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What Is Novel Hormone Therapy For Prostate Cancer

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Quality Of Life With Mcrpc

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

According to a review published in the British Medical Journal in October 2016, you may not experience pain or other symptoms at this stage of cancer, or you may experience many. Its different for everyone. So along with treating the cancer itself, be sure to talk to your doctors about any symptoms and side effects youre experiencing in order so that the right ways to alleviate them can be found. You should also ask your care team about options for palliative care.

Because it can be very stressful to have advanced prostate cancer, and tough to talk about what it all means for your future, the ASCO urges men to have an open and honest conversation with their care team. Discuss what youre worried about, and whats important to you. There are many ways to look for and get emotional support.

Additional reporting by Andrea Peirce

Heres What You Should Know About This Treatment Option

Men who get diagnosed with prostate cancer have several options to choose from for their next step. Many men with slow-growing, low-risk cancer follow active surveillance, a wait-and-see approach that monitors the cancer for changes.

But if the cancer shows higher risk or has already begun to spread, other treatments are recommended. There are two options: surgery to remove the prostate or radiation to destroy the cancer cells.

Studies comparing these two approaches demonstrate no advantage of one over the other with respect to cancer control. Your path will depend on factors like your current health, the specifics of your cancer, and personal preference. Yet for many men, radiation can be the better option.

Its much more precise than the traditional radiation used for other kinds of cancer, and research also has found that long-term quality of life is often better, with fewer adverse health effects compared to surgery, says Dr. Anthony DAmico, a radiation oncologist with Harvard-affiliated Dana-Farber Cancer Institute and Brigham and Womens Hospital.

There are two main ways to deliver radiation to the prostate: external beam radiation and brachytherapy.

Hormonal Agents Improve Survival In Mcspc But Novel Targets Are Needed For Further Drug Development

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Neeraj Agarwal, MD, discusses the role of docetaxel in the frontline setting, the emergence of novel hormonal agents in the paradigm, and efforts being made with combination regimens to potentially treat patients with resistant disease.

Although intensified therapy with hormonal agents like apalutamide , enzalutamide , and abiraterone acetate has improved survival in patients with metastatic castration- sensitive prostate cancer , new targets and novel approaches are necessary for those who progress on these agents, according to Neeraj Agarwal, MD.

By moving novel hormonal therapies to the up-front setting, we have seen a dramatic improvement in the overall survival of patients with mCSPC, said Agarwal. Novel hormonal therapies such as apalutamide, enzalutamide, and abiraterone are improving survival and delaying disease progression, without compromising quality of life this is great news for our patients.

Research efforts dedicated to improving outcomes include further examination of PARP inhibitors for patients with metastatic castration-resistant prostate cancer who harbor mutations in DNA repair genes, as well as novel immunotherapy combination regimens like cabozantinib plus atezolizumab , and pembrolizumab plus olaparib .

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Hormone Therapy For Prostate Cancer Increases The Risk Of Dying From Cardiovascular Disease

by Taylor & Francis

Hormone therapy for prostate cancer increases the risk of cardiovascular disease-related death especially in older men, according to a population study involving more than 13,000 patients.

The paper, published today in the peer-reviewed journal The Aging Male, found an elevated risk of death from cardiovascular disease for men with prostate cancer treated with hormone-lowering drugs compared with those who were not.

The highest risk was for coronary heart disease and stroke. The increased risks were apparent from the second year after cancer diagnosis and were more pronounced in older men.

“Hormone therapy is often used for patients with prostate cancer, but more research is now needed to gain a better understanding of the overall risks and benefits of this treatment,” says lead author Justinas Jonusas at the National Cancer Institute, Lithuania. “Our results suggest clinicians should consider risk reduction and mitigation strategies for cardiovascular disease when developing a treatment plan for men diagnosed with prostate cancer, particularly for older patients.”

After making suitable adjustments to the data, the researchers found:

The team also assessed the risk of death from several subtypes of cardiovascular disease, identifying there was a higher risk of dying specifically from stroke or coronary heart disease. These risks were 42% and 70% higher, respectively, in men treated with hormone therapy compared to those who were not.

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Surgery In Metastatic Disease

Treatment options for localized and metastatic prostate cancer and the ...

Physicians have suggested that the benefits seen from radiation to the prostate point to the benefits of local therapy, raising the question of whether radical prostatectomy might have the same results. Trials are ongoing, and at present the use of surgery should be considered investigational and conducted only within the context of a trial. However, transurethral resection is sometimes needed in men who develop obstruction secondary to local tumor growth. Bilateral orchiectomy can be used to produce androgen deprivation in patients with widely advanced and metastatic prostate cancer.

Since the introduction of LHRH agonist and antagonist therapies, surgical intervention has been practiced less often. An indication for immediate bilateral orchiectomy is spinal cord compression, because it avoids the potential flare response that can occur during the first 3 weeks of treatment with an LHRH agonist.

