Effectiveness of Tai Chi vs Cognitive Behavioural Therapy for Insomnia in Middle-Aged and Older Adults
November 27, 2025
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Background
Castration-resistant prostate cancer (CRPC) is a stage of prostate cancer that progresses despite androgen deprivation therapy (ADT), which is the primary treatment for advanced prostate cancer. It is also known as hormone-refractory or androgen-independent prostate cancer. CRPC is characterized by the continued growth and spread of prostate cancer cells even without testosterone, the primary fuel for prostate cancer growth.
The development of CRPC is a complex process involving various molecular and cellular changes in the tumor cells. It is thought to arise from the selection and survival of cancer cells that have acquired mechanisms to bypass the androgen signaling pathway. These mechanisms include increased androgen receptor expression, activation of alternative signaling pathways, genetic alterations, and development of castration-resistant clones.
CRPC is associated with poor prognosis and represents a significant challenge in the management of advanced prostate cancer. It often leads to metastatic disease, spreading to other organs such as the bones, lymph nodes, or distant sites.
Epidemiology
Incidence: The incidence of CRPC varies depending on the stage of prostate cancer and the population studied. It typically occurs in men who have received androgen deprivation therapy (ADT) for advanced prostate cancer.
Prevalence: CRPC accounts for a significant proportion of advanced prostate cancer cases. As prostate cancer is one of the most common cancers in men, the prevalence of CRPC is substantial.
Age: The risk of developing CRPC increases with age, and it is more commonly diagnosed in older men. However, it can occur in men of any age who have received ADT.
Racial and Ethnic Disparities: Studies have shown variations in the incidence and outcomes of CRPC among different racial and ethnic groups. African American men have been found to have a higher incidence and poorer prognosis compared to other populations.
Risk Factors: The development of CRPC includes advanced age, high initial prostate-specific antigen (PSA) levels, high Gleason score, and extent of disease at the time of diagnosis.
Anatomy
Pathophysiology
Androgen Receptor Signalling: The development and progression of prostate cancer are driven by androgen receptor signalling, which is stimulated by androgens such as testosterone. In CRPC, the cancer cells find alternative mechanisms to activate androgen receptor signalling despite low levels of circulating androgens.
Androgen Deprivation Therapy (ADT): ADT is a standard treatment for advanced prostate cancer that aims to lower androgen levels. Initially, ADT is effective in suppressing tumor growth, but over time, prostate cancer cells can adapt and become resistant to ADT, leading to the development of CRPC.
Androgen Receptor Alterations: CRPC is characterized by alterations in the androgen receptor (AR) pathway. These alterations can include amplification of the AR gene, mutations in the AR gene, or increased expression of co-activators that enhance AR signalling. These changes allow the cancer cells to bypass the need for circulating androgens and remain active even in low androgen environments.
Intratumoral Androgen Production: Another mechanism contributing to CRPC is the intratumoral production of androgens. Prostate cancer cells can synthesize androgens locally, allowing them to sustain androgen receptor signalling despite systemic androgen deprivation.
Activation of Alternative Signalling Pathways: In CRPC, cancer cells can activate alternative signalling pathways, such as the PI3K/AKT/mTOR pathway or the WNT/β-catenin pathway, which promote cell survival and growth independently of androgen receptor signalling.
Etiology
Continued Androgen Production: In some cases of CRPC, the tumor cells develop the ability to produce androgens locally within the tumor microenvironment. This can occur through increased expression of enzymes involved in androgen synthesis, allowing the cancer cells to maintain androgen signalling despite systemic androgen deprivation.
Androgen Receptor Coactivators: Overexpression of coactivators that enhance AR signalling can contribute to the development of CRPC. These coactivators can facilitate AR activation even in the presence of low androgen levels.
Genetic Alterations: Genetic mutations and alterations in CRPC can affect various genes involved in cell cycle regulation, DNA repair mechanisms, and tumor suppressor pathways. These alterations contribute to the development of resistance to therapies and promote tumor growth.
Tumor Microenvironment: The tumor microenvironment plays a crucial role in the progression of CRPC. Interactions between cancer cells and surrounding stromal cells, immune cells, and cytokines contribute to the development of resistance mechanisms and promote tumor growth and metastasis.
Genetics
Prognostic Factors
PSA Doubling Time: PSA doubling time, which measures how quickly the prostate-specific antigen (PSA) levels double, is a strong prognostic factor in CRPC. A shorter PSA doubling time indicates more aggressive disease and poorer prognosis.
Gleason Score: The Gleason score, which is based on the histological assessment of prostate cancer cells, is a well-established prognostic factor for both localized and advanced prostate cancer. Higher Gleason scores (8-10) are associated with a higher risk of disease progression and poorer outcomes.
Disease Stage: The stage of CRPC at diagnosis is an important prognostic factor. Metastatic disease at the time of CRPC diagnosis indicates a higher disease burden and poorer prognosis compared to localized disease.
Performance Status: The performance status of a patient, often assessed using the Eastern Cooperative Oncology Group (ECOG) performance status scale, is a prognostic factor in CRPC. A better performance status indicates a higher level of physical functioning and is associated with improved outcomes.
Presence of Metastases: The presence and extent of metastases in CRPC, especially to vital organs such as the liver or lungs, are significant prognostic factors. Patients with extensive metastatic disease have a poorer prognosis compared to those with localized or limited metastases.
Serum LDH and ALP Levels: Elevated levels of serum lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) are associated with a higher tumor burden and poorer prognosis in CRPC. These biomarkers reflect disease activity and can help predict treatment response and survival.
Clinical History
Age Group:
Castration-resistant prostate cancer (CRPC) typically occurs in older men. The median age at diagnosis of CRPC is around 70 years, although it can be diagnosed in men of various age groups.
Physical Examination
Digital Rectal Examination (DRE):
Genitourinary Examination:
Abdominal Examination:
Neurological Examination:
Bone Examination:
Age group
Associated comorbidity
Patients with CRPC may have associated comorbidities such as cardiovascular disease, diabetes, hypertension, or other chronic conditions.
These comorbidities can impact treatment decisions and overall management.
Associated activity
Activity Level:
The activity level of patients with CRPC can vary depending on their overall health and disease progression. Some patients may experience fatigue or reduced energy levels due to the advanced stage of the disease, while others may maintain a normal activity level.
Acuity of presentation
The acuity of presentation in CRPC can vary depending on the disease course. Some patients may have a gradual progression of symptoms and biochemical markers, while others may experience a more rapid deterioration in their condition. Acute complications, such as spinal cord compression or skeletal-related events, can also occur in advanced cases.
Differential Diagnoses
Benign Prostatic Hyperplasia (BPH):
Prostatitis:
Metastatic Cancer:
Prostate Intraepithelial Neoplasia (PIN):
Prostate Lymphoma:
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Castration-Resistant Prostate Cancer (CRPC) involves a variety of therapeutic options aimed at slowing disease progression, relieving symptoms, and improving overall survival. The specific treatment approach depends on various factors such as disease extent, symptoms, prior treatments, patient preferences, and overall health.
Androgen Receptor (AR)-Targeted Therapies:
enzalutamide: An oral AR antagonist that inhibits AR signaling and can improve overall survival and delay disease progression.
abiraterone acetate: An oral medication that blocks the synthesis of androgens, including testosterone, and can improve survival when combined with prednisone.
apalutamide: Another oral AR antagonist that has shown efficacy in delaying disease progression and improving survival.
