In the United States, prostate cancer is the most frequent cancer diagnosed in men and the second most common cause of cancer fatalities.¹ Approximately 288,300 men are diagnosed with the disease annually, and prostate cancer is responsible for 34,700 deaths each year.¹ The median age at diagnosis of prostate cancer is 66 years.¹

Most prostate cancers are found early and are asymptomatic. If symptoms are present, patients may experience blood in urine or semen, back pain, or erectile dysfunction.² 

Although the 5-year survival rate for patients with nonadvanced prostate cancer is 99% in the United States, the course of treatment is not always clear, and there is much debate over which strategies are most effective for prostate cancer in the long term.³

Staging, Risk, and Diagnosis of Prostate Cancer

Because of its prevalence, prostate cancer is highly screened for in men. Diagnosis is made through a combined approach. Imaging via magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) is routinely performed. Serum prostate-specific antigen (PSA) levels and digital rectal examination are relatively noninvasive diagnostic procedures that are often performed. Transrectal and transperineal biopsy of the tumor, as well as transurethral resection of the prostate, may be performed to determine the size and histologic grade of a tumor.⁴

Proper staging of prostate cancer depends on 5 critical characteristics:

• Tumor size and spread to neighboring organs (T);
• Spread of tumor to lymph nodes (N);
• Metastasis or spread to distant lymph nodes, bone, or distant organs (M);
• Histologic grade of the tumor, based on the Gleason score; and
• PSA levels at the time of diagnosis.⁵

T stages for prostate cancer can be determined clinically (cT) or pathologically (pT). Biopsy or resection is required for pT staging. T stages for prostate cancer range from 1 to 4 based on spread of the tumor. N stages for prostate cancer are binary: 0 denotes no spread to regional lymph nodes, and 1 indicates that the tumor has spread. M0 indicates no metastasis, M1a indicates distant lymph node metastasis, M1b indicates bone metastasis, and M1c indicates metastasis to distant organs. The highest Gleason score is 10, which signifies a poorly differentiated tumor. Histologic grade also includes Gleason pattern, and these grades range from 1 to 5, with 5 having the worst patterning and least differentiation. Lastly, PSA values correlate weakly with prognosis. A higher PSA value can indicate a higher likelihood of tumor metastasis.

Stage I: Tumor is cT1-2 or pT2 with no lymph node involvement or metastasis (N0, M0). Gleason score is less than 6, and PSA is less than 10. Note that pT2 is the lowest pT classification for prostate cancer. 

 Stage II: Tumor is T1-T2 with no lymph node involvement or metastasis (N0, M0). Gleason score could be up to 8, and PSA is less than 20.

Stage III: Tumor may not have spread extensively (T1-2) with Gleason score less than 6 and PSA greater than 20, or tumor has spread extensively (T3-4) with Gleason score up to 8, or Gleason score is up to 10. There is no lymph node involvement or metastasis (N0, M0).

Stage IV: Tumor could be at any stage with 1 lymph node metastasis (N1) and no subsequent metastasis (M0) with Gleason score up to 10, or metastasis (M1) with any combination of tumor spread, lymph node involvement, PSA, and Gleason score.

Relative individual health risks such as age, medical history, and family history also play a role in determining how prostate cancer is typically treated.^3,6 Treatment recommendations are often determined by relative risk or metastatic disease stage rather than stage exclusively. These categories include:

• Very low risk
• Low risk
• Intermediate risk
• High risk
• Very high risk
• Stage IVa
• Stage IVb

Prostate Cancer Treatment Types

Most therapies for early stages of prostate cancer involve either surgically removing the tumor or active surveillance. Because many prostate cancers require testosterone to grow, hormonal therapies aimed at reducing the amount of testosterone are frequently used in addition to medical procedures. Castration-resistant prostate cancer (CRPC) refers to tumors that continue to grow in the absence of testosterone. Chemotherapy, immunotherapy, and radio-ligand targeted therapy can be used for CRPC or aggressive and recurrent disease.⁴

Chemotherapy

Chemotherapy in prostate cancer is only used for metastatic (stage IVb) CRPC, and it is delivered systemically. The following are approved chemotherapy agents for the treatment and management of prostate cancer⁷:

