Hormone Therapy For Prostate Cancer Before Radiotherapy

Systemic Therapy For Metastatic Disease

The most common use of hormone therapy today is to treat men whose prostate cancer has metastasized to other parts of the body. If prostate cancer cells escape the prostate, they migrate first to surrounding structures, such as the seminal vesicles and lymph nodes, and later to the bones or, rarely, to other soft tissues.

Hormone therapy is recommended as a palliative treatment, to relieve symptoms such as bone pain. And while hormone therapy is not a cure, in that it cant eliminate prostate cancer completely, it often extends life for many years. By reducing testosterone levels, hormone therapy can shrink a prostate tumor and its metastases and slow further progression of the cancer for so long that sometimes a man with this disease dies of something other than prostate cancer.

Study Population And Characteristics

During the study period, 373 patients diagnosed with IR prostate cancer were treated in the Radiation Oncology Department of the CSMC 196 patients were treated with RT with concomitant short-term ADT, and 177 patients with RT alone. Table shows population and treatment-related characteristics of patients treated with RT and short-term ADT and RT alone. Patients in both arms were similar in terms of mean age at time of therapy, Gleason score at biopsy, fiducials implants, RT treatment modality , and the Charlson comorbidity score. The mean follow-up time was 55.9±37.2months and did not significantly differed between the two treatment groups. However, compared to patients treated with RT alone, patients treated with a combination of RT+ ADT had significantly more unfavorable risk factors including: higher PSA levels before RT treatment, more intermediate-risk risk factors, and a higher percent of positive cores on biopsy. Moreover, patients receiving RT and ADT had higher T-stage, however the difference did not reach statistical significance . The vast majority of patients in both groups did not receive pelvic lymph node RT , and a higher fraction of patients receiving RT and ADT were administered pelvic lymph node RT.

Table 1 Patient characteristics and treatment

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Biochemical Recurrence And Hormone Therapy

Hormone therapy is the standard of care for patients with metastatic prostate cancer, but for patients whose only sign of cancer recurrence is a rising PSA level , the benefits are less clear.

Some doctors think that hormone therapy works better if its started as soon as possible, even if a man is not having any symptoms. Other doctors feel that, because of the side effects of hormone therapy and the chance that the cancer could become resistant to the therapy, treatment shouldnt be started until symptoms develop. This issue is being actively studied.

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Will Side Effects Limit What I Can Do

What you are able to do will depend on which side effects you have and how bad they are. Many men are able to work, cook meals, and enjoy their usual daily activities when they have hormone therapy for their prostate cancer. Other men find that they need more rest than before they started hormone therapy so they cant do as much. You should try to keep doing the things you enjoy as long as you dont get too tired.

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Hormone Therapy Plus Radiation Therapy With Or Without Combination Chemotherapy In Treating Patients With Prostate Cancer

RATIONALE: Hormones can stimulate the production of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy plus radiation therapy is more effective with or without combination chemotherapy for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy plus radiation therapy with or without combination chemotherapy in treating patients who have prostate cancer.

OBJECTIVES:

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Table : Boosting The Effectiveness Of Radiation Therapy

A randomized controlled study involving 206 men with early-stage prostate cancer evaluated whether adding six months of hormone therapy to external-beam radiation treatment would boost both overall survival and disease-free survival . The results are given below. The same research group found, in an earlier study, that the addition of hormone therapy was of most benefit to men who were considered at moderate or high risk, based on their clinical profile.

Five-year follow-up 82% Source: Journal of the American Medical Association, 2004 292:8217. PMID: 15315996.

Combined with radiation therapy. A number of studies have shown that men with early-stage prostate cancer are more likely to be cured when hormone therapy is given in conjunction with radiation therapy . Even when the disease is regionally advanced, meaning that it has progressed to tissues immediately surrounding the prostate gland, neoadjuvant hormone therapy reduces risk of progression and relapse .

Addition Of Hormone Therapy To Radiotherapy Benefits Men With Localized Prostate Cancer

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The addition of androgen deprivation therapy to radiotherapy improved survival outcomes among patients with localized prostate cancer, according to study results published in TheLancet Oncology.

Additionally, prolonging the adjuvant component of ADT provided significant benefit regardless of radiotherapy dose among those with intermediate-risk and high-risk disease, researchers noted.

Lancet Oncol

Rationale

Prostate cancer is an extremely common cancer worldwide that has been studied in multiple randomized trials. Yet, to date there has been no prior effort to pool data from multiple global trials to quantify the benefits we see from common treatment intensification strategies,Amar U. Kishan, MD, associate professor and vice-chair of clinical and translational research, and chief of the genitourinary oncology service for the department of radiation oncology at David Geffen School of Medicine at UCLA and UCLA Jonsson Comprehensive Cancer Center, told Healio.