Chemotherapy:
docetaxel: A chemotherapy drug that can improve survival and quality of life when combined with prednisone. It is typically used in patients who have progressed after initial hormone therapy.
cabazitaxel: Another chemotherapy agent approved for use in CRPC after docetaxel treatment.
Immunotherapy:
Sipuleucel-T: A cellular immunotherapy that stimulates the patient’s immune system to target prostate cancer cells. It is typically used in asymptomatic or minimally symptomatic patients with metastatic CRPC.
Targeted Therapies:
Radium-223: A targeted alpha therapy that delivers radiation to bone metastases, providing palliative benefit and improving survival in patients with bone-dominant disease.
PARP inhibitors: Olaparib and rucaparib are approved for patients with certain genetic mutations, such as BRCA1/2, and can be effective in slowing disease progression.
Radiopharmaceuticals:
PSMA-targeted radioligand therapy: Radiopharmaceuticals such as lutetium-177 PSMA-617 or actinium-225 PSMA-617 can target prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation to tumors.
Other Therapies:
Palliative care: Supportive care to manage symptoms, improve quality of life, and address psychosocial needs.
Clinical trials: Participation in clinical trials investigating new treatments or combinations.
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
diet-and-nutrition
Plant-Based Foods: Include a variety of plant-based foods in diet, such as fruits, vegetables, whole grains, nuts, and seeds. These are rich in antioxidants, vitamins, minerals, and fiber, which can support overall health.
Healthy Fats: Incorporate healthy fats into your diet, such as olive oil, avocados, nuts, and seeds. These fats provide essential nutrients and may have anti-inflammatory properties.
Limit Saturated and Trans Fats: Reduce the intake of saturated fats found in red meat, full-fat dairy products, and fried foods. Minimize or avoid trans fats found in processed and packaged foods, as they can increase inflammation and negatively impact overall health.
Omega-3 Fatty Acids: Include omega-3 fatty acids in your diet, which can be found in fatty fish (such as salmon, sardines, and trout), walnuts, chia seeds, and flaxseeds. Omega-3 fatty acids have been associated with potential health benefits, including anti-inflammatory effects.
exercise-and-physical-activity
Aerobic Exercise: Engage in regular aerobic exercises such as walking, cycling, swimming, or low-impact aerobics. Aim for at least 150 minutes or 75 minutes of aerobic activity, or a combination of both.
Strength Training: Incorporate strength training exercises to maintain or improve muscle strength and endurance. Resistance exercises using weights, resistance bands, or bodyweight can help preserve muscle mass and enhance overall physical function.
Flexibility and Stretching: Include flexibility exercises to improve joint mobility and flexibility. Stretching exercises, yoga, or tai chi can help maintain or improve flexibility and balance.
Balance and Stability Training:
consider incorporating balance and stability exercises to reduce the risk of falls and improve overall stability. These exercises can include standing on one leg, heel-to-toe walk, or exercises that challenge balance.
stress-management
Relaxation Techniques: deep breathing exercises, progressive muscle relaxation, guided imagery, or meditation. These techniques can help reduce stress, promote relaxation, and improve overall well-being.
Mindfulness-Based Stress Reduction (MBSR): MBSR programs involve training in mindfulness meditation and can help individuals develop skills to manage stress and enhance coping mechanisms. Consider participating in MBSR programs offered by qualified instructors or using mobile apps and online resources for guided mindfulness practices.
Support Systems: Maintain a strong support network of family, friends, or support groups. Sharing your experiences, concerns, and emotions with others who are going through similar challenges can provide emotional support and help alleviate stress.
Counselling or Therapy: Consider seeking professional counselling or therapy to help manage stress and address any emotional concerns associated with CRPC. Individual counselling, support groups, or couples counselling can provide a safe space to discuss emotions, fears, and challenges related to the condition.
supportive-care
Symptom Management: Addressing and managing symptoms associated with CRPC, such as pain, fatigue, nausea, and urinary or bowel problems, is essential. This may involve the use of medications, lifestyle modifications, physical therapy, and other interventions to alleviate symptoms and improve comfort.
Palliative Care: It is an important component of supportive care for CRPC. It focuses on relieving symptoms, managing pain, and improving quality of life. Palliative care teams work closely with patients and their families to address physical, emotional, and spiritual needs throughout the course of the disease.
Psychological and Emotional Support: The emotional impact of CRPC can be significant. Providing psychological support, counselling, and access to support groups can help individuals cope with the emotional challenges associated with the condition. Psychosocial support can also extend to family members and caregivers.
Nutritional Support: Proper nutrition is essential for individuals with CRPC to maintain strength and overall well-being. Working with a registered dietitian can help develop a personalized nutrition plan that meets individual needs, manages treatment-related side effects, and supports optimal health.
Pain Management: Pain is a common symptom in CRPC. An effective pain management plan may involve the use of medications, physical therapy, complementary therapies, and interventional procedures to alleviate pain and improve daily functioning.
Use of Interference with androgenic stimulation in Conventional adenocarcinomas
In CRPC, the cancer cells adapt and find alternative ways to grow and survive despite low testosterone levels achieved through ADT. This can occur through various mechanisms, including the overexpression of androgen receptor (AR) or the activation of alternative signaling pathways.
abiraterone:
abiraterone is an important treatment option in conventional adenocarcinomas, particularly in castration-resistant prostate cancer (CRPC). Here is more information specifically about the use of abiraterone in conventional adenocarcinomas:
abiraterone is an orally administered small molecule that inhibits the products of the cytochrome P450 family 17 (CYP17) gene, specifically 17,20-lyase and 17-alpha-hydroxylase. By blocking these enzymes, abiraterone effectively reduces the synthesis of androgens (male hormones) not only in tumor cells but also in the testes and adrenal glands.
In conventional adenocarcinomas, such as prostate cancer, androgens play a critical role in tumor growth and progression. By inhibiting androgen synthesis, abiraterone effectively disrupts the androgenic stimulation of tumor cells, leading to a reduction in tumor growth and progression.
abiraterone is primarily used in the treatment of castration-resistant prostate cancer (CRPC), which refers to prostate cancer that has progressed despite hormonal therapy (androgen deprivation therapy). It is effective in both chemotherapy-naĂŻve patients and those who have been previously treated with docetaxel chemotherapy.
enzalutamide, apalutamide, and darolutamide:
Enzalutamide, apalutamide, and darolutamide are all approved and used in the treatment of metastatic castration-resistant prostate cancer (mCRPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). Here is an overview of their use in these settings:
Metastatic CRPC (mCRPC):
Enzalutamide: It has been shown to improve overall survival in males with mCRPC, both in those who have previously been treated with docetaxel chemotherapy and in chemotherapy-naĂŻve patients. Enzalutamide is approved for the treatment of mCRPC and is associated with a low incidence of seizures. Pre-existing seizure disorders are not a contraindication to its use.
apalutamide: it is another androgen receptor inhibitor approved for the treatment of mCRPC. It has also demonstrated efficacy in improving overall survival in males with mCRPC, both in those who have received prior docetaxel chemotherapy and in chemotherapy-naĂŻve patients.
darolutamide: darolutamide is an androgen receptor inhibitor that has shown efficacy in the treatment of mCRPC. It has been shown to improve overall survival and delay disease progression in patients with mCRPC. Darolutamide is approved for the treatment of mCRPC.