• Cabazitaxel
• Carboplatin
• Docetaxel
• Mitoxantrone hydrochloride

Immunotherapy

Immunotherapy in prostate cancer is only recommended in stage IV, metastatic CRPC or recurrent disease. The following are approved immunotherapy agents for use in prostate cancer:^3,7

• Pembrolizumab
• Sipuleucel-T

Targeted Therapy

Targeted therapy can be useful for prostate cancer when the patient has specific mutations, the tumor expresses unique molecular characteristics, or the cancer has metastasized in a specific way. Individuals with homologous recombination repair gene mutations (HRRm) respond better to certain therapies, such as olaparib. A specific gene that often has HRRm is BRCA. Rucaparib can be used in individuals with specific BRCA mutations. Tumors expressing prostate-specific membrane antigens may be good candidates for lutetium. Patients with bone metastases would be appropriate candidates for treatment with radioligands such as radium 223. Overall, these therapies are predominantly used in metastatic CRPC. The following are approved targeted therapies for use in prostate cancer3-7:

• Lutetium lu 177 vipivotide tetraxetan
• Olaparib
• Radium 223 dichloride
• Rucaparib camsylate

Hormonal Therapy

Broadly, hormonal therapy either blocks or bolsters male and female sex hormones. In prostate cancer, the overall goal of hormonal therapy is to reduce testosterone, which is required for tumor growth. These can be given in combination with radiation treatment (RT), surgical/procedural manipulations, or on their own. The following are approved therapies for use in prostate cancer that work on a patient’s hormonal system^3,7:

• Abiraterone acetate 
• Apalutamide
• Bicalutamide
• Darolutamide
• Degarelix
• Enzalutamide
• Flutamide
• Goserelin acetate
• Leuprolide acetate
• Nilutamide
• Relugolix

When and How to Use Different Treatments for Prostate Cancer

Chemotherapy agents are generally given systemically via intravenous infusion during stage IVb CRPC. The following table reviews dosage and recommended use of chemotherapy for prostate cancer.

Table 1. Management Guidelines for Chemotherapy for Prostate Cancer

Drug	Dose	Administration	Treatment Duration	Recommended Use
Cabazitaxel	20 mg/m2 with oral prednisone 10 mg	IV infusion over 1 h	Every 3 wk	Stage IVb CRPC; second-line
Carboplatin*	AUC 2 or AUC 5; administered with paclitaxel	IV infusion	Every wk for 5 wk	Stage IVb CRPC; second-line
Docetaxel	75 mg/m2 with oral prednisone 5 mg twice daily	IV infusion over 1 h	Every 3 wk	Stage IVb CRPC; first-line
Mitoxantrone hydrochloride	12 to 14 mg/m2	IV infusion	Every 3 wk	Stage IVb; palliative care for metastatic castration-resistant adenocarcinomas

CRPC = castration-resistant prostate cancer; IV = intravenous.

*Carboplatin is not an FDA-approved drug for prostate cancer, but it is recommended by the NCCN.

From FDA-approved prescribing information and NCCN.^3,7-11

Immunotherapy agents for prostate cancer are primarily given for metastatic, castration-resistant disease where other therapies have already been employed. The following table reviews the dosage and recommended use for approved immunotherapy agents for prostate cancer.

Table 2. Management Guidelines for Immunotherapy for Prostate Cancer

Drug	Dosage	Administration	Recommended Use
Pembrolizumab*	200 mg every 3 wk or 400 mg every 6 wk	IV infusion	Stage IVb CRPC and used only if the patient has experienced disease progression with docetaxel and hormone therapy
Sipuleucel-T	50 million autologous CD54+ cells activated with PAP or GM-CSF, 3 complete doses given every 2 wk	IV infusion over 60 min	Stage IV CRPC

CRPC = castration-resistant prostate cancer; GM-CSF = granulocyte-macrophage colony-stimulating factor; IV = intravenous; PAP = prostatic acid phosphatase.

*Pembrolizumab was not listed on FDA-approved drugs for prostate cancer but it is recommended by NCCN.

From FDA-approved prescribing information and NCCN.^3,12-13

Targeted therapy agents are used primarily for metastatic CRPC with the tumor displaying certain molecular characteristics or specific spread, or if the patient has specific mutations. The following table reviews the dosage and recommended use for approved targeted therapies for prostate cancer.

