Adenocarcinoma of the prostate is the most common nondermatologic cancer in men > 50 in the United States. In the United States, it is estimated that about 288,300 new cases and about 34,700 deaths will occur in 2023 (1 General references Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more ). Incidence increases with each decade of life; autopsy studies show prostate cancer in 15 to 60% of men aged 60 to 90 years old, with incidence increasing with age. The lifetime risk of being diagnosed with prostate cancer is 1 in 6. Median age at diagnosis is 72, and > 60% of prostate cancers are diagnosed in men > 65 (1 General references Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more ). Risk is highest for Black men, in particular those from the Caribbean. Genetic risk factors include BRCA1/2 mutations, Lynch syndrome Lynch Syndrome Lynch syndrome is an autosomal dominant disorder responsible for 2 to 3% of cases of colorectal cancer ( 1). Symptoms, initial diagnosis, and treatment are similar to other forms of colorectal... read more , and family history of some hereditary breast and ovarian cancers.
Sarcoma of the prostate is rare, occurring primarily in children. Undifferentiated prostate cancer, squamous cell carcinoma, and ductal transitional carcinoma also occur infrequently. Prostatic intraepithelial neoplasia is considered a possible premalignant histologic change.
Hormonal influences contribute to the course of adenocarcinoma but almost certainly not to other types of prostate cancer. The effect of testosterone supplements on the risk of prostate cancer remains controversial. Data suggest that testosterone supplements for treatment of symptomatic hypogonadism do not increase the risk of prostate cancer (2 General references Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more ).
1. American Cancer Society, Cancer Statistics Center: Prostate at a glance. Accessed September 10, 2023.
2. Boyle P, Koechlin A, Bota M, et al: Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate-specific antigen (PSA) level: A meta-analysis. BJU Int 118(5):731-741, 2016. doi: 10.1111/bju.13417
Symptoms and Signs of Prostate Cancer
Prostate cancer usually progresses slowly and rarely causes symptoms until advanced. In advanced disease, hematuria and symptoms of bladder outlet obstruction Obstructive Uropathy Obstructive uropathy is structural or functional hindrance of normal urine flow, sometimes leading to renal dysfunction (obstructive nephropathy). Symptoms, less likely in chronic obstruction... read more (eg, straining, hesitancy, weak or intermittent urine stream, a sense of incomplete emptying, terminal dribbling) or ureteral obstruction (eg, renal colic, flank pain, renal dysfunction) may appear. Bone pain, pathologic fractures, or spinal cord compression may result from osteoblastic metastases to bone (commonly pelvis, ribs, vertebral bodies).
Diagnosis of Prostate Cancer
Screening by prostate-specific antigen Prostate-specific antigen (PSA) levels Benign prostatic hyperplasia (BPH) is nonmalignant adenomatous overgrowth of the periurethral prostate gland. Symptoms are those of bladder outlet obstruction—weak stream, hesitancy, urinary... read more (PSA) with or without a digital rectal examination (DRE)
Diagnosis by needle biopsy of the prostate (most common) or biopsy of metastatic lesion
Grading by histology
Staging by CT/MRI and bone scanning, possibly newer modalities such as prostate-specific membrane antigen (PSMA)–based PET-CT or using other PET agents
Sometimes stony-hard induration or nodules are palpable during DRE, but the examination is often normal; induration and nodularity suggest cancer but must be differentiated from granulomatous prostatitis, prostate calculi, and other prostate disorders. Extension of induration to the seminal vesicles and lateral fixation of the gland suggest locally advanced prostate cancer. Prostate cancers detected by DRE tend to be large, and > 50% extend through the capsule.
Diagnosis of prostate cancer requires histologic confirmation, most commonly by transrectal or transperineal ultrasound–guided needle biopsy, which can be done in an office with use of local anesthesia or in an operating room under sedation. Hypoechoic areas on ultrasound are more likely to represent cancer. Occasionally, prostate cancer is diagnosed incidentally in tissue removed during surgery for benign prostatic hyperplasia Benign Prostatic Hyperplasia (BPH) Benign prostatic hyperplasia (BPH) is nonmalignant adenomatous overgrowth of the periurethral prostate gland. Symptoms are those of bladder outlet obstruction—weak stream, hesitancy, urinary... read more (BPH). Multiparametric MRI can risk-stratify patients for the need for a biopsy and identify suspect areas that should be targeted. It is now commonly used before initial biopsy in or in men who are on active surveillance.