These benefits include the addition of ADT to radiotherapy, prolonging the duration of ADT that follows radiotherapy , and extending the duration of ADT that may precede radiotherapy , Kishan added.

Methodology

Metastasis-free survival served as the studys primary outcome. Median follow-up was 11.4 years.

Key findings

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How Does Hormone Therapy Work Against Prostate Cancer

Early in their development, prostate cancers need androgens to grow. Hormone therapies, which are treatments that decrease androgen levels or block androgen action, can inhibit the growth of such prostate cancers, which are therefore called castration sensitive, androgen dependent, or androgen sensitive.

Most prostate cancers eventually stop responding to hormone therapy and become castration resistant. That is, they continue to grow even when androgen levels in the body are extremely low or undetectable. In the past, these tumors were also called hormone resistant, androgen independent, or hormone refractory however, these terms are rarely used now because the tumors are not truly independent of androgens for their growth. In fact, some newer hormone therapies have become available that can be used to treat tumors that have become castration resistant.

Do We Know Which Treatment Is Best For Prostate Cancer Brachytherapy Or External Beam Radiation

Its not a question of which type of radiation therapy is best in general, but rather which therapy is best for the patients specific disease and quality-of-life concerns. We want to use the most tailored, pinpointed radiation to treat the prostate tumor effectively while minimizing side effects. This can depend on the tumors size and stage as well as other patient characteristics and even a patients individual preferences.

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Hormonal Therapy On Its Own

Doctors do not usually advise having hormonal therapy instead of a prostatectomy or radiotherapy. Hormonal therapy alone cannot cure early or locally-advanced prostate cancer.

Depending on your general health and preferences, you may decide to have hormonal therapy on its own. For example, if you:

• are not well enough to have a prostatectomy or radiotherapy
• do not want to have a prostatectomy or radiotherapy
• are monitoring prostate cancer, for example having watchful waiting and the cancer starts to grow.

Hormonal therapy can slow down or stop the cancer cells growing for many years. It can also improve any symptoms. Not having surgery or radiotherapy means you avoid the side effects of these treatments. But hormonal therapy also causes side effects. It is important to talk to your doctor or nurse before you decide.

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

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Surgery For Prostate Cancer

If the cancer has not spread in your body, the whole prostate gland can be surgically removed. This is called a radical prostatectomy.

During the surgery, your surgeon will try to save the two bundles of nerves attached to the prostate that help you get erections. This is only possible if the cancer is not in or close to these nerves.

Sometimes lymph nodes are also removed during the surgery if the cancer has a higher risk of spreading.

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.

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Advising The Patient About Hormonal Therapy

Finally, Mark Moyad, MD, Director of Complementary and Preventive Medicine, University of Michigan, Department of Urology and Oncology, delivered an excellent discussion of the 10 steps he takes in advising patients about initiation of androgen deprivation therapy. Step 1 is to introduce patients to the common and less common side effects of androgen deprivation therapy . Step 2 is to introduce the patient to moderate, practical, and realistic dietary and lifestyle changes that promote general health during the androgen deprivation therapy. Dr. Moyad stated that recommendations for cardiovascular well-being extrapolate well to provide benefit to patients receiving androgen deprivation therapy. Step 3 is to emphasize that when it comes to over-the-counter supplements and other alternative approaches, less is more. He emphasized that some of these agents might have adverse effects on surgery or radiation therapy and that patients should discontinue these agents at least 1 week before definitive treatment. Step 4 is to remind patients that there might be dyslipidemia associated with androgen deprivation therapy patients should be told, know your lipid levels as well as your PSA.

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Hormone Therapy With Radiation

Hormone therapy is often given together with radiation therapy for localized disease .

Hormone therapy usually consists of a shot that lowers your testosterone, given every 1 to 6 months, depending on the formulation. Sometimes, it is prescribed as a daily pill that blocks testosterone from reaching the cancer cells. Clinical trials show a benefit in patients who receive hormonal treatment in combination with external beam radiation. Hormone therapy has been shown to improve cure rates of prostate cancer for men receiving radiation therapy and is part of the standard of care for men with certain types of intermediate-risk prostate cancer and nearly all high-risk prostate cancer. It is often given for intermediate-risk cancer for 4 to 6 months , and for 2 to 3 years in men with high-risk localized prostate cancer, although some doctors may recommend as little as 18 months of hormone therapy.