Table 3. Management Guidelines for Targeted Therapy for Prostate Cancer

Drug	Dose	Administration	Treatment Duration	Recommended Use
Lutetium lu 177 vipivotide tetraxetan	1000 MBq/mL	Injection	Every 6 wk for up to 6 doses or until disease worsens or intolerable toxicity	PSMA-positive, stage IVb CRPC
Olaparib	300 mg twice daily	Oral tablets	Until disease worsens or intolerable toxicity	HRR mutation, stage IV CRPC with progression following treatment with enzalutamide or abiraterone
Radium 223 dichloride	1100 kBq/mL	Injection	Every 4 wk up to 6 doses	Stage IVb CRPC with bone metastasis and no visceral metastasis
Rucaparib camsylate	600 mg twice daily with GnRH therapy or bilateral orchiectomy	Oral tablets	Until disease worsens or intolerable toxicity	BRCA mutation and stage IVb CRPC; second-line therapy after hormonal treatment has been used

CRPC = castration-resistant prostate cancer; GnRH = gonadotropin-releasing hormone; HRR = homologous recombination repair; IV= intravenous; PSMA = prostate-specific membrane antigen.

From FDA-approved prescribing information and NCCN. ^3,14-17

Hormonal therapy agents are the first-line treatment for prostate cancer, but they can also be used in advanced, castration-resistant disease. The following table reviews the dosage and recommended use for approved hormonal therapies for prostate cancer.

Table 4. Management Guidelines for Hormonal Therapy for Prostate Cancer

Drug	Dose	Administration	Treatment Duration	Recommended Use
Abiraterone acetate	1000 mg orally once daily with prednisone 5 mg once or twice daily with either GnRH therapy or bilateral orchiectomy	Oral tablets	2 y	Stage IVa CRPC and castration-sensitive prostate cancer
Apalutamide	240 mg daily with GnRH therapy	Oral tablets	2 y	Very-high-risk disease, stage IVa and IVb metastatic castration-sensitive prostate cancer, CRPC
Bicalutamide	50 mg daily with LHRH therapy	Oral tablets	4-6 mo or 1-3 y	Intermediate risk, high risk, very high risk, stage IVa and IVb
Darolutamide	300 mg twice daily; taken with docetaxel in metastatic disease	Oral tablets	4-6 mo or 1-3 y	Nonmetastatic CRPC, metastatic castration-sensitive prostate cancer, stage IVb
Degarelix	120 mg twice daily as starting dose followed by 80 mg	SC injection in the abdomen	Every 28 d for 4-6 mo or 1-3 y	Intermediate risk, high risk, very high risk, stage IVa and IVb
Enzalutamide	160 mg daily with either concurrent GnRH therapy or bilateral orchiectomy	Oral tablets	Until disease worsens or intolerable toxicity	Stage IV metastatic CRPC and castration-sensitive prostate cancer
Flutamide	250 mg taken 3 times daily 8 h apart with RT or LNRH therapy	Oral tablets	4-6 mo or 1-3 y	Intermediate risk, high risk, very high risk, stage IVa and IVb
Goserelin acetate	3.6 mg	SC injection	Every 28 d for 4-6 mo or 1-3 y	Intermediate risk, high risk, very high risk, stage IVa and IVb
Leuprolide acetate	7.5 mg monthly; 22.5 mg every 3 mo; 30 mg every 4 mo; 45 mg every 6 mo	SC injection in the abdomen	Monthly, every 3 mo, every 4 mo, or every 6 mo for 4-6 mo or 1-3 y	Intermediate risk, high risk, very high risk, stage IVa and IVb
Nilutamide	300 mg once daily for 30 days followed by 150 mg once daily afterward	Oral tablets	Daily for 30 d for 4-6 mo or 1-3 y	Intermediate risk, high risk, very high risk, stage IVa and IVb
Relugolix	360 mg on day 1 followed by 120 mg taken daily	Oral tablets	4-6 mo or 1-3 y	Intermediate risk, high risk, very high risk, stage IVa and IVb

CRPC = castration-resistant prostate cancer; GnRH = gonadotropin-releasing hormone; IV = intravenous; LHRH = luteinizing hormone-releasing hormone; RT = radiation treatment; SC = subcutaneous.

