing or killing the cancer isn’t possible, hormone therapy can help slow down cancer growth. Though it isn’t a cure, hormone therapy for prostate cancer can help men with prostate cancer feel better and add years to their lives.

    On average, hormone therapy can stop the advance of cancer for two to three years. However, it varies from case to case. Some men do well on hormone therapy for much longer.

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    What Have I Learned By Reading This

    You learned about:

    If you have any questions, please talk to your doctor or healthcare team. It is important that you understand what is going on with your treatment. This knowledge will help you take better care of yourself and feel more in control so that you can get the most from your treatment..

    • The results of any tests you have taken such as your Prostate-Specific Antigen test.
    • When you found out you had prostate cancer.
    • Information on the kinds of treatment you have had for your prostate cancer including:
    • The places and dates where you had your treatment.
    • What type of treatment you had. And,
    • Any medicines you took before, during, and after your prostate cancer treatment.
  • Contact information for all your doctors and the other members of your health care team who helped with your prostate cancer treatment and followup care.
  • Any side effects or problems you had during and after your prostate cancer treatment.
  • Any supportive care you got during your treatment. Supportive care is treatment given to keep, control, or make your side effects better and to make your life better. For example, pain medicine, emotional support, and nutritional supplements.
    • What hormone therapy is

    Drugs In Development Targeting The Androgen Pathway

    Molecular and cellular mechanisms of castration resistant prostate ...

    Other ADT drugs include darolutamide and relugolix that are not yet approved. Darolutamide is an oral, nonsteroidal antiandrogen with a similar mode of action to enzalutamide and apalutamide. In a 12-week phase 2 study, darolutamide demonstrated a PSA response rate of 29% in the low, 33% in the mid, and 33% in the highest dose group .

    Relugolix is an oral GnRH antagonist in phase 3 development. In healthy males the drug was readily absorbed and reduced mean serum T levels within 6h of dosing however, a food effect reduced exposure by 50%. T recovered rapidly following cessation of treatment .

    Patients may prefer oral dosing over injections due to the convenience of not requiring a clinic visit for injections and the avoidance of injection-site AEs however, there may be disadvantages. Compliance with oral dosing is rarely 100%, especially for long-term treatments where dosing may be required for months or years and particularly where the underlying illness is asymptomatic. Missed doses may compromise efficacy, which may be critical when the illness is serious or life threatening e.g., use of statins or antihypertensives in patients with cardiovascular disease and dosing of cancer treatments . With ADT, this issue can be avoided and 100% compliance achieved if the therapy is given on schedule via long-acting injection. Due to the high daily doses of drug required for the androgen pathway inhibitors, depot injections may not be feasible.

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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 .

    Comparing Chemical Surgical Castration For Prostate Cancer

    The JAMA Network Journals
    Surgical castration to remove the testicles of men with metastatic prostate cancer was associated with lower risks for adverse effects compared with men who underwent medical castration with gonadotropin-releasing hormone agonist therapy, according to an article.

    Surgical castration to remove the testicles of men with metastatic prostate cancer was associated with lower risks for adverse effects compared with men who underwent medical castration with gonadotropin-releasing hormone agonist therapy, according to an article published online by JAMA Oncology.

    Androgen-deprivation therapy , which is achieved through surgical or medical castration, has been a cornerstone in the management of metastatic prostate cancer for the past 50 years. But the use of bilateral orchiectomy has been nearly eliminated in the U.S. because of cosmetic and psychological concerns.

    Of the 3,295 men, 87 percent were treated with GnRHa and 13 percent were treated with orchiectomy. The overall three-year survival was 46 percent for GnRHa treatment and 39 percent for orchiectomy.

    The study indicates surgical castration through orchiectomy was associated with lower risks of any fractures, peripheral artery disease and cardiac-related complications compared with medical castration with GnRHa. No statistically significant difference was found between orchiectomy and GnRHa for diabetes and cognitive disorders.

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    If Treatment Does Not Work

    Intermittent Hormone Therapy for Prostate Cancer 101 | Ask a Prostate Expert, Mark Scholz, MD

    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.

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