Most cancers today are found by screening with serum PSA levels (and sometimes DRE). Screening recommendations can vary, but screening is commonly done annually in men > 50 years old and is sometimes begun earlier for men at high risk (eg, those with a family history of prostate cancer, Black men). Screening is not usually recommended for men with a life expectancy < 10 to 15 years.
Abnormal findings are further investigated based on clinician and patient preferences. Multiparametric MRI can detect suspect lesions, and various urine and blood tests may help determine the need for prostate biopsy.
It is still not certain whether screening decreases morbidity; decreases in mortality appear likely (1 Diagnosis references Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more ), but the number needed to screen is high. It remains unclear if any gains resulting from screening outweigh the decreases in quality of life resulting from treatment of asymptomatic cancers. Screening is recommended by some professional organizations and discouraged by others. A pooled analysis of ERSPC (European Randomized Study of Screening for Prostate Cancer) and PLCO (Prostate, Lung, Colorectal, and Ovarian) trial data suggests that screening in both trials demonstrated a reduction in prostate cancer mortality when controlling for differences in screening intensity despite the high rate of contamination in the control arm of PLCO (2, 3 Diagnosis references Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more ). As a result, in 2017, the United States Preventive Services Task Force (USPSTF) reconsidered their 2012 recommendation against screening for prostate cancer (Level D) with a possible benefit (Level C) in men less than 70 years of age. Based on recent data (4 Diagnosis references Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more ), the decrease in prostate cancer-specific mortality associated with screening appears likely, but the number needed to screen is high.
The current USPSTF recommendation is that for men aged 55 to 69 years, the decision to undergo periodic prostate-specific antigen (PSA)–based screening for prostate cancer should be an individual one after discussing the potential benefits and harms of screening with a clinician (4 Diagnosis references Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more ). Most patients with newly diagnosed prostate cancers have a normal DRE, and serum PSA measurement is not ideal as a screening test. Although PSA is elevated in 25 to 92% of patients with prostate cancer (depending on tumor volume), it also is moderately elevated in 30 to 50% of patients with benign prostatic hyperplasia Benign Prostatic Hyperplasia (BPH) Benign prostatic hyperplasia (BPH) is nonmalignant adenomatous overgrowth of the periurethral prostate gland. Symptoms are those of bladder outlet obstruction—weak stream, hesitancy, urinary... read more (depending on prostate size and degree of obstruction), in some smokers, and for several weeks after prostatitis Prostatitis Prostatitis refers to a disparate group of prostate disorders that manifests with a combination of predominantly irritative or obstructive urinary symptoms and perineal pain. Some cases result... read more or prostate manipulation (catheter, cystoscopy, prostate biopsy). Rarely, other activities such as sexual activity or extreme bicycle riding falsely elevate PSA.
A level of ≥ 4 ng/mL (4 micrograms [mcg]/L) is often considered an indication for biopsy in men > 50 years old. Although very high levels are significant (suggesting extracapsular extension of the tumor or metastases) and likelihood of cancer increases with increasing PSA levels, there is no cut-off below which there is no risk.
In asymptomatic patients, positive predictive value for cancer is 67% for PSA > 10 ng/mL (10 mcg/L) and 25% for PSA 4 to 10 ng/mL (4 to 10 mcg/L); recent evidence indicates a 15% prevalence of cancer in men ≥ 55 years old with PSA < 4 ng/mL (4 mcg/L) and a 10% incidence with PSA between 0.6 and 1.0 ng/mL (0.6 and 1.0 mcg/L). However, cancer present in men with lower levels tends to be smaller and of lower grade, although high-grade cancer (Gleason score 7 to 10) can be present at any level of PSA; perhaps 15% of cancers manifesting with PSA < 4 ng/mL (4 mcg/L) are high grade. Although it appears that a cut-off of 4 ng/mL (4 mcg/L) will miss some potentially serious cancers, the cost and morbidity resulting from the increased number of biopsies necessary to find them are unclear.
The decision whether to biopsy may be helped by other PSA-related factors, even in the absence of a family history of prostate cancer. For example, the rate of change in PSA (PSA velocity) should be < 0.75 ng/mL/yr (0.75 mcg/L/yr; lower in younger patients). Biopsy is usually recommended for PSA velocities > 0.75 ng/mL/yr (0.75 mcg/L/yr). Similarly, PSA density (PSA relative to prostate volume) can help guide need for biopsy; biopsy should be considered if values are ≥ 0.15 (or sometimes ≥ 0.10 ng/mL).