From FDA-approved prescribing information. ^3,18-28

Monitoring Side Effects of Prostate Cancer

Therapies for prostate cancer tend to have similar side effect profiles based on their category. Prostate cancer only affects men, so direct harm to the fetus or to an infant through breastfeeding is not relevant. Note has been made for cases where the sperm of the individual undergoing therapy could cause risk to a new fetus or could cause infertility.

Chemotherapy broadly works by damaging the DNA of fast-growing cells. These therapies tend to have side effects on other cells that happen to grow quickly, such as hair cells and nail cells. Chemotherapy agents are processed through the liver and kidney and put stress on those organs. They also often have gastrointestinal side effects.

Table 5. Side Effect Profiles for Chemotherapy for Prostate Cancer

Drug	Most Common Adverse Events	Side Effects Necessitating Treatment Discontinuation or Modification	Drug-Drug Interactions	Special Populations
Cabazitaxel	Reduced neutrophils, anemia, diarrhea, nausea, tiredness, weakness, vomiting, hematuria, constipation, reduced hunger, back pain, stomach pain	Reduced neutrophils, allergic reactions, GI disorders, kidney failure, bladder inflammation, respiratory disorders, liver impairment	CYP3A inhibitors	Could cause risk to fetus, so male patients are advised to use contraception for 3 mo after last dose; may cause infertility; geriatric patients may have more adverse events; close monitoring of patients with pre-existing kidney and liver impairment
Carboplatin	Low platelet count, low neutrophil count, low leukocyte count, anemia, nausea, vomiting, neurotoxicity, increase alkaline phosphatase, decreased magnesium, weakness, general pain	Low platelet count, low neutrophil count, low leukocyte count, low red blood cell count	Use with caution with nephrotoxic drugs	Could cause harm to fetus
Docetaxel	Anemia, reduced neutrophils, infection, fluid retention, swelling, sensory nerve damage, hair loss, nail changes, nausea, diarrhea, mouth inflammation, taste disturbances, vomiting, weight loss, cough, labored breathing, left ventricular dysfunction, tiredness, muscle weakness	Secondary cancers, severe skin reactions, neurologic disorders, eye disorders, severe weakness, alcohol consumption	Cytochrome P450 3A4 inducers, inhibitors, and substrates	Could cause harm to fetus so male patients should use contraception for 3 mo following treatment; may cause infertility in male patients; greater likelihood of liver, kidney, and heart complications in geriatric population; not recommended for patients with liver disease
Mitoxantrone hydrochloride	Nausea, tiredness, hair loss, weight loss, constipation, labored breathing, nail changes, swelling, mouth inflammation, cardiac dysfunction	Bone marrow suppression, severe cardiac events	None indicated;  however, it may weakly induce CYP450 2E1 activity	Could cause harm to fetus; may not be recommended for patients with cardiac dysfunction

GI = gastrointestinal.

From FDA-approved prescribing information and NCCN.^3,7-11

Immunotherapy agents typically trigger the immune system, which can result in hypersensitive, allergic reactions such as rashes or more serious cases such as anaphylaxis. Immune reactions can also result in patients feeling tired and in pain. Certain liver enzymes, such as aspartate aminotransferase, can also be affected.

Table 6. Side Effect Profiles for Immunotherapy for Prostate Cancer

Drug	Most Common Adverse Events	Side Effects Necessitating Treatment Discontinuation or Modification	Drug-Drug Interactions	Special Populations
Pembrolizumab	Tiredness, musculoskeletal pain, itchy skin, rash, nausea, weight loss, reduced hunger, hyperglycemia, anemia, decreased lymphocytes, low levels of albumin, low serum sodium levels, increased alkaline phosphatase levels, increased creatinine levels, decreased phosphate levels, elevated AST levels, increased potassium levels, low serum calcium levels	Lung inflammation, infection of the colon, liver inflammation, adrenal insufficiency, inflammation of the pituitary gland, thyroiditis, overactive thyroid, type 1 diabetes, kidney disease,  underactive thyroid, skin rash, infusion-related reactions, reactions to stem-cell transplantation	None indicated	Could cause harm to fetus
Sipuleucel-T	Tiredness, chills, fever, joint pain, back pain, nausea, headache	Infusion-related reaction, blood clots, sepsis, infections	None indicated	Close monitoring of individuals taking immunosuppressants

AST = aspartate aminotransferase.

