Treatment planning for
advanced prostate
cancer (aPC)

Therapy in aPC aims to extend life, prevent complications, and maintain quality of life and performance status¹

It’s critical to take performance status (PS) and predicted life expectancy into account when conducting clinical decision-making for aPC^1,2 

PS can help determine the balance of risk and benefit associated with treatment for aPC. Commonly used scales to determine PS include the Eastern Cooperative Oncology Group (ECOG) scale and the Karnofsky scale.³

ECOG scale ranges from 0-5, with 0 being fully functional and 5 being deceased
Karnofsky scale ranges from 10-100, with 10 being a moribund individual and 100 being an individual with no limitations

In addition to PS, keep in mind the likelihood that a treatment will improve aPC-related symptoms and if it will drive meaningful improvement in PS.²

Assessing both PS and life expectancy are crucial to establishing goals of care and keeping the patient and patient’s family preferences best aligned with available treatment options.¹

Assessing which treatments are most appropriate for your patients

It’s important to choose a treatment plan based on PS, tumor characteristics, life expectancy, and comorbidities. In addition, factors such as risk stratification of the cancer and if the cancer is castration resistant or castration sensitive also need to be considered.^1,2 Finally, patient preferences for treatment are taken into account to ensure optimal outcomes.

Consideration of current and past treatments, additional medications and side effects experienced are key to develop an optimal treatment plan for your patients now and in the future.

The potential for recurring side effects and/or repeat adverse reactions should be recognized and shared with your patients and their care partners.

Before deciding on a treatment approach, determine if the patient is an appropriate candidate for germline and somatic genetic testing. Results from these genetic tests should be considered, as they can help determine the most appropriate treatment path for your patient

Importance of using androgen deprivation therapy (ADT) throughout treatment

ADT is beneficial throughout the prostate cancer care continuum, as it can slow or stop growth in advanced prostate cancer by lowering testosterone (T) and provides a foundation for other treatments. Once a patient begins to progress, from localized to metastatic hormone-sensitive or -resistant prostate cancer, treatment options change, but ADT can be used regardless, as it is considered the foundation of care for locally advanced or advanced prostate cancer, as shown below.^4,5

ADT provides a strong foundation of care throughout every stage of aPC^4,6,7

Agonists and antagonists

With different ADT options available, it’s important to know which type is most appropriate for your specific patient. LHRH agonists and antagonists are types of ADT that reduce the production of luteinizing hormone (LH), resulting in castrate levels of T, but they work in different ways.

	Agonists^5,8-13	Antagonists^5,8-13
Mechanism of action	Work by overstimulating the LHRH (also known as GnRH) receptors in the anterior pituitary gland, which desensitizes them over time. Continual binding of the agonists to the LHRH receptors results in an initial increase in LH release and T production, followed by a steep drop in both. Patients will reach clinically castrate levels of T in 2 to 4 weeks.	Work by blocking the GnRH (gonadotropin-releasing hormone) receptors in the pituitary gland, causing a faster decrease in LH and T, with castrate levels being reached in 2 to 3 days.
Benefits of initiating	Long-acting formulations provide patients with reliable, controlled suppression over time, which may help avoid periods of T breakthrough above castrate levels.	May benefit patients with spinal metastases due to the absence of initial T increase and others who require a rapid T suppression.
Route of delivery	Injected subcutaneously or intramuscularly.	Subcutaneous injection or oral.
Administration schedule	Depending on the product, can be administered monthly, every 3 or 4 months, or even just twice per year.	Taken once a day orally or injected every month.
Dosing flexibility	More availability in dosing options.	Limited dosing options.
Drug interactions	No known drug interactions.	Many drug-drug interactions are known for the oral formulation.

Mechanism of action
Agonists^5,8-13
Work by overstimulating the LHRH (also known as GnRH) receptors in the anterior pituitary gland, which desensitizes them over time. Continual binding of the agonists to the LHRH receptors results in an initial increase in LH release and T production, followed by a steep drop in both. Patients will reach clinically castrate levels of T in 2 to 4 weeks.
Antagonists^5,8-13
Work by blocking the GnRH (gonadotropin-releasing hormone) receptors in the pituitary gland, causing a faster decrease in LH and T, with castrate levels being reached in 2 to 3 days.

Benefits of initiating
Agonists^5,8-13
Long-acting formulations provide patients with reliable, controlled suppression over time, which may help avoid periods of T breakthrough above castrate levels.
Antagonists^5,8-13
May benefit patients with spinal metastases due to the absence of initial T increase and others who require a rapid T suppression.

Route of delivery
Agonists^5,8-13
Injected subcutaneously or intramuscularly.
Antagonists^5-11
Subcutaneous injection or oral.

Administration schedule
Agonists^5,8-13
Depending on the product, can be administered monthly, every 3 or 4 months, or even just twice per year.
Antagonists^5-11
Taken once a day orally or injected every month.

Drug interactions
Agonists^5,8-13
No known drug interactions.
Antagonists^5,8-13
Many drug-drug interactions are known for the oral formulation.