Assays that determine the free-to-total PSA ratio and complex PSA are more tumor specific than standard total PSA measurements and may reduce the frequency of biopsies in patients without cancer. Prostate cancer is associated with less free PSA; no standard cut-off has been established, but generally, levels < 10 to 20% warrant biopsy. Other isoforms of PSA and new markers for prostate cancer are being studied. None of these other uses of PSA answers all of the concerns about possibly triggering too many biopsies. Many new tests (eg, urinary prostate cancer antigen 3 [PCA-3], Prostate Health Index, 4Kscore, urinary SelectMDX, and others) are available commercially and may be useful in screening decisions.
Clinicians should discuss the risks and benefits of PSA testing with patients. Some patients prefer to eradicate cancer at all costs—no matter how low the potential for progression and possible metastasis—and may prefer annual PSA testing. Others may value quality of life highly and can accept some uncertainty; they may prefer less frequent (or no) PSA testing.
Men with newly diagnosed prostate cancer should be offered germline testing and genetic counseling if they have intraductal histology, metastatic or high-grade localized prostate cancer, a strong family history of prostate cancer, or a known family history of BRCA1/2 mutations/Lynch syndrome/hereditary breast and ovarian cancer.
Grading and staging
Grading, based on the resemblance of tumor architecture to normal glandular structure, helps define the aggressiveness of the tumor. Grading takes into account histologic heterogeneity in the tumor. The Gleason score is commonly used. The most prevalent pattern and the next most prevalent pattern are each assigned a grade of 1 to 5, and the two grades are added to produce a total score. Most experts consider a score ≤ 6 to be well differentiated, 7 moderately differentiated, and 8 to 10 poorly differentiated. The lower the score, the less aggressive and invasive the tumor and the better the prognosis. For localized tumors, the Gleason score helps predict the likelihood of capsular penetration, seminal vesicle invasion, and spread to lymph nodes. Gleason grades 1 and 2 have now been eliminated; as a result, the lowest score possible (3 + 3) is 6. However, a Gleason score of 6 does not sound low on a scale previously ranging from 2 to 10.
The Gleason Grade Group is a newer score to help communicate this to patients, and also to simplify pathologic grading. This new scoring system was accepted by the World Health Organization (WHO) in 2016:
Grade Group 1 = Gleason score 6 (3+3)
Grade Group 2 = Gleason score 7 (3+4)
Grade Group 3 = Gleason score 7 (4+3)
Grade Group 4 = Gleason score 8
Grade Group 5 = Gleason score 9 and 10
Gleason Grade Group, clinical stage, and PSA level together (using tables or nomograms) predict pathologic stage and prognosis better than any of them alone.
Prostate cancer is staged to define extent of the tumor (see tables and ). Transrectal ultrasonography (TRUS) or MRI of the prostate may provide information for staging, particularly about capsular penetration and seminal vesicle invasion. Patients with clinical stage T1c to T2a tumors, low Gleason score (≤ 7), and PSA < 10 ng/mL (10 mcg/L) usually get no additional staging tests before proceeding to treatment. Radionuclide bone scans are rarely helpful for finding bone metastases (they are frequently abnormal because of the trauma of arthritic changes) until the PSA is > 20 ng/mL (20 mcg/L) or unless the Gleason score is high (ie, ≥ 8 or [4 +3]). CT (or MRI) of the abdomen and pelvis is commonly done to assess pelvic and retroperitoneal lymph nodes if the Gleason score is 8 to 10 and the PSA is > 10 ng/mL (10 mcg/L), or if the PSA is > 20 ng/mL (20 mcg/L) with any Gleason score. Suspect lymph nodes can be further evaluated by using needle biopsy. An MRI may also help define the local extent of the tumor in patients with locally advanced prostate cancer (stage T3). The role of PSMA (prostate-specific membrane antigen) and fluciclovine F18 PET scanning for staging is evolving, but current guidelines (1 Diagnosis references Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more ) now suggest that PSMA-PET and that PSMA-PET/CT or PSMA-PET/MRI can be effective first-line imaging studies (instead of conventional imaging studies) for intermediate or high-risk patients.