From FDA-approved prescribing information and NCCN.^3,12-13

Because targeted therapies work on unique molecular pathways, their side effects vary. In prostate cancer, the approved targeted therapies often lead to reductions in certain cell types, such as neutrophils, lymphocytes, platelets, and leukocytes. Myelodysplastic syndrome/acute myeloid leukemia are syndromes that result in immature blood cells.²⁹ Venous thromboembolic events are blood clots in veins.³⁰ Alanine aminotransferase and aspartate aminotransferase are liver enzymes that can be affected in patients undergoing treatment with targeted therapies.

Table 7. Side Effect Profiles for Targeted Therapy for Prostate Cancer

Drug	Most Common Adverse Events	Side Effects Necessitating Treatment Discontinuation or Modification	Drug-Drug Interactions	Special Populations
Lutetium lu 177 vipivotide tetraxetan	Tiredness, anemia, dry mouth, nausea, reduced hunger, constipation, reduced sodium, reduced lymphocyte count, reduced hemoglobin, reduced leukocyte count, reduced platelet count, reduced calcium	Reduced blood counts, reduced kidney function	None indicated	Could cause harm to fetus so male patients should use contraception for 14 wk following treatment; may cause infertility in male patients; more severe adverse events possible in geriatric population
Olaparib	Anemia, blood clots, nausea, diarrhea, vomiting, tiredness, decreased hunger, cough, labored breathing, reduced hemoglobin, reduced lymphocyte count, reduced leukocyte count, reduced neutrophil counts	Anemia, blood clots, lung inflammation, MDS/AML, VTE	Strong or moderate CYP3A inhibitors and inducers	Could cause harm to fetus so male patients should use contraception for 3 mo following treatment
Radium 223 dichloride	Nausea, vomiting, diarrhea, swelling in hands and feet, anemia, reduced lymphocyte, reduced leukocytes, reduced neutrophils, reduced platelets	Bone marrow suppression	None indicated	Could cause harm to fetus so male patients should use contraception for 6 mo following treatment; may cause infertility in male patients
Rucaparib camsylate	Tiredness, anemia, nausea, increased ALT/AST, reduced hunger, rash, constipation, vomiting, diarrhea, reduced platelets	MDS/AML	CYP1A2, CYP3A, CYP2C9, and CYP2C19 substrates	Could cause harm to fetus so male patients should use contraception for 3 mo following treatment

ALT = alanine aminotransferase; AML = acute myeloid leukemia;  AST = aspartate aminotransferase; MDS = myelodysplastic syndrome, VTE = venous thromboembolism.

From FDA-approved prescribing information and NCCN. ^3,14-17

Hormonal therapy for prostate cancer can affect liver enzyme levels. Hot flashes are a common symptom. In rare cases, there are more serious symptoms such as severe skin reactions, changes in heartbeat, and neurologic effects.