Hormone therapy should not be given to men with low-risk prostate cancer and is not a standalone treatment for localized prostate cancer in any risk category.

Want more information about a prostate cancer diagnosis and treatment options? Download or order a print copy of the Prostate Cancer Patient Guide.

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When To Consider Hormone Therapy

Hormone therapy is a treatment option for men with prostate cancer in any of the following situations:

• when cancer has metastasized beyond the prostate
• when cancer is confined to the prostate, but hormone therapy is used to boost the effectiveness of radiation therapy or to shrink the size of a tumor before brachytherapy
• when PSA begins to rise sometime after initial treatment with surgery or radiation therapy, indicating the cancer may have recurred.

Not all doctors agree on when to use hormone therapy, or how to administer it. Indeed, this is an area that requires a physician to exercise as much art as science in clinical practice. You should also be aware that side effects can be daunting, although most men tolerate treatment reasonably well .

Side Effects Of Androgen Deprivation Therapy

Since androgen deprivation treatment with LHRH analogues can also increase the risk of metabolic syndrome or diabetes mellitus, regular control of laboratory variables is required . Because of the two risks mentioned, the US Food and Drug Administration published a warning in 2010. This wasamong othersbased on a recommendation of the American Heart Association, the American Cancer Society, and the American Urological Association, and the support of the American Society for Radiation Oncology .

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Treating Prostate Cancer With Combined Hormonal

Androgens, the family of male sex hormones that includes testosterone, function as a fuel for growth in normal development. However, in some men they can also drive the progression of prostate cancer. Hormonal therapy treats prostate cancer by dramatically reducing levels of testosterone and other androgens.

Hormonal therapy is sometimes given in conjunction with external beam radiation to boost the effectiveness of treatment. Hormonal therapy may also be used to shrink the size of large prostate glands before brachytherapy takes place, to enable proper placement of the radioactive seeds.

Combination hormonal/radiation therapy is now a standard option for men with cancer that has extended beyond the prostate or whose cancer is considered high-risk based on other clinical findings, with studies showing that it reduces the risk of dying from prostate cancer and other causes more than with either treatment given alone..

Combination therapy can also be considered for men with localized prostate cancer in the intermediate-risk category. Whether men with low-risk prostate cancer would benefit from a hormonal therapyradiation combination is uncertain.

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Radiation Therapy Side Effects

Because the prostate is close to several vital structures, radiation therapy can disrupt normal urinary, bowel, and sexual functioning.Short-term ComplicationsYou may experience some temporary urinary symptoms, such as waking up in the night and needing to urinate, needing to urinate more often during â¦

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Diabetes And Heart Disease

Hormonal therapy may increase your risk for diabetes and heart disease. Maintain a healthy lifestyle to help reduce this risk.

• Dont smoke or use tobacco products. If you currently smoke, the Tobacco Treatment Program can help you quit. Your healthcare team will refer you to this program for support, or you can call for more information.
• Maintain or achieve a healthy body weight. If youd like to meet with a clinical dietitian nutritionist, call .
• Follow a healthy diet. Your diet should be high in fiber, low in fat, and low in concentrated sweets. For more information, read Nutrition and Prostate Cancer: Making Healthy Diet Decisions.
• Exercise regularly. Examples include brisk walking, jogging, biking, aerobics, and yard work. We recommend you exercise 30 minutes every day in addition to your daily routine. Even if you cant exercise every day, whatever you can do will be helpful.

Combined Androgen Blockade: Pro And Con

Pro:

Crawford ED, Eisenberger MA, McLeod DG, et al. A Controlled Trial of Leuprolide With and Without Flutamide in Prostatic Carcinoma. New England Journal of Medicine 1989 321:41924. PMID: 2503724.

Con:

Eisenberger MA, Blumenstein BA, Crawford ED, et al. Bilateral Orchiectomy With or Without Flutamide for Metastatic Prostate Cancer. New England Journal of Medicine 1998 339:103642. PMID: 9761805.

Two large meta-analyses that reviewed many studies comparing combined androgen blockade to monotherapy concluded that the combination offered only a small survival advantage and even that finding was inconsistent between the two analyses. One analysis, which reviewed 27 randomized studies involving 8,275 men, estimated that combined androgen blockade improved five-year survival by only 2% to 3%, at most. However, an advantage of only 2% to 3%, when applied to thousands of men undergoing treatment, translates into hundreds of lives extended obviously an important benefit to the men who gain months and even years of life as a result. That is why I use combined therapy for all of my patients who undergo hormone treatments.

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