Treatment Cost And Access To Agents In Latin America
Unequal access to life-prolonging agents and to the newer technologies for monitoring treatment is a major limitation to successfully treating patients with mCRPC across different countries in Latin America. Treatment cost is a primary factor for limiting access to cancer agents. This may in part be due to the rise in the incidence of chronic diseases including cancer, which now compete for resources previously predominantly allocated to treating infectious diseases .
Obtaining adequate financing for cancer treatment is a challenge for many Latin American countries. The budget percentage spent for health in Latin America is generally lower than that of developed countries, although there are clear disparities between countries in Latin America for example, Argentina spends 8.1% of its gross domestic product on health, whereas Brazil, the most populous country of the region, spends only 6.3% . In the majority of these cases, however, health expenditures are concentrated in the private sector. For example in Mexico in 2008, of the total spent on health, 52% was for the private sector, which covers only 5% of the entire population .
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.
Treatments For Metastatic Castration
Castration-sensitive prostate cancer is cancer that is being controlled by keeping the testosterone level as low as would be expected if the testicles were removed . Metastatic prostate cancer is prostate cancer that has spread to other parts of the body.
The goal of treatment is to help you live longer and try to improve your quality of life. Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan.
Treatment options for metastatic castration-sensitive prostate cancer may include a combination of the following:
- hormone therapy
- watchful waiting
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An Evolving Standard Of Care
Hormone-sensitive prostate cancer means a patients tumors are still largely being fueled by male sex hormones called androgens. For many years, metastatic hormone-sensitive prostate cancer was treated with ADT alone, which blocks the production of androgens by the testicles.
In 2014, a large clinical trial showed that adding the chemotherapy drug docetaxel to ADT improved survival in men with metastatic hormone-sensitive prostate cancer. Since then, this combination has become the standard of care for this group of patients.
More recently, studies have shown that adding other drugs that block the production or binding of androgensincluding abiraterone , enzalutamide , and apalutamide to ADT also helps people with metastatic hormone-sensitive prostate cancer live longer. In a trial combining apalutamide with ADT, for example, approximately 82% of men were still alive after 2 years compared with 74% of men treated with ADT alone.
Several clinical trials were then launched to see if combining any of these drugs with ADT and docetaxel could build on those survival gains. Results of those studies, however, have been mixed, with one showing an improvement in survival without the disease progressing and another finding no increase in overall survival.
Possible Future Treatment Strategy As Per The Clinical And Biological Characteristics
The treatment strategies should be determined as per cancer and patient characteristics as well as patient preference. We showed the possible treatment strategy for patients with mCSPC as per patient subgroups . Group 1: elderly and/or fragile patients with very limited life expectancy ADT alone or best supportive care. Group 2-a: patients with low-volume, low-risk disease, favorable response to ADT, and life expectancy < 10 y ADT alone, because long-term OS, about 10 years, is expected with ADT alone in this patient group.33 Adverse events caused by upfront combination therapies may exceed their efficacy in those patients. Group 2-b: patients with the same cancer characteristics as group 2-a patients and having longer life expectancy upfront combination therapies using docetaxel or ARPIs, with or without prostatectomy or EBRT to the prostate together with ADT. Metastases-directed radiotherapy may be also indicated. Complete eradication of cancer and cure may be anticipated with these aggressive combination treatments in these patients. Group 3: patients with high-volume, high-risk, or unfavorable response to ADT upfront combination therapies using docetaxel or ARPIs. Group 4: patients carrying DDR gene mutations poly polymerase inhibitors or platinum-based chemotherapy. The prognostic and predictive biomarker-based decision will enable optimal personalized treatment.
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Survival Improving In Metastatic Castration
Overall survival improved among men with metastatic castration-sensitive prostate cancer after the introduction of docetaxel and novel hormonal therapies for treating this disease state, according to study findings presented at the European Society for Medical Oncology 2022 Congress in Paris, France.
Daniel J. George, MD, of Duke University Medical Center in Durham, North Carolina, and colleagues studied 39,292 men with mCSPC . The investigators divided patients into 3 cohorts of patients who received first-line treatment for mCSPC: those treated during 2010-2011 2012-2014 and 2015-2018 and 2015-2019 to capture the effects of the introduction of NHT and docetaxel for treating mCSPC.
Compared with Medicare and VA patients treated during 2010-2011, Medicare patients treated during 2015-2018 and VA patients treated during 2015-2019 had a significant 12% and 15% lower risk for death, respectively, the investigators reported in a poster presentation. OS survival did not improve during 2012-2014 compared with 2010-2011.