Elevated serum acid phosphatase—especially the enzymatic assay—correlates well with the presence of metastases, particularly in lymph nodes. However, this enzyme may also be elevated in benign prostatic hyperplasia (BPH); it may also be slightly elevated after vigorous prostatic massage and in the presence of multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more , Gaucher disease Gaucher Disease Gaucher disease is a sphingolipidosis, an inherited disorder of metabolism, resulting from glucocerebrosidase deficiency, causing deposition of glucocerebroside and related compounds. Symptoms... read more , and hemolytic anemia Overview of Hemolytic Anemia At the end of their normal life span (about 120 days), red blood cells (RBCs) are removed from the circulation. Hemolysis is defined as premature destruction and hence a shortened RBC life span... read more . It is rarely used today to guide treatment or to follow patients after treatment, especially because its value when done as a radioimmune assay (the way it is usually done) has not been established. Reverse transcriptase–polymerase chain reaction assays for circulating prostate cancer cells are being studied as staging and prognostic tools.
Risk of cancer spread can be estimated by tumor stage, Gleason score (Gleason Grade Group), and PSA level:
Low risk: Stage ≤ T2a, Gleason score = 6 (Gleason Grade Group 1), and PSA level ≤ 10 ng/mL (10 mcg/L)
Intermediate risk: Stage T2b-c, Gleason score = 7 (Gleason Grade Group 2-3), or PSA level ≥ 10 (10 mcg/L) and ≤ 20 ng/mL (20 mcg/L)
High risk: Stage ≥ T3, Gleason score ≥ 8 (Gleason Grade Group 4-5), or PSA ≥ 20 ng/mL (20 mcg/L)
Both acid phosphatase and PSA levels decrease after treatment and increase with recurrence, but PSA is the most sensitive marker for monitoring cancer progression and response to treatment and has virtually replaced acid phosphatase for this purpose.
1. de Vos II, Meertens A, Hogenhout R, et al: A detailed evaluation of the effect of prostate-specific antigen-based screening on morbidity and mortality of prostate cancer: 21-year follow-up results of the Rotterdam section of the European Randomised Study of Screening for Prostate Cancer. Eur Urol 84(4):426-434, 2023. doi: 10.1016/j.eururo.2023.03.016
2. European Randomized Study of Screening for Prostate Cancer. Accessed September 10, 2023.
3. Shoag JE, Mittal S, Hu JC: Reevaluating PSA testing rates in the PLCO trial. N Engl J Med 374(18):1795-1796, 2016. doi: 10.1056/NEJMc1515131
4. U.S. Preventive Services Task Force: Prostate cancer: Screening. Final recommendation statement. Accessed September 6, 2023.
Treatment of Prostate Cancer
For localized cancer within the prostate, surgery, radiation therapy, or active surveillance
For cancer outside of the prostate, palliation with hormonal therapy, radiation therapy, or chemotherapy
For some men who have low-risk cancers, active surveillance without treatment
Treatment is guided by prostate-specific antigen (PSA) level, grade and stage of tumor, patient age, coexisting disorders, life expectancy, and patient preferences. The goal of therapy can be
Local (aimed at cure)
Systemic (aimed at decreasing or limiting tumor extent) and extending quantity and quality of life
Many patients, regardless of age, prefer definitive therapy if cancer is life-threatening and potentially curable. However, therapy is palliative rather than definitive if cancer has spread outside the prostate because cure is unlikely. Active surveillance can be used for men unlikely to benefit from definitive therapy (eg, because of older age or comorbidity); these patients are treated with palliative measures if symptoms develop.
Active surveillance is appropriate for many asymptomatic patients with low-risk, or possibly even intermediate-risk, localized prostate cancer or if life-limiting disorders coexist; in these patients, risk of death due to other causes is greater than that due to prostate cancer. This approach requires periodic digital rectal examination (DRE), PSA measurement, and monitoring of symptoms. In healthy younger men with low-risk cancer, active surveillance also requires periodic repeat biopsies. The optimal interval between biopsies has not been established, but most experts agree that it should be ≥ 1 year, possibly less frequently if biopsies have been repeatedly negative. If the cancer progresses, treatment is required. About 30% of patients undergoing active surveillance eventually require therapy. In older men, active surveillance results in the same overall survival rate as prostatectomy; however, patients who had surgery have a significantly lower risk of distant metastases and disease-specific mortality.