Deciding between agonist and antagonist should be dependent upon patient needs for rapid T reduction, patient adherence capabilities, age, medication burden, transportation status, cognitive function, and attributes like patient muscle mass and motility

Determining prognosis and creating treatment plans for specific aPC stages

aPC stage	How to determine prognosis	Treatments available
Biochemical recurrence^2,14	Counsel patients of the risk of developing metastatic disease. Continue PSA measurements and clinical evaluations. Consider radiographic assessments based on overall PSA and PSA kinetics. If PSADT <12 months, perform periodic staging evaluations consisting of cross-sectional imaging such as CT or MRI and technetium bone scan and/or PSMA-PET.	If no metastatic disease is shown on imaging, observe or offer clinical trial enrollment. ADT and enzalutamide for patients with high-risk biochemical recurrence.
mCSPC²	Assess the extent of metastatic disease (low vs high volume)—high-volume is defined as ≥4 bone metastases with at least one metastasis outside of the spine/pelvis and/or the presence of visceral metastases. Assess if newly diagnosed mCSPC patient is experiencing symptoms from metastatic disease at time of presentation to guide discussions of prognosis and further disease management. Obtain baseline PSA and serial PSA at 3-to-6-month intervals after initiation of ADT and consider periodic conventional imaging. Offer genetic testing.	ADT with GnRH agonists or antagonists or surgical castration. ADT in combination with either ARPI (abiraterone acetate plus prednisone, apalutamide, enzalutamide) or chemotherapy (docetaxel). In patients with de novo mCSPC, ADT in combination with docetaxel and either abiraterone acetate plus prednisone or darolutamide. In mCSPC patients with low-volume metastatic disease, primary radiotherapy to the prostate in combination with ADT. Do not offer bicalutamide, flutamide, or nilutamide in combination with GnRH agonists, except to block T flares. Do not offer oral ARPI without ADT.
nmCRPC²	Obtain serial PSA measurements at 3-to-6-month intervals. Calculate a PSADT starting at the time of development of castration resistance. Assess patients for development of metastatic disease using conventional or PSMA-PET imaging at intervals of 6-to-12 months.	Apalutamide, darolutamide, and enzalutamide with continued ADT for those at high risk for developing metastatic disease (PSADT ≤10 months). Observe those with continued ADT who are at lower risk (PSADT >10 months) for developing metastatic disease. Do not offer systemic chemotherapy or immunotherapy outside of a clinical trial.
mCRPC^2,15,16	Obtain baseline labs (eg, PSA, testosterone, LDH, Hgb, alkaline phosphatase level) and review location of metastatic disease (lymph node, bone, visceral), disease-related symptoms, and PS to inform discussions of prognosis and treatment decision-making. In mCRPC patients without PSA progression or new symptoms, perform imaging at least annually. In mCRPC patients with disease progression (PSA or radiographic progression or new disease-related symptoms) having previously received docetaxel and androgen pathway inhibitor, who are considering ¹⁷⁷Lu-PSMA-617, order PSMA-PET imaging. Offer genetic testing.	In newly diagnosed mCRPC patients who have not received prior ARPIs, continue ADT with abiraterone acetate plus prednisone, docetaxel, or enzalutamide. If one ARPI fails, it is possible to use another, but it may also be more likely to fail Sipuleucel-T before chemotherapy in patients who are asymptomatic or minimally symptomatic. Radium-223 for patients with painful bone metastases and without known visceral disease or lymphadenopathy. ¹⁷⁷Lu-PSMA-617 in patients who have received docetaxel and ARPI and have cancer visible on PSMA-PET. Taxane chemotherapy given with prednisone (docetaxel and cabazitaxel). For patients who received prior docetaxel with or without prior abiraterone acetate plus prednisone or enzalutamide for CRPC, offer cabazitaxel PARP inhibitors for patients with deleterious or suspected deleterious germline or somatic HRR gene-mutated mCRPC following prior treatment with enzalutamide or abiraterone acetate and/or a taxane-based chemotherapy. Platinum-based chemotherapy such as carboplatin for those who cannot use or obtain a PARPi For patients with MMR deficient or MSI-H mCRPC, pembrolizumab. PSMA radionuclide therapy.

aPC stage - Biochemical recurrence^2,4
How to determine prognosis
Counsel patients of the risk of developing metastatic disease. Continue PSA measurements and clinical evaluations. Consider radiographic assessments based on overall PSA and PSA kinetics. If PSADT <12 months, perform periodic staging evaluations consisting of cross-sectional imaging such as CT or MRI and technetium bone scan and/or PSMA-PET.
Treatments available
If no metastatic disease is shown on imaging, observe or offer clinical trial enrollment. ADT and enzalutamide for patients with high-risk biochemical recurrence.