Although treatment intensification with NHT or doctaxel for mCSPC is standard of care, the investigators found that as of 2018-2019, less than one-third of men with mCSPC received this regimen as first-line therapy. The underutilization of these agents in mCSPC suggests that further OS improvements may be possible, the authors concluded.
Disclosures: The study was funded by Pfizer and Astellas Pharma.
Reference
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.
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Metastatic Hormone 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.
Definitive Treatment Is Beneficial Only In Patients With Low
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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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 CancerNetwork® 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.
Fda Approves Enzalutamide For Metastatic Castration
December 16, 2019 Today the U.S. Food and Drug Administration approved a new use for enzalutamide for the treatment of metastatic hormone-sensitive prostate cancer . Enzalutamide has previously been FDA-approved for the treatment of metastatic castration-resistant prostate cancer and non-metastatic castration-resistant prostate cancer .
PCF funded the initial synthesis of enzalutamide at UCLA by chemist Michael Jung, PhD, in collaboration with prostate cancer physician-scientist Charles Sawyers, MD .
mHSPC refers to men whose prostate cancer has spread to areas of the body outside of the prostate itself, and who are responsive to testosterone-lowering agents. This may refer to men who have had prior surgery or radiation and recurred, or men who were initially diagnosed with disease that was already metastatic . Patients who are hormone-sensitive may have previously received androgen deprivation therapy for a certain amount of time, but their cancer has not yet developed resistance to ADT.
This approval is based on results from the randomized phase 3 ARCHES clinical trial, which was presented at the 2019 Genitourinary Cancers Symposium held in February, and published in the prestigious medical journal, the Journal of Clinical Oncology.
More information on this approval can be found here.
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Understanding Advanced Prostate Cancer
There are different forms of advanced prostate cancer. Two types are metastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer .
- Metastatic castration-resistant prostate cancer is a form of prostate cancer that is resistant to medical or surgical treatments that lower testosterone, and has spread to other parts of the body
- Metastatic castration-sensitive prostate cancer is a form of prostate cancer that still responds to medical or surgical treatments that lower testosterone, and has spread to other parts of the body. Certain men may be considered to have metastatic high-risk castration-sensitive prostate cancer. Talk to your doctor about what this may mean for you
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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Improved Survival At 4 Years
In the ARASENS trial, nearly 1,300 participants were randomly assigned to receive darolutamide or a placebo . All participants received ADT within 12 weeks before randomization and six cycles of docetaxel starting within 6 weeks after randomization.
After 4 years, about 63% of patients who received darolutamide were still alive compared with about 50% of patients who received placebo. The group that received darolutamide lived longer even though most participants in the placebo group received other commonly used treatments, including abiraterone and enzalutamide, during follow-up.
Darolutamide resulted in other improvements as well. For example, among those treated with darolutamide, the time for their cancers to become resistant to hormone-suppressing therapies was longer, as was the time until the pain caused by their cancer got worse.
The frequency of serious side effectswhich included fatigue, falls, fractures, and cardiac issueswas similar in the two groups. Roughly two-thirds of the patients in both groups experienced serious side effects, most of which occurred when darolutamide were given at the same time as docetaxel.
More Options Lead To More Questions
Elisabeth Heath, M.D., director of prostate cancer research at Karmanos Cancer Institute in Detroit, agreed that the ARASENS results should have an immediate impact on how this form of the disease is treated.
Speaking at the ASCO symposium, Dr. Heath, who was not involved in the study, highlighted an important difference between ARASENS and other trials that tested androgen receptorblocking drugs in men with this form of prostate cancer. In those other trials, she explained, some participants received docetaxel prior to treatment with the androgen receptorblocking drugs rather than at the same time.
Based on the ARASENS results, Dr. Heath said, giving all three treatments simultaneously looks to be the preferred option for some patients.
Dr. Karzai noted that despite there being multiple options to treat metastatic hormone-sensitive prostate cancer, many questions remain. We don’t have guidelines on who should start with what drug and whether one drug is better than another for a patient, she said.
She also pointed out that more research is needed on how the order in which the drugs are given impact their effectiveness and the frequency of side effects.
Additionally, she said, the survival improvement in the ARASENS trial was seen in patients whose cancer had spread in multiple areas beyond the prostate .
We dont know if people with lower-volume benefit from as much as the patients with higher-volume disease do, she said.
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Balance Of Efficacy And Toxicity
Serious adverse events were observed in 30%-60% of patients receiving combination therapies.911,23,25 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.