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Castrate Sensitive Metastatic Prostate Cancer

If Treatment Does Not Work

TITAN Phase 3 Trial with Apalutamide in Metastatic Castration Sensitive Prostate Cancer

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.

Balance Of Efficacy And Toxicity

Serious adverse events were observed in 30%-60% of patients receiving combination therapies.,23,25 The toxicity may exceed the benefits in some patients. Increased medical expense with combination therapies is also an issue.

Some metastatic patients are also shown to achieve long-term survival with ADT alone. For example, patients with low-volume and low-risk mCSPC who achieved PSA 2 ng/mL at 3 mon after ADT commencement had a considerably long OS of 112 mon with ADT with or without first-generation antiandrogens.33 It is very likely that upfront combination therapy using docetaxel and ARPIs would be excessive for these patients. The profile of adverse events and medical cost are different among agents. For example, docetaxel is cheaper than ARPIs, but it is associated with neutropenia and peripheral neuropathy.5 ENZ increases the risk of fatigue, hypertension, cardiovascular event, and seizure.9,10,34 Abi is associated with hypertension, cardiovascular events, and hypokalemia.23,34 Rash is relatively common adverse event of APA.11 Therefore, treatments must be tailored according to the individual patients profile, comorbidities and preferences, and it is crucial to choose the appropriate treatments for each patient while avoiding unnecessary overtreatment. All-comers therapeutic approaches may not be used anymore in clinical practice.

Treatment By Stage Of Prostate Cancer

Different treatments may be recommended for each stage of prostate cancer. Your doctor will work with you to develop a specific treatment plan based on the cancers stage and other factors. Detailed descriptions of each type of treatment are provided earlier on this same page. Clinical trials may also be a treatment option for each stage.

Early-stage prostate cancer

Early-stage prostate cancer usually grows very slowly and may take years to cause any symptoms or other health problems, if it ever does at all. As a result, active surveillance or watchful waiting may be recommended. Radiation therapy or surgery may also be suggested, as well as treatment in clinical trials. For those with a higher Gleason score, the cancer may be faster growing, so radical prostatectomy and radiation therapy are often recommended. Your doctor will consider your age and general health before recommending a treatment plan.

ASCO, the American Urological Association, American Society of Radiation Oncology, and the Society of Urologic Oncology recommend that patients with high-risk early-stage prostate cancer that has not spread to other areas of the body should receive radical prostatectomy or radiation therapy with hormonal therapy as standard treatment options.

Locally advanced prostate cancer

Watchful waiting may be considered for older adults who are not expected to live for a long time and whose cancer is not causing symptoms or for those who have another, more serious illness.

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Patient Selection And Study Design

  • ADT + abiraterone : Patients with claims for abiraterone within 4 months after or within 30 days prior to ADT initiation were classified as ADT + abiraterone.
  • ADT + docetaxel : Patients with claims for docetaxel within 4 months after or within 30 days prior to ADT initiation were classified as ADT + docetaxel.
  • ADT + NSAA : Patients prescribed NSAAs for 3 months after the initial ADT date were classified as ADT + NSAA. Patients treated with NSAA for < 3 months were classified as ADT-only.
  • ADT-only : Patients with mCSPC who received ADT-only were classified as ADT-only.

The index date was defined as the start of ADT, abiraterone, docetaxel, or NSAA, whichever occurred first.

Unmet Needs For Mcspc

Metastatic Castrate Resistant Prostate Cancer Management

There are a variety of unmet needs to understand how to best manage each individual patient, Choudhury acknowledged. These include determining optimal treatment for patients with localized disease the role of androgen receptor therapy intensification for patients treated in the neoadjuvant or adjuvant setting using molecular diagnostics to determine if a patient should escalate or deescalate treatment and who should receive salvage radiation and when it should be initiated.Of note, Choudhury mentioned that the US Preventive Services Task Force recommendations in 2012 played a key role in changing the diagnosis and management of patients with mCSPC and specifically cited decreased prostate-specific antigen screenings in this setting.7Where novel imaging comes into play is unclear, Choudhury explained. Should all patients who have a PSA less than 0.2 get a /PET scan as part of the radiation planning? I dont think that answer has been developed yet.

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From Personalized To All

A systematic review and meta-analyses of the aggregate data of the CHAARTED, GETUG-AFU15, and STAMPEDE trials indicated that the upfront use of docetaxel showed better OS in patients with mCSPC than in those with ADT alone .24 As per the STAMPEDE trial, upfront docetaxel improved the OS irrespective of the metastatic tumor burden .25 For low-volume patients, the median OS was 93.2 mon and 76.7 mon for upfront docetaxel and ADT alone, respectively . This HR was consistent with that in high-volume patients , suggesting that upfront docetaxel would be beneficial for all patients with mCSPC, irrespective of the metastatic burden, and this treatment may be for all-comers.