Local therapy is aimed at curing prostate cancer and may thus also be called definitive therapy. Radical prostatectomy, some forms of radiation therapy, and cryotherapy are the primary options. Careful counseling concerning the risks and benefits of these treatments and considerations of patient-specific characteristics (age, health, tumor characteristics) are critical in decision making.
Radical prostatectomy (removal of prostate with seminal vesicles and regional lymph nodes) is probably best for patients < 75 years old with a life expectancy of > 10 to 15 years and a tumor confined to the prostate. Prostatectomy is appropriate for some older men, based on life expectancy, coexisting disorders, and ability to tolerate surgery and anesthesia. Prostatectomy was historically done through an incision in the lower abdomen. Now, most prostatectomies are done via a robot-assisted laparoscopic approach that minimizes blood loss and hospital stay but has not been shown to alter morbidity or mortality. Complications of radical prostatectomy include urinary incontinence (which is severe in about 5 to 10%), bladder neck contracture or urethral stricture Urethral Stricture Urethral stricture is scarring that obstructs the anterior urethral lumen. Urethral stricture can be Congenital Acquired Anything that damages the urethral epithelium or corpus spongiosum can... read more (in about 7 to 20%), erectile dysfunction Erectile Dysfunction Erectile dysfunction is the inability to attain or sustain an erection satisfactory for sexual intercourse. Most erectile dysfunction is related to vascular, neurologic, psychologic, and hormonal... read more (in about 30 to 100%—heavily dependent on age and current function), and rectal injury (in 1 to 2%). Nerve-sparing radical prostatectomy reduces the likelihood of erectile dysfunction but cannot always be done, depending on tumor stage and location.
Standard external beam radiation therapy usually delivers 70 grays (Gy) in 7 weeks, but this technique has been supplanted by conformal 3-dimensional radiation therapy and by intensity-modulated radiation therapy (IMRT), which safely deliver doses approaching 80 Gy to the prostate; data indicate that the rate of local control is higher, especially for high-risk patients. Some decrease in erectile function occurs in at least 40%. Other adverse effects include radiation proctitis, cystitis, diarrhea, fatigue, and possibly urethral strictures, particularly in patients with a prior history of transurethral resection of the prostate. Results with external-beam radiation therapy, radical prostatectomy, and active monitoring were shown to be comparable at a median of 10 years after treatment for localized prostate cancer, as demonstrated in the ProtecT trial (1 Treatment references Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more ). Newer forms of external radiation therapy such as proton therapy cost more, an expense that may not be justifiable given that the benefits in men with prostate cancer have not been clearly established. External beam radiation therapy also has a role if cancer is left after radical prostatectomy or if the PSA level begins to rise after surgery and no metastasis can be found.
Recent evidence (2 Treatment references Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more ) also supports the use of radiation to the prostate in men with low-volume metastatic disease, often called oligometastatic disease, commonly defined as less than 3 to 5 metastatic sites. Recent advances in prostate cancer radiation therapy include the use of fiducial markers placed around the prostate to improve targeting. Hydrogel spacers can be placed by transrectal needle placement to help reduce rectal toxicity. The hydrogel spacers resorb with time. Hypofractionation is an evolving concept in radiation treatment, in which the total dose of radiation is divided into large doses and treatments are given once a day or less often. Hypofractionated radiation therapy is given over a shorter period of time (fewer days or weeks) than standard radiation therapy.
Brachytherapy involves the implantation of radioactive seeds into the prostate through the perineum. These seeds emit a burst of radiation over a finite period (usually 3 to 6 months) and are then inert. Research protocols are examining whether high-quality implants used as monotherapy or implants plus external beam radiation therapy are superior for intermediate-risk patients. Brachytherapy also decreases erectile function, although onset may be delayed and patients may be more responsive to phosphodiesterase type 5 inhibitors than patients whose neurovascular bundles are resected or injured during surgery. Urinary frequency, urgency, and, less often, retention are common but usually subside over time. Other adverse effects include increased bowel movements; rectal urgency, bleeding, or ulceration; and prostatorectal fistulas.