Table 8. Side Effect Profiles for Hormonal Therapy for Prostate Cancer

Drug	Most Common Adverse Events (>10%)	Side Effects Necessitating Treatment Discontinuation or Modification	Drug-Drug Interactions	Special Populations
Abiraterone acetate	Tiredness, joint pain, hypertension, nausea, swelling, low potassium, hot flashes, diarrhea, vomiting, upper respiratory tract infection, cough, headache, anemia, increased alkaline phosphatase levels, increased triglycerides, low white blood cell count, high cholesterol, high blood sugar	High serum sodium levels, adrenocortical insufficiency, liver toxicity, bone fractures, hypoglycemia	CYP3A4 inducers and CYP2D6 substrates	Could cause risk to the fetus, so male patients are advised to use contraception for 3 wk after last dose; may cause infertility in male patients; not recommended in patients with liver failure
Apalutamide	Tiredness, joint pain, skin rash, decreased hunger, falling, weight loss, high blood pressure, hot flashes, diarrhea, bone breaks	Cerebrovascular disorders and ischemia, bone fractures, seizures, SCARs	CYP3A4, CYP2C9, CYP2C19, UGT, P-gp, BCRP, and OATP1B1 substrates	Could cause risk to the fetus, so male patients are advised to use contraception for 3 mo after last dose; may cause infertility in male patients; because of fall risk, more dangerous for geriatric population
Bicalutamide	Hot flashes, general pain, back pain, stomach pain, pelvic pain, weakness, constipation,  infection, nausea, swelling of the hands of feet, anemia, labored breathing, diarrhea, blood in urine, urination urgency at night, growth and pain in breast tissue	Liver injury, hemorrhage	CYP3A4 substrates	Male patients are advised to use contraception for 130 days after last dose; may cause infertility in male patients
Darolutamide	Anemia, hyperglycemia, reduced lymphocyte count, reduced neutrophil count, elevated AST, elevated ALT, reduced calcium, elevated bilirubin, tiredness, pain in hands and feet, rash, weight gain, hypertension	Ischemia, seizure	P-gp with moderate or strong CYP3A inducers, P-gp with strong CYP3S inhibitors, BCRP substrates, OATP1T1 and OATP1B3 substrates	Male patients are advised to use contraception for 1 wk after last dose; may cause infertility in male patients; dose reduction recommended in patients with liver impairments
Degarelix	Injection site reactions, hot flashes, elevated transaminases, elevated GGT	Anaphylaxis or other hypersensitive reaction, QT-interval prolongation	None indicated	May cause infertility in male patients; patients with liver and kidney impairments should be closely monitored
Enzalutamide	Weakness, tiredness, back pain, hot flashes, constipation, joint pain, reduced hunger, diarrhea, hypertension	Seizure, PRES, anaphylaxis, ischemia, bone fractures	Strong CYP2C8 inhibitors, strong CYP3A4 inducers, CYP3A4, CYP2C9, and CYP2C19 substrates	Male patients are advised to use contraception for 3 mo after last dose; may cause infertility in male patients
Flutamide	Hot flashes, loss of libido, impotence, diarrhea, growth and pain of breast tissue	Liver injury, jaundice, increased ALT	Anticoagulants such as warfarin	Reduces sperm count
Goserelin acetate	Hot flashes, sexual dysfunction, UTI symptoms, tiredness	Tumor flare, hyperglycemia, diabetes, cardiovascular disease, elevated calcium, anaphylaxis, QT-interval changes, hemorrhage	None indicated	Could cause risk fetus, but no guidance given to male users
Leuprolide acetate	Feeling unwell, tiredness, hot flashes, testicular shrinking	Tumor flare, hyperglycemia, diabetes, cardiovascular disease, elevated calcium, anaphylaxis, QT-interval changes, hemorrhage, seizure	None indicated	Could cause risk to the fetus; may cause infertility in male patients
Nilutamide	Hot flashes, impaired adaptation to darkness	ILD, severe liver dysfunction	Drugs that require cytochrome P450 isoenzymes, drugs with low therapeutic margin such as vitamin K antagonists, theophylline, and phenytoin	Not indicated
Relugolix	Hot flashes, hyperglycemia, elevated triglycerides, musculoskeletal pain, reduced hemoglobin, elevated ALT, tiredness, elevated AST, constipation, diarrhea	QT-interval prolongation, anaphylaxis	P-gp inhibitors, P-gp and strong CYP3A inducers combined	Could cause risk to the fetus, so male patients are advised to use contraception for 2 wk after last dose; may cause infertility in male patients

ALT = alanine transferase; AST = aspartate transaminase; BCRP = breast cancer resistance protein; GGT = gamma-glutamyl transferase; ILD = interstitial lung disease; P-gp = P-glycoprotein; PRES = posterior reversible encephalopathy syndrome; UTI = urinary tract infection; SCARs = severe cutaneous adverse reactions; UGT = uridine diphosphate- glucuronosyltransferase.

From FDA-approved prescribing information and NCCN.^3,18-28

Guidelines for the Management of Prostate Cancer

The National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS) provide treatment recommendations for prostate cancer based on risk group and stage; therefore, the subsequent guidelines will be presented in the same manner.^3,6

Very Low Risk

Active surveillance is the preferred strategy for patients with very-low-risk prostate cancer. Surveillance includes regular examinations by the patient’s physician to ensure the cancer has not progressed. In some cases a patient may opt for radiation treatments that include external-beam radiation therapy (EBRT) or brachytherapy. Radical prostatectomy, a surgical procedure to remove the entire prostate, is also sometimes chosen.