Nonmetastatic CRPC (nmCRPC):
enzalutamide, apalutamide, and darolutamide have also demonstrated efficacy in the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC). These drugs have been studied in separate placebo-controlled randomized trials, enrolling patients with a short PSA doubling time (<10 months). All three agents are now approved by the US Food and Drug Administration (FDA) for the treatment of nmCRPC.
Use of Chemotherapy in Conventional adenocarcinomas
docetaxel:
It is a taxane chemotherapy drug that has shown significant efficacy in CRPC. It has been extensively studied and approved for the treatment of CRPC. It is typically used in patients who have progressed despite hormone therapy, including androgen deprivation therapy. The standard regimen for docetaxel in CRPC is 75 mg/m² given intravenously every three weeks in combination with daily prednisone (5 mg twice a day). This regimen has been shown to prolong overall survival compared to mitoxantrone plus prednisone, which was the previous standard of care.
cabazitaxel:
It is a synthetic taxane derivative that is active in patients with or without prior exposure to docetaxel. Cabazitaxel is often considered as an alternative to docetaxel, especially in older or frail patients and those at high risk for neutropenia. The recommended dose is 20 mg/m2.
Comparison of docetaxel and cabazitaxel:
Both docetaxel and cabazitaxel are chemotherapy drugs that belong to the taxane class and are commonly used in the treatment of various types of cancers, including adenocarcinomas.
In the context of prostate cancer, cabazitaxel has shown improved overall survival compared to docetaxel in patients with mCRPC. This led to its approval for use after docetaxel treatment failure in this specific setting.
Comparison with Other Treatments:
cabazitaxel vs Androgen Receptor Inhibitors: abiraterone acetate is an androgen biosynthesis inhibitor that is commonly used in the treatment of mCRPC. It works by inhibiting the production of androgens, which fuel the growth of prostate cancer cells. Abiraterone acetate is often used before or after chemotherapy, including docetaxel or cabazitaxel. The choice between cabazitaxel and abiraterone acetate depends on several factors, such as prior treatment history, disease progression, and patient characteristics.
mitoxantrone:
It is a chemotherapy agent that was initially approved for use in men with CRPC based on its ability to improve symptoms such as pain and quality of life, rather than prolonging overall survival.
mitoxantrone has been used in the treatment of several types of adenocarcinomas, its effectiveness and specific indications may vary depending on the organ affected.
radium-223 (Ra-223):
Ra-223 Radium-223 is a radioactive isotope used to treat certain types of cancer, particularly metastatic CRPC that have spread to the bones. It is an alpha particle-emitting radiopharmaceutical that targets areas of increased bone turnover.
Conventional adenocarcinomas, which include various types of cancers arising from glandular tissues, are typically not treated with radium-223. Radium-223 specifically targets bone metastases, and its mechanism of action is based on its ability to emit alpha particles that deliver localized radiation to cancer cells in the bones. Therefore, it is not effective in treating adenocarcinomas that have not spread to the bones.
sipuleucel-T
sipuleucel-T is an autologous cellular immunotherapy. It involves collecting a patient’s own immune cells called dendritic cells and exposing them to a fusion protein called PAP-GM-CSF, which consists of prostatic acid phosphatase (PAP) antigen and granulocyte-macrophage colony-stimulating factor (GM-CSF).
sipuleucel-T involves a series of three intravenous infusions given at two-week intervals. Each infusion contains the patient’s activated dendritic cells. The entire treatment process takes around four weeks
Use of Aggressive Variant Prostate Cancers in Conventional Adenocarcinomas
Aggressive variant prostate cancers refer to a subset of prostate cancers that display aggressive behavior and are associated with poor outcomes. These variants include neuroendocrine prostate cancer (NEPC), small cell carcinoma of the prostate (SCCP), and other rare histological subtypes. These aggressive variants have distinct biological characteristics compared to conventional adenocarcinomas of the prostate.
The management of CRPC with aggressive variant features typically involves a combination of systemic therapies, radiation therapy, and supportive care measures. The treatment of choice depends on various factors, including the extent of disease, the patient’s overall health, and individual treatment goals.
Systemic therapies are used in the treatment of CRPC with aggressive variants include chemotherapy agents, targeted therapies, and immunotherapy. Chemotherapy agents such as docetaxel and cabazitaxel may be utilized to target rapidly dividing cancer cells. Targeted therapies that inhibit specific pathways or molecules implicated in aggressive variant prostate cancers, such as PARP inhibitors or immune checkpoint inhibitors, may also be considered. Additionally, immunotherapy approaches such as immune checkpoint inhibitors may be explored to enhance the immune system’s response against cancer cells.
Medication
Indicated for Non-metastatic Castration-Resistant Prostate Cancer
600 mg orally 2 times a day
Continue until the disease is reduced to acceptable toxicity
Administer one implant once every 3 months
Future Trends
Castration-resistant prostate cancer (CRPC) is a stage of prostate cancer that progresses despite androgen deprivation therapy (ADT), which is the primary treatment for advanced prostate cancer. It is also known as hormone-refractory or androgen-independent prostate cancer. CRPC is characterized by the continued growth and spread of prostate cancer cells even without testosterone, the primary fuel for prostate cancer growth.
The development of CRPC is a complex process involving various molecular and cellular changes in the tumor cells. It is thought to arise from the selection and survival of cancer cells that have acquired mechanisms to bypass the androgen signaling pathway. These mechanisms include increased androgen receptor expression, activation of alternative signaling pathways, genetic alterations, and development of castration-resistant clones.
CRPC is associated with poor prognosis and represents a significant challenge in the management of advanced prostate cancer. It often leads to metastatic disease, spreading to other organs such as the bones, lymph nodes, or distant sites.
Incidence: The incidence of CRPC varies depending on the stage of prostate cancer and the population studied. It typically occurs in men who have received androgen deprivation therapy (ADT) for advanced prostate cancer.
Prevalence: CRPC accounts for a significant proportion of advanced prostate cancer cases. As prostate cancer is one of the most common cancers in men, the prevalence of CRPC is substantial.
Age: The risk of developing CRPC increases with age, and it is more commonly diagnosed in older men. However, it can occur in men of any age who have received ADT.
Racial and Ethnic Disparities: Studies have shown variations in the incidence and outcomes of CRPC among different racial and ethnic groups. African American men have been found to have a higher incidence and poorer prognosis compared to other populations.
Risk Factors: The development of CRPC includes advanced age, high initial prostate-specific antigen (PSA) levels, high Gleason score, and extent of disease at the time of diagnosis.
Androgen Receptor Signalling: The development and progression of prostate cancer are driven by androgen receptor signalling, which is stimulated by androgens such as testosterone. In CRPC, the cancer cells find alternative mechanisms to activate androgen receptor signalling despite low levels of circulating androgens.
Androgen Deprivation Therapy (ADT): ADT is a standard treatment for advanced prostate cancer that aims to lower androgen levels. Initially, ADT is effective in suppressing tumor growth, but over time, prostate cancer cells can adapt and become resistant to ADT, leading to the development of CRPC.