Cryotherapy (destruction of prostate cancer cells by freezing with cryoprobes, followed by thawing) is less well established; long-term outcomes are unknown. Adverse effects include bladder outlet obstruction Obstructive Uropathy Obstructive uropathy is structural or functional hindrance of normal urine flow, sometimes leading to renal dysfunction (obstructive nephropathy). Symptoms, less likely in chronic obstruction... read more , urinary incontinence Urinary Incontinence in Adults Urinary incontinence is involuntary loss of urine; some experts consider it present only when a patient thinks it is a problem. The disorder is greatly underrecognized and underreported. Many... read more , erectile dysfunction Erectile Dysfunction Erectile dysfunction is the inability to attain or sustain an erection satisfactory for sexual intercourse. Most erectile dysfunction is related to vascular, neurologic, psychologic, and hormonal... read more , and rectal pain or injury. Cryotherapy is not commonly the therapy of choice in the United States but may be used if radiation therapy is unsuccessful.
HIFU (high-intensity focused ultrasound) uses intense ultrasound energy administered transrectally to ablate prostate tissue. It has been used for many years in Europe and Canada and has recently become more widely available in the United States. The role of this technology in the management of prostate cancer is evolving; presently, it appears to be best suited for radiation-recurrent prostate cancer or low-risk cancer with individual tumors that can be treated by focal therapy. Several other investigational therapies to treat focal lesions are under study, such as laser ablation and catheter electroporation.
If cancer localized to the prostate is high risk, various therapies may need to be combined (eg, for high-risk prostate cancer treated with external beam radiation, addition of hormonal therapy for periods varying from 6 months to 2 to 3 years).
If cancer has spread beyond the prostate gland, cure is unlikely; systemic treatment aimed at decreasing or limiting tumor extent is usually given (3 Treatment references Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more ).
Patients with a locally advanced tumor or metastases may benefit from androgen deprivation therapy (ADT) by castration, either surgically with bilateral orchiectomy or medically with luteinizing hormone–releasing hormone (LHRH) agonists, such as leuprolide, goserelin, triptorelin, histrelin, and buserelin, with or without radiation therapy. LHRH antagonists (eg, parenteral degarelix, oral relugolix) lower the testosterone level more rapidly than LHRH agonists. LHRH agonists and LHRH antagonists usually reduce serum testosterone almost as much as bilateral orchiectomy. Androgen-receptor targeted therapies (abiraterone acetate with prednisone, enzalutamide, apalutamide, darolutamide) or chemotherapy (docetaxel) can be given in combination with ADT; choice of therapy is determined by volume of metastatic disease and patient comorbidities.
All androgen-deprivation treatments cause loss of libido and erectile dysfunction Erectile Dysfunction Erectile dysfunction is the inability to attain or sustain an erection satisfactory for sexual intercourse. Most erectile dysfunction is related to vascular, neurologic, psychologic, and hormonal... read more and may cause hot flushes Vasomotor Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more . LHRH agonists may cause PSA levels to increase temporarily. Some patients benefit from adding antiandrogens (eg, flutamide, bicalutamide, nilutamide, cyproterone acetate [not available in the United States]) for total androgen blockade. Combined androgen blockade usually refers to LHRH agonists plus antiandrogens, but its benefits appear minimally better than those of an LHRH agonist (or LHRH antagonist or orchiectomy) alone. Another approach is intermittent androgen blockade, which purports to delay emergence of androgen-independent prostate cancer and helps to limit some adverse effects of androgen deprivation. Total androgen ablation is given until PSA levels are reduced (usually to undetectable levels), then stopped. Treatment is started again when PSA levels rise above a certain threshold, although the ideal threshold is not yet defined. The optimal schedules for treatment and time-off treatment have not been determined and vary widely among practitioners.
Androgen deprivation may impair quality of life significantly (eg, self-image, attitude toward the cancer and its treatment, energy levels) and cause osteoporosis, anemia, and loss of muscle mass with long-term treatment. Exogenous estrogens are rarely used because they have a risk of cardiovascular and thromboembolic complications.