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The Facts About Hormonal Therapy For The Treatment Of Prostate Cancer

Hormonal Therapy in various forms may be prescribed for patients as part of their treatment at the Dattoli Cancer Center. Simply put, certain hormones have the ability to temporarily halt or slow the growth of prostate cancer, as well as to shrink the overall size of the prostate gland. Men with enlarged prostates can benefit by reducing the size of the gland, making it a smaller target for curative radiation therapy.

What Types Of Hormone Therapy Are Used For Prostate Cancer

Hormone therapy for prostate cancer can block the production or use of androgens . Currently available treatments can do so in several ways:

  • reducing androgen production by the testicles
  • blocking the action of androgens throughout the body
  • block androgen production throughout the body

Treatments that reduce androgen production by the testicles are the most commonly used hormone therapies for prostate cancer and the first type of hormone therapy that most men with prostate cancer receive. This form of hormone therapy includes:

Treatments that block the action of androgens in the body are typically used when ADT stops working. Such treatments include:

Treatments that block the production of androgens throughout the body include:

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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.

Could You Expand A Bit On The Stampede And Chaarted Trials How Did This Research Lead To The Development Of Newer Agents For Use As Intensified Therapy In This Setting

Changing the Treatment Story With Hormonal Therapy in Prostate Cancer

STAMPEDE is a very well-organized trial that is composed of multiple arms. Arms keep getting added and inefficient arms are also being removed. This is a big umbrella trial that is trying to determine whether docetaxel can be moved to the up-front setting. This trial includes not only patients with newly diagnosed disease, but those who have locally advanced disease, nonmetastatic disease, and lymph nodepositive disease.

The STAMPEDE population is more heterogeneous compared with that of the CHAARTED trial. The former showed that docetaxel improved OS in patients with metastatic prostate cancer. Again, it remains to be seen why this has not led to an uptake of docetaxel in a majority of patients in the United Kingdom. We are asking the same question with regard to the CHAARTED trial in the United States.

These trials were the first to show that intensified therapy in the mCSPC setting improves OS, and that has actually led to the advent of newer drugs such as apalutamide, enzalutamide, and abiraterone being used as intensified therapy in this setting. However, docetaxel use itself has not picked up in fact, its use is slowing down even more now. For example, I have not used docetaxel chemotherapy in more than a couple of patients in the past 6 or 7 months, especially in light of the coronavirus disease 2019 pandemic.

There is a huge reluctance for my patients to go with docetaxel if they an oral pill like apalutamide that doesnt require them to come in for a visit.

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Mutational And Genetic Testing In Mcrpc

All cancers, including prostate cancer, arise because of genetic mutations in cells. The first type mutations to be appreciated as causative in driving mCRPC were in genes involved in repair of damaged DNA. These mutations, often hereditary, were identified long ago as predisposing to the development of breast and ovarian cancers in women.

In prostate cancer, mutations in one of these DNA-repair genes are found mostly in late-stage prostate cancer in about 12% to 20% of patients. These mutations predict whether treatment with drugs known as PARP inhibitors might be effective. The FDA has already approved two drugs in this category: olaparib and rucaparib . New clinical guidelines now dictate testing for these mutations in tumors of mCRCP patients.

A recent study reported that men with deficiencies in one of 13 genes related to DNA damage repair had a higher response rate and a longer progression-free and overall survival when treated with the PARP inhibitor olaparib versus an anti-androgen treatment.

A new drug called berzosertib, an inhibitor of the DNA-repair protein ATR, has shown very promising results in a variety of cancers with relevant mutations, and is currently being tested in a trial for mCRPC in combination with chemotherapy.

How The Study Was Performed

During the study, scientists randomized 1,071 men with intermediate- or high-risk localized prostate cancer into four groups. One group received radiation and six months of an anti-testosterone drug called leuporelin, and the second group received radiation plus 18 months of leuporelin therapy. Two other groups were treated with the same regimens of either radiation plus six or 18 months of leuporelin therapy, along with another drug called zoledronic acid, which helps to limit skeletal pain and related complications should cancer spread to the bones. Study enrollment occurred between 2003 and 2007 at 23 treatment centers across New Zealand and Australia.

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Other Growth And Survival Pathways Contributing To Crpc

The Wnt/-catenin pathway is dysregulated in several types of cancer, including colorectal, liver and prostate cancer., In one study, abnormal -catenin expression was observed in 23% of tumor samples derived from radical prostatectomies and in 38% of CRPCs and was found to be related to high Gleason scores. -Catenin activates T-Cell factor/lymphoid enhancer factor-1 transcriptional activity and upregulates genes such as MYC, MMP7 and vascular endothelial growth factor. On the other hand, -catenin is an important component of cadherin cell adhesion complexes, which have a critical role in the development of EMT and CRPC. A functional relationship between Wnt/-catenin signaling and EMT has also been suggested. Among the Wnt/-catenin target genes are the transcriptional factors Twist-related proteins 1 and 2 and the zinc-finger protein SNAI2, which downregulate E-cadherin, potentially contributing to EMT.

Figure 2

Concerns When Selecting A Novel Hormonal Agent For Crpc

Hormone Therapy and Castration Resistance of Prostate Cancer Paperback ...