Androgen Receptor Alterations: CRPC is characterized by alterations in the androgen receptor (AR) pathway. These alterations can include amplification of the AR gene, mutations in the AR gene, or increased expression of co-activators that enhance AR signalling. These changes allow the cancer cells to bypass the need for circulating androgens and remain active even in low androgen environments.
Intratumoral Androgen Production: Another mechanism contributing to CRPC is the intratumoral production of androgens. Prostate cancer cells can synthesize androgens locally, allowing them to sustain androgen receptor signalling despite systemic androgen deprivation.
Activation of Alternative Signalling Pathways: In CRPC, cancer cells can activate alternative signalling pathways, such as the PI3K/AKT/mTOR pathway or the WNT/β-catenin pathway, which promote cell survival and growth independently of androgen receptor signalling.
Continued Androgen Production: In some cases of CRPC, the tumor cells develop the ability to produce androgens locally within the tumor microenvironment. This can occur through increased expression of enzymes involved in androgen synthesis, allowing the cancer cells to maintain androgen signalling despite systemic androgen deprivation.
Androgen Receptor Coactivators: Overexpression of coactivators that enhance AR signalling can contribute to the development of CRPC. These coactivators can facilitate AR activation even in the presence of low androgen levels.
Genetic Alterations: Genetic mutations and alterations in CRPC can affect various genes involved in cell cycle regulation, DNA repair mechanisms, and tumor suppressor pathways. These alterations contribute to the development of resistance to therapies and promote tumor growth.
Tumor Microenvironment: The tumor microenvironment plays a crucial role in the progression of CRPC. Interactions between cancer cells and surrounding stromal cells, immune cells, and cytokines contribute to the development of resistance mechanisms and promote tumor growth and metastasis.
PSA Doubling Time: PSA doubling time, which measures how quickly the prostate-specific antigen (PSA) levels double, is a strong prognostic factor in CRPC. A shorter PSA doubling time indicates more aggressive disease and poorer prognosis.
Gleason Score: The Gleason score, which is based on the histological assessment of prostate cancer cells, is a well-established prognostic factor for both localized and advanced prostate cancer. Higher Gleason scores (8-10) are associated with a higher risk of disease progression and poorer outcomes.
Disease Stage: The stage of CRPC at diagnosis is an important prognostic factor. Metastatic disease at the time of CRPC diagnosis indicates a higher disease burden and poorer prognosis compared to localized disease.
Performance Status: The performance status of a patient, often assessed using the Eastern Cooperative Oncology Group (ECOG) performance status scale, is a prognostic factor in CRPC. A better performance status indicates a higher level of physical functioning and is associated with improved outcomes.
Presence of Metastases: The presence and extent of metastases in CRPC, especially to vital organs such as the liver or lungs, are significant prognostic factors. Patients with extensive metastatic disease have a poorer prognosis compared to those with localized or limited metastases.
Serum LDH and ALP Levels: Elevated levels of serum lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) are associated with a higher tumor burden and poorer prognosis in CRPC. These biomarkers reflect disease activity and can help predict treatment response and survival.
Age Group:
Castration-resistant prostate cancer (CRPC) typically occurs in older men. The median age at diagnosis of CRPC is around 70 years, although it can be diagnosed in men of various age groups.
Digital Rectal Examination (DRE):
Genitourinary Examination:
Abdominal Examination:
Neurological Examination:
Bone Examination:
Patients with CRPC may have associated comorbidities such as cardiovascular disease, diabetes, hypertension, or other chronic conditions.
These comorbidities can impact treatment decisions and overall management.
The acuity of presentation in CRPC can vary depending on the disease course. Some patients may have a gradual progression of symptoms and biochemical markers, while others may experience a more rapid deterioration in their condition. Acute complications, such as spinal cord compression or skeletal-related events, can also occur in advanced cases.
Activity Level:
The activity level of patients with CRPC can vary depending on their overall health and disease progression. Some patients may experience fatigue or reduced energy levels due to the advanced stage of the disease, while others may maintain a normal activity level.
Benign Prostatic Hyperplasia (BPH):
Prostatitis:
Metastatic Cancer:
Prostate Intraepithelial Neoplasia (PIN):
Prostate Lymphoma:
Castration-Resistant Prostate Cancer (CRPC) involves a variety of therapeutic options aimed at slowing disease progression, relieving symptoms, and improving overall survival. The specific treatment approach depends on various factors such as disease extent, symptoms, prior treatments, patient preferences, and overall health.
Androgen Receptor (AR)-Targeted Therapies:
enzalutamide: An oral AR antagonist that inhibits AR signaling and can improve overall survival and delay disease progression.
abiraterone acetate: An oral medication that blocks the synthesis of androgens, including testosterone, and can improve survival when combined with prednisone.
apalutamide: Another oral AR antagonist that has shown efficacy in delaying disease progression and improving survival.
Chemotherapy:
docetaxel: A chemotherapy drug that can improve survival and quality of life when combined with prednisone. It is typically used in patients who have progressed after initial hormone therapy.
cabazitaxel: Another chemotherapy agent approved for use in CRPC after docetaxel treatment.
Immunotherapy:
Sipuleucel-T: A cellular immunotherapy that stimulates the patient’s immune system to target prostate cancer cells. It is typically used in asymptomatic or minimally symptomatic patients with metastatic CRPC.
Targeted Therapies:
Radium-223: A targeted alpha therapy that delivers radiation to bone metastases, providing palliative benefit and improving survival in patients with bone-dominant disease.
PARP inhibitors: Olaparib and rucaparib are approved for patients with certain genetic mutations, such as BRCA1/2, and can be effective in slowing disease progression.
Radiopharmaceuticals:
PSMA-targeted radioligand therapy: Radiopharmaceuticals such as lutetium-177 PSMA-617 or actinium-225 PSMA-617 can target prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation to tumors.
Other Therapies:
Palliative care: Supportive care to manage symptoms, improve quality of life, and address psychosocial needs.
Clinical trials: Participation in clinical trials investigating new treatments or combinations.
Nutrition
Oncology, Other
Oncology, Radiation
Plant-Based Foods: Include a variety of plant-based foods in diet, such as fruits, vegetables, whole grains, nuts, and seeds. These are rich in antioxidants, vitamins, minerals, and fiber, which can support overall health.
Healthy Fats: Incorporate healthy fats into your diet, such as olive oil, avocados, nuts, and seeds. These fats provide essential nutrients and may have anti-inflammatory properties.
Limit Saturated and Trans Fats: Reduce the intake of saturated fats found in red meat, full-fat dairy products, and fried foods. Minimize or avoid trans fats found in processed and packaged foods, as they can increase inflammation and negatively impact overall health.
Omega-3 Fatty Acids: Include omega-3 fatty acids in your diet, which can be found in fatty fish (such as salmon, sardines, and trout), walnuts, chia seeds, and flaxseeds. Omega-3 fatty acids have been associated with potential health benefits, including anti-inflammatory effects.
Oncology, Medical
Oncology, Other
Oncology, Radiation
Physical Medicine and Rehabilitation
Aerobic Exercise: Engage in regular aerobic exercises such as walking, cycling, swimming, or low-impact aerobics. Aim for at least 150 minutes or 75 minutes of aerobic activity, or a combination of both.