These recent clinical trials suggest that early combination therapies are consistently associated with better outcomes than ADT alone, irrespective of the tumor burden and risk category. Thus, recent clinical guidelines recommend a combination of docetaxel or ARPIs with ADT as first-line therapy for all patients with mCSPC.13,14 The era of ADT alone may end and upfront combination therapies are becoming a standard of care as the initial treatment for all-comers with mCSPC.

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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Study Design And Participants

CheckMate 9KD is a non-randomized, open-label, multicohort, phase 2 trial of nivolumab combined with rucaparib , docetaxel , or enzalutamide for mCRPC. Methods for the overall study and specific to cohort B have previously been described. In brief, the CheckMate 9KD study population comprises adult patients with histological confirmation of adenocarcinoma of the prostate with radiologic evidence of stage IV disease , ongoing androgen deprivation therapy or bilateral orchiectomy , and documented progressive disease per Prostate Cancer Clinical Trials Working Group 3 criteria. Eligible patients were also required to have an Eastern Cooperative Oncology Group performance status of 0 or 1 and sufficient tumor tissue obtained within 5 years before enrollment from a metastatic or primary tumor lesion not previously irradiated. Exclusion criteria included active brain metastases, conditions requiring systemic treatment with corticosteroids or other immunosuppressive medications within 14 days of start of study treatment, and prior therapy specifically targeting T-cell costimulation or immune checkpoint pathways.

Metastatic Hormone Sensitive Prostate Cancer

Dr. Yu on Treatment Intensification in Metastatic Castration-Sensitive Prostate Cancer

This form of prostate cancer can be an initial diagnosis but more often refers to cases where surgeries or other initial treatments to remove tumors from the prostate havent succeeded in stopping its progression.

Notably, too, these cases are defined by metastasis, meaning it has started to spread to other structures in the body, such as bones or the lymph nodes. However, the development of castration resistance is part of the eventual and expected progression of the diseaseeven while on ADT.

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Clinical Research Supporting Treatment Options For Mcspc

Further, triplet therapieswith abiraterone plus docetaxel/ADT in the PEACE-1 trial 5 and darolutamide plus docetaxel/ADT in the ARASENS trial 6have shown a benefit over docetaxel plus ADT alone for patients with mCSPC.Its clear from the studies presented that even patients with low-volume metastatic disease benefit from intensification of treatment, Choudhury explained. Quality-of-life data from these studies also suggest that patients will benefit from earlier treatment with these agents.Choudhury further explained the QOL benefits that emerge from intensification of therapy.Even though there are clearly decrease adverse effects associated with the cancer itself, Choudhury said. The QOL with these agents is superior patients who are treated with ADT alone.Overall, Choudhury emphasized the importance of starting therapy earlier in the process. Unless a contraindication exists for patients, he suggested that the survival and QOL data support the early integration of intensified therapy into mCSPC treatment.Theres no cancer-related or QOL reason to not consider these agents earlier in the process, Choudhury said.

First Parp Inhibitor To Demonstrate Clinical Benefit In Combination With A New Hormonal Agent Irrespective Of Homologous Recombination Repair Gene Mutations

AstraZenecas supplemental New Drug Application for Lynparza in combination with abiraterone and prednisone or prednisolone has been accepted and granted Priority Review in the US for the treatment of adult patients with metastatic castration-resistant prostate cancer .

Lynparza is being jointly developed and commercialised by AstraZeneca and MSD.

The Food and Drug Administration grants Priority Review to applications for medicines that offer significant advantages over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the fourth quarter of 2022.

In the US, prostate cancer is the second most common cancer in male patients and is projected to cause approximately 35,000 deaths in 2022.2 Overall survival for patients with mCRPC is approximately three years in clinical trial settings, and even shorter in the real world.3-6 Approximately half of patients with mCRPC may receive only one line of active treatment, with diminishing benefit of subsequent therapies.6-11

The sNDA was based on results from the PROpel Phase III trial presented at the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium and later published in NEJM Evidence.

Notes

For more information about the trial please visit ClinicalTrials.gov.

Contacts

References

Adrian Kemp

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Remission And The Chance Of Recurrence

A remission is when cancer cannot be detected in the body and there are no symptoms. This may also be called having no evidence of disease or NED.

A remission can be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. Although there are treatments to help prevent a recurrence, such as hormonal therapy and radiation therapy, it is important to talk with your doctor about the possibility of the cancer returning. There are tools your doctor can use, called nomograms, to estimate someone’s risk of recurrence. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the cancer does return. Learn more about coping with the fear of recurrence.