Low Risk

Active surveillance is also the preferred strategy for patients with low-risk prostate cancer. The same radiation and surgical options as for very-low-risk prostate cancer may also be chosen. 

Intermediate Risk

The same treatment options exist in this broad group as in the lower-risk groups; however, hormonal therapy is also often recommended at this stage.

If the patient has a life expectancy of more than 10 years, active surveillance, radiation, or radical prostatectomy with pelvic lymph node dissection (PLND) are all treatment options. If the patient undergoes radical prostatectomy, additional treatment involves PSA monitoring or EBRT with or without hormonal treatment. If the patient receives hormonal therapy with radiation, treatment options are:

• Luteinizing hormone-releasing hormone (LHRH) agonists, which include goserelin, leuprolide, or triptorelin;
• LHRH agonist with the following antiandrogens: nilutamide, flutamide, or bicalutamide; or
• LHRH antagonists such as degarelix or relugolix.

If there is a regional lymph node (N1) affected, the above hormonal therapy is recommended without radiation.

If the tumor is considered higher risk due to higher pathologic grade or a greater number of positive biopsy cores, EBRT with hormonal therapy or EBRT with brachytherapy with or without hormonal therapy may be used without radical prostatectomy. In these cases, hormonal therapy regimens are the same as above but recommended specifically for 4 to 6 months.

If the patient has a life expectancy of 5 to 10 years, observation is preferred.

High Risk or Very High Risk

If the patient has a life expectancy of more than 5 years and they are symptomatic, a combination of EBRT and the above hormonal therapy is recommended. Patients receiving EBRT and hormonal therapy alone receive hormonal therapy for 1.5 to 3 years. Patients receiving EBRT with brachytherapy and hormonal therapy can receive hormonal therapy for 1 to 3 years.

These patients may instead opt for radical prostatectomy with PLND followed by either EBRT with or without hormonal therapy or monitoring.

Patients with very-high-risk prostate cancer are recommended to have EBRT with 2 years of hormonal therapy with the addition of abiraterone.

Patients with less than a 5-year prognosis and who are asymptomatic can opt for observation, hormonal therapy alone, or EBRT alone.

Stage IVa

Symptomatic patients with a prognosis greater than 5 years should receive EBRT with hormonal therapy and abiraterone.

Patients with less than a 5-year prognosis and who are asymptomatic can opt for observation or hormonal therapy alone.

Stage IVb/Metastatic Disease

Treatment at this stage is based on whether the tumor is castration sensitive or castration resistant.

Castration Sensitive

Hormonal therapy is recommended with either abiraterone, apalutamide, or enzalutamide. Hormonal therapy may also be given with docetaxel and either abiraterone or darolutamide. There are some cases where hormonal therapy with or without EBRT may also be used.

Castration Resistant

At this time, hormonal therapy or therapy with denosumab may be recommended. If the cancer is a small cell/neuroendocrine prostate cancer, systemic chemotherapy is recommended.

For adenocarcinomas, recommendations are made based on previous treatments.

If the patient has not had docetaxel or prior hormone therapy:

• Abiraterone, docetaxel, or enzalutamide are preferred;
• If they have bone metastasis, radium-223 is recommended; and
• Sipuleucel-T may also be recommended here.

If the patient has received docetaxel but not prior hormone therapy:

• Abiraterone, cabazitaxel, or enzalutamide are preferred;
• Cabazitaxel/carboplatin may be used; and
• Mitoxantrone may be used as palliative care for symptomatic patients.

If the patient has received hormone therapy without docetaxel:

• Docetaxel is preferred;
• Rucaparib or olaparib may be used in patients with certain mutations; and
• Cabazitaxel/carboplatin may be used.

If the patient has received previous hormone therapy and docetaxel:

• Lutetium lu 177 vipivotide is used if the tumor has certain molecular characteristics;
• Cabazitaxel is preferred systemic chemotherapy;
• Cabazitaxel/carboplatin may be used;
• Rucaparib or olaparib may be used in patients with certain mutations; and
• Pembrolizumab may be used for certain tumors that have certain molecular characteristics.

For any metastatic adenocarcinoma, if there is bone metastasis, radium-223 is recommended. Sipuleucel-T may also be recommended for any adenocarcinoma.