Strength Training: Incorporate strength training exercises to maintain or improve muscle strength and endurance. Resistance exercises using weights, resistance bands, or bodyweight can help preserve muscle mass and enhance overall physical function.
Flexibility and Stretching: Include flexibility exercises to improve joint mobility and flexibility. Stretching exercises, yoga, or tai chi can help maintain or improve flexibility and balance.
Balance and Stability Training:
consider incorporating balance and stability exercises to reduce the risk of falls and improve overall stability. These exercises can include standing on one leg, heel-to-toe walk, or exercises that challenge balance.
Oncology, Medical
Oncology, Other
Oncology, Radiation
Psychiatry/Mental Health
Relaxation Techniques: deep breathing exercises, progressive muscle relaxation, guided imagery, or meditation. These techniques can help reduce stress, promote relaxation, and improve overall well-being.
Mindfulness-Based Stress Reduction (MBSR): MBSR programs involve training in mindfulness meditation and can help individuals develop skills to manage stress and enhance coping mechanisms. Consider participating in MBSR programs offered by qualified instructors or using mobile apps and online resources for guided mindfulness practices.
Support Systems: Maintain a strong support network of family, friends, or support groups. Sharing your experiences, concerns, and emotions with others who are going through similar challenges can provide emotional support and help alleviate stress.
Counselling or Therapy: Consider seeking professional counselling or therapy to help manage stress and address any emotional concerns associated with CRPC. Individual counselling, support groups, or couples counselling can provide a safe space to discuss emotions, fears, and challenges related to the condition.
Oncology, Medical
Oncology, Other
Oncology, Radiation
Pain Management
Symptom Management: Addressing and managing symptoms associated with CRPC, such as pain, fatigue, nausea, and urinary or bowel problems, is essential. This may involve the use of medications, lifestyle modifications, physical therapy, and other interventions to alleviate symptoms and improve comfort.
Palliative Care: It is an important component of supportive care for CRPC. It focuses on relieving symptoms, managing pain, and improving quality of life. Palliative care teams work closely with patients and their families to address physical, emotional, and spiritual needs throughout the course of the disease.
Psychological and Emotional Support: The emotional impact of CRPC can be significant. Providing psychological support, counselling, and access to support groups can help individuals cope with the emotional challenges associated with the condition. Psychosocial support can also extend to family members and caregivers.
Nutritional Support: Proper nutrition is essential for individuals with CRPC to maintain strength and overall well-being. Working with a registered dietitian can help develop a personalized nutrition plan that meets individual needs, manages treatment-related side effects, and supports optimal health.
Pain Management: Pain is a common symptom in CRPC. An effective pain management plan may involve the use of medications, physical therapy, complementary therapies, and interventional procedures to alleviate pain and improve daily functioning.
Oncology, Medical
Oncology, Other
Oncology, Radiation
Urology
In CRPC, the cancer cells adapt and find alternative ways to grow and survive despite low testosterone levels achieved through ADT. This can occur through various mechanisms, including the overexpression of androgen receptor (AR) or the activation of alternative signaling pathways.
abiraterone:
abiraterone is an important treatment option in conventional adenocarcinomas, particularly in castration-resistant prostate cancer (CRPC). Here is more information specifically about the use of abiraterone in conventional adenocarcinomas:
abiraterone is an orally administered small molecule that inhibits the products of the cytochrome P450 family 17 (CYP17) gene, specifically 17,20-lyase and 17-alpha-hydroxylase. By blocking these enzymes, abiraterone effectively reduces the synthesis of androgens (male hormones) not only in tumor cells but also in the testes and adrenal glands.
In conventional adenocarcinomas, such as prostate cancer, androgens play a critical role in tumor growth and progression. By inhibiting androgen synthesis, abiraterone effectively disrupts the androgenic stimulation of tumor cells, leading to a reduction in tumor growth and progression.
abiraterone is primarily used in the treatment of castration-resistant prostate cancer (CRPC), which refers to prostate cancer that has progressed despite hormonal therapy (androgen deprivation therapy). It is effective in both chemotherapy-naĂŻve patients and those who have been previously treated with docetaxel chemotherapy.
enzalutamide, apalutamide, and darolutamide:
Enzalutamide, apalutamide, and darolutamide are all approved and used in the treatment of metastatic castration-resistant prostate cancer (mCRPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). Here is an overview of their use in these settings:
Metastatic CRPC (mCRPC):
Enzalutamide: It has been shown to improve overall survival in males with mCRPC, both in those who have previously been treated with docetaxel chemotherapy and in chemotherapy-naĂŻve patients. Enzalutamide is approved for the treatment of mCRPC and is associated with a low incidence of seizures. Pre-existing seizure disorders are not a contraindication to its use.
apalutamide: it is another androgen receptor inhibitor approved for the treatment of mCRPC. It has also demonstrated efficacy in improving overall survival in males with mCRPC, both in those who have received prior docetaxel chemotherapy and in chemotherapy-naĂŻve patients.
darolutamide: darolutamide is an androgen receptor inhibitor that has shown efficacy in the treatment of mCRPC. It has been shown to improve overall survival and delay disease progression in patients with mCRPC. Darolutamide is approved for the treatment of mCRPC.
Nonmetastatic CRPC (nmCRPC):
enzalutamide, apalutamide, and darolutamide have also demonstrated efficacy in the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC). These drugs have been studied in separate placebo-controlled randomized trials, enrolling patients with a short PSA doubling time (<10 months). All three agents are now approved by the US Food and Drug Administration (FDA) for the treatment of nmCRPC.
Oncology, Medical
Oncology, Other
Oncology, Radiation
Urology
docetaxel:
It is a taxane chemotherapy drug that has shown significant efficacy in CRPC. It has been extensively studied and approved for the treatment of CRPC. It is typically used in patients who have progressed despite hormone therapy, including androgen deprivation therapy. The standard regimen for docetaxel in CRPC is 75 mg/m² given intravenously every three weeks in combination with daily prednisone (5 mg twice a day). This regimen has been shown to prolong overall survival compared to mitoxantrone plus prednisone, which was the previous standard of care.
cabazitaxel:
It is a synthetic taxane derivative that is active in patients with or without prior exposure to docetaxel. Cabazitaxel is often considered as an alternative to docetaxel, especially in older or frail patients and those at high risk for neutropenia. The recommended dose is 20 mg/m2.
Comparison of docetaxel and cabazitaxel:
Both docetaxel and cabazitaxel are chemotherapy drugs that belong to the taxane class and are commonly used in the treatment of various types of cancers, including adenocarcinomas.
In the context of prostate cancer, cabazitaxel has shown improved overall survival compared to docetaxel in patients with mCRPC. This led to its approval for use after docetaxel treatment failure in this specific setting.