In general, following surgery or radiation therapy, the PSA level in the blood usually drops. If the PSA level starts to rise again, it may be a sign that the cancer has come back. If the cancer returns after the original treatment, it is called recurrent cancer.

When this occurs, a new cycle of testing will begin again to learn as much as possible about the recurrence, including where the recurrence is located. The cancer may come back in the prostate , in the tissues or lymph nodes near the prostate , or in another part of the body, such as the bones, lungs, or liver . Sometimes the doctor cannot find a tumor even though the PSA level has increased. This is known as a PSA recurrence or biochemical recurrence.

Definitive Treatment Is Beneficial Only In Patients With Low

TITAN trials demonstrates significantly Improved Overall Survival and ...

Not only systemic pharmacotherapy, but radiation to the prostate also improves OS in low-volume disease. The recent high-quality RCTs, STAMPEDE29 and Hormonal Therapy Versus Hormonal Therapy Plus Local External Radiation Therapy in Patients With Primary Diagnosed Metastasized Prostate Cancer ,30 concluded that adding radiation therapy to the prostate in mCSPC patients receiving ADT did not further improve their OS, the primary endpoint. In contrast, subgroup analyses by metastatic burden in the STAMPEDE trial showed OS benefit for patients with low-volume disease . The HORRAD trial also showed a similar trend without statistical significance in patients with < 5 metastatic lesions. Meta-analysis of 2 RCTs that involved 2493 patients suggested that ADT plus EBRT to the prostate was associated with improved OS as compared to ADT alone in men with low-volume metastatic burden however, this result was not observed in those with high-volume disease .28 Prostatectomy may also improve the oncologic outcomes in patients with oligometastatic prostate cancer.31 The definitive treatments, either radiation or prostatectomy, may be associated with survival benefit in patients with low metastatic burden. The results of several ongoing clinical trials on the benefit of prostatectomy and radiation to the prostate are expected to provide more information on this subject.32

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Bone Marrow Involvement In Patients With Metastatic Castration Sensitive Prostate Cancer

  • Roles Conceptualization, Data curation, Validation, Writing original draft, Writing review & editing

    Affiliation Department of Surgery, King Hussein Cancer Center, Amman, Jordan

  • Roles Data curation, Supervision, Writing original draft

    Affiliation Department of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan

  • Roles Conceptualization, Formal analysis, Writing review & editing

    Affiliation Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan

  • Roles Conceptualization, Methodology, Visualization, Writing original draft, Writing review & editing

    Affiliation Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon

A Titan Step Forward: Apalutamide For Metastatic Castration

Daniel Hyuck-Min Kwon1,2, Terence Friedlander1,2

1 Department of Medicine, Division of Hematology and Oncology, 2 The Helen Diller Family Comprehensive Cancer Center, University of California San Francisco , , USA

Correspondence to:

Provenance: This is an article commissioned by the Section Editor Weijun Jiang .

Submitted Aug 10, 2019. Accepted for publication Aug 30, 2019.

doi: 10.21037/atm.2019.09.21

Metastatic prostate cancer, which presents as either de novo or as a recurrence following definitive therapy for localized disease, has historically been treated with androgen deprivation therapy alone. Although 90% of men initially respond to ADT, almost all eventually become castration-resistant and develop progression of their disease. Over the past several years, several landmark randomized clinical trials have led to the use of docetaxel, a taxane chemotherapy administered intravenously every 3 weeks for 6 cycles, or abiraterone, an orally administered inhibitor of CYP17A1 given together with a low-dose glucocorticoid, in combination with ADT as standard of care among men with metastatic castration-sensitive prostate cancer . The median overall survival with these therapies is upwards of 53 months, depending on the disease stage, extent, and burden of the study population.

Table 1Table 2

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Treatment Options In Metastatic Castration

In this program Atish D. Choudhury, MD, PhD, discusses recent updates on long-term safety and efficacy data in patients with metastatic castration-sensitive prostate cancer and the importance of patient communication and quality of life while on treatment.

During a Clinical Consult presentation, Atish D. Choudhury, MD, PhD, spoke with CancerNetworkĀ® about long-term safety and efficacy data for agents related to metastatic castration-sensitive prostate cancer as well as several unmet needs for this patient population.We have been seeing an increase in men who are presenting initially with metastatic disease, explained Choudhury, co-director of the Prostate Cancer Center at the Dana-Farber/Brigham and Womens Cancer Center and assistant professor of medicine at Harvard Medical School. It means that more men are presenting in this space and were getting some increasing data around how to optimally manage them.Choudhury expanded on those unmet needs for patients with mCSPC and the various treatment options that are considered for each individual patient.

De Novo Metastatic Castration Sensitive Prostate Cancer In A 73

Update: FDA Approves Apalutamide (Erleada) for Metastatic Castration-Sensitive Prostate Cancer

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