During a live virtual event, Alicia Morgans, MD, MPH, discussed the choice of novel hormonal agents to combine with androgen-deprivation therapy in nonmetastatic castrate-resistant prostate cancer.

CASE SUMMARY

In October 2016, a 57-year-old black man was referred to the urology department with a PSA of 6.8 ng/mL. His medical history included seizures that were controlled with oxcarbazepine. His mother and sister had a history of breast cancer, and his brother had a history of pancreatic cancer. A multiparametric MRI scan showed a 58 cc index lesion to his left prostate zone, and prostate imaging reporting and data system showed it to be 4/5, 1.8 cm. Three months later, he had a robotically assisted radical prostatectomy and extended lymph node dissection. Six weeks post operation, the patient had a PSA of 0.15 ng/mL and baseline serum testosterone of 420 ng/mL.

Androgen deprivation therapy was initiated with leuprolide depot at 45 mg. The patient returned in August 2019. His PSA doubling time was 8.6 months with a PSA of 1.2 ng/mL. In October 2019 he was restaged, and bone scans showed he was negative for metastatic disease with an ECOG performance score of 0. In October 2020, the patients PSA was 3.81 ng/mL.

A decision to add a novel hormonal agent was made. Which therapy would you most likely recommend?

Reference:

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Key Factors Associated With Chemotherapy Use: Chemotherapy Vs Adt Alone

Patients receiving chemotherapy were significantly younger than patients receiving ADT alone . Examining the key clinical reasons for treatment choice revealed that physicians prescribed chemotherapy vs ADT alone to significantly higher proportions of patients who were younger: , who had good performance status , whose top priority was OS , whose top priority was maximal PFS , for whom a rapid onset of action was required , who had high disease burden , or who had visceral metastases . All key clinical reasons for treatment choice for chemotherapy vs ADT alone are presented in Fig. .

What Are The Side Effects Of Hormone Therapy For Prostate Cancer

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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    Prediction Of Treatment Efficacy

    Predictive markers are useful for selecting optimal cancer treatment regimens. If the response to a previous drug can predict the response to subsequent drugs, this information can help in the selection of an effective treatment. However, validated markers for predicting the efficacy and safety of new therapeutics have not been identified. Response to previous treatments could not predict the efficacy of subsequent treatments., , , , , However, accumulating clinical experience allows us to identify subgroups of patients who will benefit from each treatment. For example, patients with rapid progression to CRPC had a reduced OS and poorer response to second-line hormone therapies, including AA and EZL. Simple classification based on serological values might be able to predict the response to AA. The neutrophil/lymphocyte ratio â¤5 and restricted metastatic spread to either bone or lymph nodes were each associated with better PSA response and OS for patients received AA. Androgen-AR-targeted drugs, such as AA or EZL, are likely to be preferable for men with asymptomatic or mildly symptomatic disease, slowly progressive disease, and low tumor volume with no visceral metastases, chemotherapy-naïve patients or patients that poorly tolerate chemotherapy. In contrast, for men with rapid progressing disease and a large volume tumor, low PSA levels for high tumor volume, visceral metastases or poor response to ADT, early treatment with chemotherapy might be indicated.

    Radiation Therapy: What It Is

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

    This therapy, also known as radiotherapy, is a cancer treatment procedure that uses high doses of radiation to kill cancerous cells and shrink the tumor as well. At low doses, this procedure is used as an x-ray.

    This therapy can be internal or external or both form. For external beam, a machine that is outside your body aims at the cancerous cells. For internal therapy, the radiations are placed inside your body inside or near the cancer.

    For radiotherapy for prostate cancer, high-energy rays are used to kill the cancer cells. This treatment procedure does not cause pain. However, it may result in various side effects that might cause pain and make you feel uncomfortable. The good thing is that there are numerous ways to manage radiotherapy side effects with the help of your radiation oncologist.

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    Prostate Cancer: Surgical Castration Linked To Fewer Adverse Events Than Chemical Castration

    Bilateral orchiectomy is as effective as treatment with gonadotropin-releasing hormone agonists in controlling prostate cancer and is associated with fewer clinically relevant adverse events, a population-based study has found.1

    Androgen-deprivation therapy with surgical or pharmacological castration has long been a mainstay of treatment for metastatic prostate cancer.2 However, due to concerns about cosmetic and psychological effects of surgical castration, that practice has been nearly eliminated in favor of medical castration.

    Given that these are 2 accepted alternative means to achieve testosterone blockade, it is important to understand the differences in side effects to properly counsel patients about their choices, said Quoc-Dien Trinh, MD, of Brigham and Womens Hospital and Dana-Farber Cancer Institute in Boston, MA, in an interview with Cancer Therapy Advisor.

    A total of 3295 men with metastatic prostate cancer 66 years or older were selected using the Surveillance, Epidemiology and End Results database between January 1995 and December 2009. The men either were treated with GnRHa or underwent bilateral orchiectomy .

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    Men who underwent surgical castration had significantly lower risks of experiencing any fractures, peripheral arterial disease, and cardiac-related complications than those who were treated with GnRHa.

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