Comparison with Other Treatments:
cabazitaxel vs Androgen Receptor Inhibitors: abiraterone acetate is an androgen biosynthesis inhibitor that is commonly used in the treatment of mCRPC. It works by inhibiting the production of androgens, which fuel the growth of prostate cancer cells. Abiraterone acetate is often used before or after chemotherapy, including docetaxel or cabazitaxel. The choice between cabazitaxel and abiraterone acetate depends on several factors, such as prior treatment history, disease progression, and patient characteristics.
mitoxantrone:
It is a chemotherapy agent that was initially approved for use in men with CRPC based on its ability to improve symptoms such as pain and quality of life, rather than prolonging overall survival.
mitoxantrone has been used in the treatment of several types of adenocarcinomas, its effectiveness and specific indications may vary depending on the organ affected.
radium-223 (Ra-223):
Ra-223 Radium-223 is a radioactive isotope used to treat certain types of cancer, particularly metastatic CRPC that have spread to the bones. It is an alpha particle-emitting radiopharmaceutical that targets areas of increased bone turnover.
Conventional adenocarcinomas, which include various types of cancers arising from glandular tissues, are typically not treated with radium-223. Radium-223 specifically targets bone metastases, and its mechanism of action is based on its ability to emit alpha particles that deliver localized radiation to cancer cells in the bones. Therefore, it is not effective in treating adenocarcinomas that have not spread to the bones.
sipuleucel-T
sipuleucel-T is an autologous cellular immunotherapy. It involves collecting a patient’s own immune cells called dendritic cells and exposing them to a fusion protein called PAP-GM-CSF, which consists of prostatic acid phosphatase (PAP) antigen and granulocyte-macrophage colony-stimulating factor (GM-CSF).
sipuleucel-T involves a series of three intravenous infusions given at two-week intervals. Each infusion contains the patient’s activated dendritic cells. The entire treatment process takes around four weeks
Oncology, Medical
Oncology, Other
Oncology, Radiation
Aggressive variant prostate cancers refer to a subset of prostate cancers that display aggressive behavior and are associated with poor outcomes. These variants include neuroendocrine prostate cancer (NEPC), small cell carcinoma of the prostate (SCCP), and other rare histological subtypes. These aggressive variants have distinct biological characteristics compared to conventional adenocarcinomas of the prostate.
The management of CRPC with aggressive variant features typically involves a combination of systemic therapies, radiation therapy, and supportive care measures. The treatment of choice depends on various factors, including the extent of disease, the patient’s overall health, and individual treatment goals.
Systemic therapies are used in the treatment of CRPC with aggressive variants include chemotherapy agents, targeted therapies, and immunotherapy. Chemotherapy agents such as docetaxel and cabazitaxel may be utilized to target rapidly dividing cancer cells. Targeted therapies that inhibit specific pathways or molecules implicated in aggressive variant prostate cancers, such as PARP inhibitors or immune checkpoint inhibitors, may also be considered. Additionally, immunotherapy approaches such as immune checkpoint inhibitors may be explored to enhance the immune system’s response against cancer cells.
Castration-resistant prostate cancer (CRPC) is a stage of prostate cancer that progresses despite androgen deprivation therapy (ADT), which is the primary treatment for advanced prostate cancer. It is also known as hormone-refractory or androgen-independent prostate cancer. CRPC is characterized by the continued growth and spread of prostate cancer cells even without testosterone, the primary fuel for prostate cancer growth.
The development of CRPC is a complex process involving various molecular and cellular changes in the tumor cells. It is thought to arise from the selection and survival of cancer cells that have acquired mechanisms to bypass the androgen signaling pathway. These mechanisms include increased androgen receptor expression, activation of alternative signaling pathways, genetic alterations, and development of castration-resistant clones.
CRPC is associated with poor prognosis and represents a significant challenge in the management of advanced prostate cancer. It often leads to metastatic disease, spreading to other organs such as the bones, lymph nodes, or distant sites.
Incidence: The incidence of CRPC varies depending on the stage of prostate cancer and the population studied. It typically occurs in men who have received androgen deprivation therapy (ADT) for advanced prostate cancer.
Prevalence: CRPC accounts for a significant proportion of advanced prostate cancer cases. As prostate cancer is one of the most common cancers in men, the prevalence of CRPC is substantial.
Age: The risk of developing CRPC increases with age, and it is more commonly diagnosed in older men. However, it can occur in men of any age who have received ADT.
Racial and Ethnic Disparities: Studies have shown variations in the incidence and outcomes of CRPC among different racial and ethnic groups. African American men have been found to have a higher incidence and poorer prognosis compared to other populations.
Risk Factors: The development of CRPC includes advanced age, high initial prostate-specific antigen (PSA) levels, high Gleason score, and extent of disease at the time of diagnosis.
Androgen Receptor Signalling: The development and progression of prostate cancer are driven by androgen receptor signalling, which is stimulated by androgens such as testosterone. In CRPC, the cancer cells find alternative mechanisms to activate androgen receptor signalling despite low levels of circulating androgens.
Androgen Deprivation Therapy (ADT): ADT is a standard treatment for advanced prostate cancer that aims to lower androgen levels. Initially, ADT is effective in suppressing tumor growth, but over time, prostate cancer cells can adapt and become resistant to ADT, leading to the development of CRPC.
Androgen Receptor Alterations: CRPC is characterized by alterations in the androgen receptor (AR) pathway. These alterations can include amplification of the AR gene, mutations in the AR gene, or increased expression of co-activators that enhance AR signalling. These changes allow the cancer cells to bypass the need for circulating androgens and remain active even in low androgen environments.
Intratumoral Androgen Production: Another mechanism contributing to CRPC is the intratumoral production of androgens. Prostate cancer cells can synthesize androgens locally, allowing them to sustain androgen receptor signalling despite systemic androgen deprivation.
Activation of Alternative Signalling Pathways: In CRPC, cancer cells can activate alternative signalling pathways, such as the PI3K/AKT/mTOR pathway or the WNT/β-catenin pathway, which promote cell survival and growth independently of androgen receptor signalling.
Continued Androgen Production: In some cases of CRPC, the tumor cells develop the ability to produce androgens locally within the tumor microenvironment. This can occur through increased expression of enzymes involved in androgen synthesis, allowing the cancer cells to maintain androgen signalling despite systemic androgen deprivation.
Androgen Receptor Coactivators: Overexpression of coactivators that enhance AR signalling can contribute to the development of CRPC. These coactivators can facilitate AR activation even in the presence of low androgen levels.
Genetic Alterations: Genetic mutations and alterations in CRPC can affect various genes involved in cell cycle regulation, DNA repair mechanisms, and tumor suppressor pathways. These alterations contribute to the development of resistance to therapies and promote tumor growth.
Tumor Microenvironment: The tumor microenvironment plays a crucial role in the progression of CRPC. Interactions between cancer cells and surrounding stromal cells, immune cells, and cytokines contribute to the development of resistance mechanisms and promote tumor growth and metastasis.
PSA Doubling Time: PSA doubling time, which measures how quickly the prostate-specific antigen (PSA) levels double, is a strong prognostic factor in CRPC. A shorter PSA doubling time indicates more aggressive disease and poorer prognosis.
Gleason Score: The Gleason score, which is based on the histological assessment of prostate cancer cells, is a well-established prognostic factor for both localized and advanced prostate cancer. Higher Gleason scores (8-10) are associated with a higher risk of disease progression and poorer outcomes.
Disease Stage: The stage of CRPC at diagnosis is an important prognostic factor. Metastatic disease at the time of CRPC diagnosis indicates a higher disease burden and poorer prognosis compared to localized disease.