Castration-Resistant Prostate Cancer Without Metastasis

If the time it takes for PSA to double is greater than 10 months, monitoring of cancer is preferred.

If the time it takes for PSA to double is less than 10 months, apalutamide, enzalutamide, or darolutamide regimens are preferred.^3,6

References

1. Key statistics for prostate cancer. American Cancer Society. Updated January 12, 2023. Accessed May 18, 2023.

2. Signs and symptoms of prostate cancer. American Cancer Society. Updated August 1, 2019. Accessed May 19, 2023.

3. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^Ⓡ), Prostate Cancer. National Comprehensive Cancer Network. Updated September 16, 2022. Accessed May 16, 2023.

4. Prostate Cancer Treatment (PDQ®)–Health Professional Version. National Cancer Institute. Updated February 13, 2023. Accessed May 17, 2023.

5. Prostate cancer stages. American Cancer Society. Updated October 8, 2021. Accessed May 18, 2023.

6. Initial treatment of prostate cancer, by stage risk group. American Cancer Society. Updated August 9, 2022. Accessed May 19, 2023.

7. Drugs approved for prostate cancer. National Cancer Institute. Updated May 4, 2022. Accessed May 16, 2023.

8. Jevtana. Drug Label Information. DailyMed. Updated February 25, 2 021. Accessed May 17, 2023.

9. Carboplatin. Drug Label Information. DailyMed. Updated July 7, 2021. Accessed May 17, 2023.

10. Docetaxel. Drug Label Information. DailyMed. Updated October 18, 2022. Accessed May 17, 2023.

11. Mitoxantrone. Drug Label Information. DailyMed. Updated December  31, 2019. Accessed May 17, 2023.

12. Keytruda. Drug Label Information. DailyMed. Updated April 3, 2023. Accessed May 17, 2023. 

13. Provenge. Drug Label Information. DailyMed. Updated December 9, 2021. Accessed May 17, 2023.

14. Pluvicto. Drug Label Information. DailyMed. Updated April 20, 2023. Accessed May 17, 2023.

15. Lynparza. Drug Label Information.  DailyMed. Updated October 27, 2022. Accessed May 17, 2023.

16. Xofigo. Drug Label Information. DailyMed. Updated December 10, 2019. Accessed May 17, 2023.

17. Rubraca. Drug Label Information. DailyMed. Updated December 23, 2023. Accessed May 17, 2023.

18. Zytiga. Drug Label Information. DailyMed. Updated October 14, 2021. Accessed May 17, 2023.

19. Erleada. Drug Label Information.  DailyMed. Updated April 14, 2023. Accessed May 17, 2023.

20. Casodex. Drug Label Information. DailyMed. Updated October 1, 2019. Accessed May 17, 2023.

21. Nubeqa. Drug Label Information. DailyMed. Updated August 5, 2022. Accessed May 17, 2023.

22. Firmagon. Drug Label Information. DailyMed. Updated February 14, 2022. Accessed May 17, 2023.

23. Xtandi. Drug Label Information. DailyMed. Updated September 15, 2022. Accessed May 17, 2023.

24. Flutamide. Drug Label Information. DailyMed. Updated November 29, 2018. Accessed May 17, 2023.

25. Zoladex. Drug Label Information. DailyMed. Updated April 16, 2021. Accessed May 17, 2023.

26. Eligard. Drug Label Information. DailyMed. Updated January 9, 2023. Accessed May 17, 2023.

27. Nilandron. Drug Label Information.  DailyMed. Updated July 8, 2022. Accessed May 17, 2023.

28. Orgovyx. Drug Label Information. DailyMed. Updated April 4, 2023. Accessed May 17, 2023.

29. Klepin HD. Myelodysplastic syndromes and acute myeloid leukemia in the elderly. Clin Geriatr Med. 2016,32(1):155-173. doi:10.1016/j.cger.2015.08.010 

30. What is venous thromboembolism? National Heart, Lung, and Blood Institute. Updated September 19, 2022. Accessed May 19, 2023.

Author Bio

Hannah Actor-Engel, PhD, earned a BS in Neural Science at New York University and her PhD in Neuroscience at the University of Colorado. She is a multidisciplinary neuroscientist who is passionate about scientific communication and improving global health through biomedical research.