aPC stage - mCSPC²
How to determine prognosis
Assess the extent of metastatic disease (low vs high volume)—high-volume is defined as ≥4 bone metastases with at least one metastasis outside of the spine/pelvis and/or the presence of visceral metastases. Assess if newly diagnosed mCSPC patient is experiencing symptoms from metastatic disease at time of presentation to guide discussions of prognosis and further disease management. Obtain baseline PSA and serial PSA at 3-to-6-month intervals after initiation of ADT and consider periodic conventional imaging. Offer genetic testing.
Treatments available
ADT with GnRH agonists or antagonists or surgical castration. ADT in combination with either ARPI (abiraterone acetate plus prednisone, apalutamide, enzalutamide) or chemotherapy (docetaxel). In patients with de novo mCSPC, ADT in combination with docetaxel and either abiraterone acetate plus prednisone or darolutamide. In mCSPC patients with low-volume metastatic disease, primary radiotherapy to the prostate in combination with ADT. Do not offer bicalutamide, flutamide, or nilutamide in combination with GnRH agonists, except to block T flares. Do not offer oral ARPI without ADT.

aPC stage - nmCRPC²
How to determine prognosis
Obtain serial PSA measurements at 3-to-6-month intervals. Calculate a PSADT starting at the time of development of castration resistance. Assess patients for development of metastatic disease using conventional or PSMA-PET imaging at intervals of 6-to-12 months.
Treatments available
Apalutamide, darolutamide, and enzalutamide with continued ADT for those at high risk for developing metastatic disease (PSADT ≤10 months). Observe those with continued ADT who are at lower risk (PSADT >10 months) for developing metastatic disease. Do not offer systemic chemotherapy or immunotherapy outside of a clinical trial.

aPC stage - mCRPC^2,15,16
How to determine prognosis
Obtain baseline labs (eg, PSA, testosterone, LDH, Hgb, alkaline phosphatase level) and review location of metastatic disease (lymph node, bone, visceral), disease-related symptoms, and PS to inform discussions of prognosis and treatment decision-making. In mCRPC patients without PSA progression or new symptoms, perform imaging at least annually. In mCRPC patients with disease progression (PSA or radiographic progression or new disease-related symptoms) having previously received docetaxel and androgen pathway inhibitor, who are considering Lu-PSMA-617, order PSMA-PET imaging. Offer genetic testing.
Treatments available
In newly diagnosed mCRPC patients who have not received prior ARPIs, continue ADT with abiraterone acetate plus prednisone, docetaxel, or enzalutamide. If one ARPI fails, it is possible to use another, but it may also be more likely to fail Sipuleucel-T before chemotherapy in patients who are asymptomatic or minimally symptomatic. Radium-223 for patients with painful bone metastases and without known visceral disease or lymphadenopathy. Lutetium-PSMA-617 (Lu-PSMA-617) in patients who have received docetaxel and ARPI and have cancer visible on PSMA-PET. Taxane chemotherapy given with prednisone (docetaxel and cabazitaxel). For patients who received prior docetaxel with or without prior abiraterone acetate plus prednisone or enzalutamide for CRPC, offer cabazitaxel PARP inhibitors for patients with deleterious or suspected deleterious germline or somatic HRR gene-mutated mCRPC following prior treatment with enzalutamide or abiraterone acetate and/or a taxane-based chemotherapy. Platinum-based chemotherapy such as carboplatin for those who cannot use or obtain a PARPi For patients with MMR deficient or MSI-H mCRPC, pembrolizumab. PSMA radionuclide therapy. s.

Later-line treatment considerations

For patients who have exhausted all therapeutic options, consider platinum chemotherapy or pembrolizumab if the cancer has mutations that lead to mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H).²

Bone protective agents such as denosumab and zoledronic acid can be used to maintain bone health while on aPC treatment.²

Knowing which treatments to use for your patients’ aPC type and what they have been on previously can help determine next steps in treatment decision-making—it's important to be aware of all options that can be utilized before offering the option of clinical trial participation.

Importance of collaborating with other medical specialties during treatment

Advanced prostate cancer treatment can be complex and cause numerous side effects. It’s important to provide patients with comprehensive care by ensuring they have coordinated care between a team of physicians such as urologists, oncologists, primary care physicians, cardiologists, dietitians, physical therapists, social workers, psychologists, and more.²

Working directly as a multidisciplinary team allows elevated care for patients. Having trusted multidisciplinary HCPs available during treatment can allow you firsthand insight into how the patient’s disease is progressing, how treatment is working, and what side effects they need assistance with.

The Prostate Cancer 360 initiative

The Prostate Cancer 360 (PC360) initiative was created by a team of 14 interdisciplinary experts who have a dedicated clinical interest in prostate cancer and ADT management. The group consists of¹⁷:

Urologists
Oncologists
Primary care physicians
Cardiometabolic physicians
Oncology nurses
Psychology, nutrition, and exercise experts
Prostate cancer patient representatives

These experts worked together to define challenges associated with ADT adverse event management and developed recommendations for ADT prescribers so they can provide better care to patients.¹⁷

Since ADT is a foundational therapy for advanced prostate cancer, the PC360 recommendations should be considered during continued treatment for aPC.

Learn more about PC360 at ProstateCancer360.com.

Treatment planning foradvanced prostate cancer (aPC)

Therapy in aPC aims to extend life, prevent complications, and maintain quality of life and performance status1

It’s critical to take performance status (PS) and predicted life expectancy into account when conducting clinical decision-making for aPC1,2