Performance Status: The performance status of a patient, often assessed using the Eastern Cooperative Oncology Group (ECOG) performance status scale, is a prognostic factor in CRPC. A better performance status indicates a higher level of physical functioning and is associated with improved outcomes.
Presence of Metastases: The presence and extent of metastases in CRPC, especially to vital organs such as the liver or lungs, are significant prognostic factors. Patients with extensive metastatic disease have a poorer prognosis compared to those with localized or limited metastases.
Serum LDH and ALP Levels: Elevated levels of serum lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) are associated with a higher tumor burden and poorer prognosis in CRPC. These biomarkers reflect disease activity and can help predict treatment response and survival.
Age Group:
Castration-resistant prostate cancer (CRPC) typically occurs in older men. The median age at diagnosis of CRPC is around 70 years, although it can be diagnosed in men of various age groups.
Digital Rectal Examination (DRE):
Genitourinary Examination:
Abdominal Examination:
Neurological Examination:
Bone Examination:
Patients with CRPC may have associated comorbidities such as cardiovascular disease, diabetes, hypertension, or other chronic conditions.
These comorbidities can impact treatment decisions and overall management.
The acuity of presentation in CRPC can vary depending on the disease course. Some patients may have a gradual progression of symptoms and biochemical markers, while others may experience a more rapid deterioration in their condition. Acute complications, such as spinal cord compression or skeletal-related events, can also occur in advanced cases.
Activity Level:
The activity level of patients with CRPC can vary depending on their overall health and disease progression. Some patients may experience fatigue or reduced energy levels due to the advanced stage of the disease, while others may maintain a normal activity level.
Benign Prostatic Hyperplasia (BPH):
Prostatitis:
Metastatic Cancer:
Prostate Intraepithelial Neoplasia (PIN):
Prostate Lymphoma:
Castration-Resistant Prostate Cancer (CRPC) involves a variety of therapeutic options aimed at slowing disease progression, relieving symptoms, and improving overall survival. The specific treatment approach depends on various factors such as disease extent, symptoms, prior treatments, patient preferences, and overall health.
Androgen Receptor (AR)-Targeted Therapies:
enzalutamide: An oral AR antagonist that inhibits AR signaling and can improve overall survival and delay disease progression.
abiraterone acetate: An oral medication that blocks the synthesis of androgens, including testosterone, and can improve survival when combined with prednisone.
apalutamide: Another oral AR antagonist that has shown efficacy in delaying disease progression and improving survival.
Chemotherapy:
docetaxel: A chemotherapy drug that can improve survival and quality of life when combined with prednisone. It is typically used in patients who have progressed after initial hormone therapy.
cabazitaxel: Another chemotherapy agent approved for use in CRPC after docetaxel treatment.
Immunotherapy:
Sipuleucel-T: A cellular immunotherapy that stimulates the patient’s immune system to target prostate cancer cells. It is typically used in asymptomatic or minimally symptomatic patients with metastatic CRPC.
Targeted Therapies:
Radium-223: A targeted alpha therapy that delivers radiation to bone metastases, providing palliative benefit and improving survival in patients with bone-dominant disease.
PARP inhibitors: Olaparib and rucaparib are approved for patients with certain genetic mutations, such as BRCA1/2, and can be effective in slowing disease progression.
Radiopharmaceuticals:
PSMA-targeted radioligand therapy: Radiopharmaceuticals such as lutetium-177 PSMA-617 or actinium-225 PSMA-617 can target prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation to tumors.
Other Therapies:
Palliative care: Supportive care to manage symptoms, improve quality of life, and address psychosocial needs.
Clinical trials: Participation in clinical trials investigating new treatments or combinations.
Nutrition
Oncology, Other
Oncology, Radiation
Plant-Based Foods: Include a variety of plant-based foods in diet, such as fruits, vegetables, whole grains, nuts, and seeds. These are rich in antioxidants, vitamins, minerals, and fiber, which can support overall health.
Healthy Fats: Incorporate healthy fats into your diet, such as olive oil, avocados, nuts, and seeds. These fats provide essential nutrients and may have anti-inflammatory properties.
Limit Saturated and Trans Fats: Reduce the intake of saturated fats found in red meat, full-fat dairy products, and fried foods. Minimize or avoid trans fats found in processed and packaged foods, as they can increase inflammation and negatively impact overall health.
Omega-3 Fatty Acids: Include omega-3 fatty acids in your diet, which can be found in fatty fish (such as salmon, sardines, and trout), walnuts, chia seeds, and flaxseeds. Omega-3 fatty acids have been associated with potential health benefits, including anti-inflammatory effects.
Oncology, Medical
Oncology, Other
Oncology, Radiation
Physical Medicine and Rehabilitation
Aerobic Exercise: Engage in regular aerobic exercises such as walking, cycling, swimming, or low-impact aerobics. Aim for at least 150 minutes or 75 minutes of aerobic activity, or a combination of both.
Strength Training: Incorporate strength training exercises to maintain or improve muscle strength and endurance. Resistance exercises using weights, resistance bands, or bodyweight can help preserve muscle mass and enhance overall physical function.
Flexibility and Stretching: Include flexibility exercises to improve joint mobility and flexibility. Stretching exercises, yoga, or tai chi can help maintain or improve flexibility and balance.
Balance and Stability Training:
consider incorporating balance and stability exercises to reduce the risk of falls and improve overall stability. These exercises can include standing on one leg, heel-to-toe walk, or exercises that challenge balance.
Oncology, Medical
Oncology, Other
Oncology, Radiation
Psychiatry/Mental Health
Relaxation Techniques: deep breathing exercises, progressive muscle relaxation, guided imagery, or meditation. These techniques can help reduce stress, promote relaxation, and improve overall well-being.
Mindfulness-Based Stress Reduction (MBSR): MBSR programs involve training in mindfulness meditation and can help individuals develop skills to manage stress and enhance coping mechanisms. Consider participating in MBSR programs offered by qualified instructors or using mobile apps and online resources for guided mindfulness practices.
Support Systems: Maintain a strong support network of family, friends, or support groups. Sharing your experiences, concerns, and emotions with others who are going through similar challenges can provide emotional support and help alleviate stress.
Counselling or Therapy: Consider seeking professional counselling or therapy to help manage stress and address any emotional concerns associated with CRPC. Individual counselling, support groups, or couples counselling can provide a safe space to discuss emotions, fears, and challenges related to the condition.
Oncology, Medical
Oncology, Other
Oncology, Radiation
Pain Management
Symptom Management: Addressing and managing symptoms associated with CRPC, such as pain, fatigue, nausea, and urinary or bowel problems, is essential. This may involve the use of medications, lifestyle modifications, physical therapy, and other interventions to alleviate symptoms and improve comfort.
Palliative Care: It is an important component of supportive care for CRPC. It focuses on relieving symptoms, managing pain, and improving quality of life. Palliative care teams work closely with patients and their families to address physical, emotional, and spiritual needs throughout the course of the disease.
Psychological and Emotional Support: The emotional impact of CRPC can be significant. Providing psychological support, counselling, and access to support groups can help individuals cope with the emotional challenges associated with the condition. Psychosocial support can also extend to family members and caregivers.
Nutritional Support: Proper nutrition is essential for individuals with CRPC to maintain strength and overall well-being. Working with a registered dietitian can help develop a personalized nutrition plan that meets individual needs, manages treatment-related side effects, and supports optimal health.
Pain Management: Pain is a common symptom in CRPC. An effective pain management plan may involve the use of medications, physical therapy, complementary therapies, and interventional procedures to alleviate pain and improve daily functioning.
Oncology, Medical
Oncology, Other
Oncology, Radiation
Urology
In CRPC, the cancer cells adapt and find alternative ways to grow and survive despite low testosterone levels achieved through ADT. This can occur through various mechanisms, including the overexpression of androgen receptor (AR) or the activation of alternative signaling pathways.
abiraterone:
abiraterone is an important treatment option in conventional adenocarcinomas, particularly in castration-resistant prostate cancer (CRPC). Here is more information specifically about the use of abiraterone in conventional adenocarcinomas:
abiraterone is an orally administered small molecule that inhibits the products of the cytochrome P450 family 17 (CYP17) gene, specifically 17,20-lyase and 17-alpha-hydroxylase. By blocking these enzymes, abiraterone effectively reduces the synthesis of androgens (male hormones) not only in tumor cells but also in the testes and adrenal glands.
In conventional adenocarcinomas, such as prostate cancer, androgens play a critical role in tumor growth and progression. By inhibiting androgen synthesis, abiraterone effectively disrupts the androgenic stimulation of tumor cells, leading to a reduction in tumor growth and progression.
abiraterone is primarily used in the treatment of castration-resistant prostate cancer (CRPC), which refers to prostate cancer that has progressed despite hormonal therapy (androgen deprivation therapy). It is effective in both chemotherapy-naĂŻve patients and those who have been previously treated with docetaxel chemotherapy.
enzalutamide, apalutamide, and darolutamide:
Enzalutamide, apalutamide, and darolutamide are all approved and used in the treatment of metastatic castration-resistant prostate cancer (mCRPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). Here is an overview of their use in these settings:
Metastatic CRPC (mCRPC):
Enzalutamide: It has been shown to improve overall survival in males with mCRPC, both in those who have previously been treated with docetaxel chemotherapy and in chemotherapy-naĂŻve patients. Enzalutamide is approved for the treatment of mCRPC and is associated with a low incidence of seizures. Pre-existing seizure disorders are not a contraindication to its use.
apalutamide: it is another androgen receptor inhibitor approved for the treatment of mCRPC. It has also demonstrated efficacy in improving overall survival in males with mCRPC, both in those who have received prior docetaxel chemotherapy and in chemotherapy-naĂŻve patients.
darolutamide: darolutamide is an androgen receptor inhibitor that has shown efficacy in the treatment of mCRPC. It has been shown to improve overall survival and delay disease progression in patients with mCRPC. Darolutamide is approved for the treatment of mCRPC.
Nonmetastatic CRPC (nmCRPC):
enzalutamide, apalutamide, and darolutamide have also demonstrated efficacy in the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC). These drugs have been studied in separate placebo-controlled randomized trials, enrolling patients with a short PSA doubling time (<10 months). All three agents are now approved by the US Food and Drug Administration (FDA) for the treatment of nmCRPC.
Oncology, Medical
Oncology, Other
Oncology, Radiation
Urology
docetaxel:
It is a taxane chemotherapy drug that has shown significant efficacy in CRPC. It has been extensively studied and approved for the treatment of CRPC. It is typically used in patients who have progressed despite hormone therapy, including androgen deprivation therapy. The standard regimen for docetaxel in CRPC is 75 mg/m² given intravenously every three weeks in combination with daily prednisone (5 mg twice a day). This regimen has been shown to prolong overall survival compared to mitoxantrone plus prednisone, which was the previous standard of care.
cabazitaxel:
It is a synthetic taxane derivative that is active in patients with or without prior exposure to docetaxel. Cabazitaxel is often considered as an alternative to docetaxel, especially in older or frail patients and those at high risk for neutropenia. The recommended dose is 20 mg/m2.
Comparison of docetaxel and cabazitaxel:
Both docetaxel and cabazitaxel are chemotherapy drugs that belong to the taxane class and are commonly used in the treatment of various types of cancers, including adenocarcinomas.
In the context of prostate cancer, cabazitaxel has shown improved overall survival compared to docetaxel in patients with mCRPC. This led to its approval for use after docetaxel treatment failure in this specific setting.
Comparison with Other Treatments:
cabazitaxel vs Androgen Receptor Inhibitors: abiraterone acetate is an androgen biosynthesis inhibitor that is commonly used in the treatment of mCRPC. It works by inhibiting the production of androgens, which fuel the growth of prostate cancer cells. Abiraterone acetate is often used before or after chemotherapy, including docetaxel or cabazitaxel. The choice between cabazitaxel and abiraterone acetate depends on several factors, such as prior treatment history, disease progression, and patient characteristics.
mitoxantrone:
It is a chemotherapy agent that was initially approved for use in men with CRPC based on its ability to improve symptoms such as pain and quality of life, rather than prolonging overall survival.
mitoxantrone has been used in the treatment of several types of adenocarcinomas, its effectiveness and specific indications may vary depending on the organ affected.
radium-223 (Ra-223):
Ra-223 Radium-223 is a radioactive isotope used to treat certain types of cancer, particularly metastatic CRPC that have spread to the bones. It is an alpha particle-emitting radiopharmaceutical that targets areas of increased bone turnover.
Conventional adenocarcinomas, which include various types of cancers arising from glandular tissues, are typically not treated with radium-223. Radium-223 specifically targets bone metastases, and its mechanism of action is based on its ability to emit alpha particles that deliver localized radiation to cancer cells in the bones. Therefore, it is not effective in treating adenocarcinomas that have not spread to the bones.
sipuleucel-T
sipuleucel-T is an autologous cellular immunotherapy. It involves collecting a patient’s own immune cells called dendritic cells and exposing them to a fusion protein called PAP-GM-CSF, which consists of prostatic acid phosphatase (PAP) antigen and granulocyte-macrophage colony-stimulating factor (GM-CSF).
sipuleucel-T involves a series of three intravenous infusions given at two-week intervals. Each infusion contains the patient’s activated dendritic cells. The entire treatment process takes around four weeks
Oncology, Medical
Oncology, Other
Oncology, Radiation
Aggressive variant prostate cancers refer to a subset of prostate cancers that display aggressive behavior and are associated with poor outcomes. These variants include neuroendocrine prostate cancer (NEPC), small cell carcinoma of the prostate (SCCP), and other rare histological subtypes. These aggressive variants have distinct biological characteristics compared to conventional adenocarcinomas of the prostate.
The management of CRPC with aggressive variant features typically involves a combination of systemic therapies, radiation therapy, and supportive care measures. The treatment of choice depends on various factors, including the extent of disease, the patient’s overall health, and individual treatment goals.
Systemic therapies are used in the treatment of CRPC with aggressive variants include chemotherapy agents, targeted therapies, and immunotherapy. Chemotherapy agents such as docetaxel and cabazitaxel may be utilized to target rapidly dividing cancer cells. Targeted therapies that inhibit specific pathways or molecules implicated in aggressive variant prostate cancers, such as PARP inhibitors or immune checkpoint inhibitors, may also be considered. Additionally, immunotherapy approaches such as immune checkpoint inhibitors may be explored to enhance the immune system’s response against cancer cells.
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