Hormonal therapy is effective in metastatic prostate cancer for a limited amount of time. Cancer that progresses (indicated by an increasing PSA level) despite a testosterone level consistent with castration (< 50 ng/dL [1.74 nmol/L]) is classified as castrate-resistant prostate cancer. Castrate-resistant prostate cancer (CRPC) can be further classified as M0 (nonmetastatic) CRPC or M1 (metastatic) prostate cancer. An increasing PSA despite low testosterone and absence of lesions on CT or bone scan is called nonmetastatic castrate-resistant prostate cancer. Risk of metastases is high. Apalutamide, darolutamide, and enzalutamide are now available and can slow progression from M0 to M1 CRPC. Treatments that prolong survival in metastatic CRPC (most have been FDA approved since 2010) that should be combined with testosterone suppression include
Docetaxel (a taxane chemotherapy drug)
Sipuleucel-T (a patient-derived vaccine designed to induce immunity against prostate cancer cells)
Abiraterone (which blocks androgen synthesis in the tumor as well as in the testes and adrenal glands)
Enzalutamide, darolutamide, apalutamide (which block binding of androgens to their receptors)
Cabazitaxel (a taxane chemotherapy drug that may have activity in tumors that have become resistant to docetaxel)
Radium-233 (which emits alpha radiation, recently found to prolong survival as well as prevent complications due to bone metastases in men with CRPC)
External beam radiation therapy (EBRT)
PARP (poly [ADP-ribose]) inhibitors (olaparib, rucaparib), which appear active when used as monotherapy in patients with mCRPC and BRCA1/2 and other mutations. The PARP inhibitor talazoparib is available in combination with enzalutamide, and olaparib is now also used in combination with abiraterone/prednisone as well with BRCA-mutated metastatic castration-resistant prostate cancer.
Lutetium Lu 177 vipivotide tetraxetan, which specifically targets a molecule on the surface of prostate cancer cells and is given with a PSMA-positive PET/CT scan.
Some data suggest that sipuleucel-T should be used at the earliest sign of CRPC with low PSA and no major symptoms of metastatic cancer (eg, pain). In general, treatments for CRPC are being tried earlier during the course of prostate cancer and are now showing benefit in hormone-sensitive metastatic prostate cancer. However, choice of treatment may involve many factors, and few data may be available to help predict results; thus familiarity with current clinical trials, patient education, and shared decision-making are recommended.
To help treat and prevent complications due to bone metastases (eg, pathologic fractures, pain, spinal cord compression), an osteoclast inhibitor (eg, denosumab, zoledronic acid) can be used. All men on ADT should be given vitamin D and calcium supplements with the selective use of DEXA scans to detect osteoporosis or osteopenia. Weight-bearing exercise may also help maintain weight, bone density, muscle mass, and core strength. Traditional external beam radiation therapy has been used to treat individual bone metastases.
1. Hamdy FC, Donovan JL, Lane JA, et al: 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl Med 375(15):1415-1424, 2016. doi: 10.1056/NEJMoa1606220
2. Parker CC, James ND, Brawley CD, et al: Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): A randomised controlled phase 3 trial. Lancet 392(10162):2353-2366, 2018. doi: 10.1016/S0140-6736(18)32486-3
3. Posdzich P, Darr C, Hilser T, et al: Metastatic prostate cancer—A review of current treatment options and promising new approaches. Cancers 15(2):461, 2023. https://doi.org/10.3390/cancers15020461
Prognosis for Prostate Cancer
Prognosis for most patients with prostate cancer, especially when it is localized or regional, is very good. Life expectancy for older men with prostate cancer may differ little from age-matched men without prostate cancer, depending on their age and comorbidities. For many patients, long-term local control, or even cure, is possible. Potential for cure, even when cancer is clinically localized, depends on the tumor’s grade and stage. Without early treatment, patients with high-grade, poorly differentiated cancer have a poor prognosis. Undifferentiated prostate cancer, squamous cell carcinoma, and ductal transitional carcinoma respond poorly to conventional therapies. Metastatic cancer has no cure but may be sent into remission for many years using newer therapies. Median life expectancy with metastatic disease is typically 1 to 3 years, with some patients living for many years.
Prevention of Prostate Cancer
No measures reliably prevent prostate cancer. However, suggestions that following a healthy lifestyle—which includes exercising, eating a well-balanced diet (limiting red meat and saturated fats and eating abundant green leafy vegetables), limiting alcohol intake, and not smoking—is considered a reasonable approach.
Prostate cancer develops very commonly with aging but is not always clinically important.
Symptoms develop only after the cancer has enlarged enough to be more difficult to cure.
Complications due to bone metastases are common and consequential.
Diagnose prostate cancer by transrectal or transperineal ultrasound-guided needle biopsy.
Discuss advantages and disadvantages of screening in men > age 50 with life expectancy > 10 or 15 years.
For localized prostate cancer, consider local, curative treatment (eg, prostatectomy, radiation therapy) and active surveillance.
For cancer that has spread beyond the prostate, consider systemic treatments (eg, various hormonal therapies, sipuleucel-T, taxane chemotherapy).
For bone metastases, consider radium-233 and osteoclast inhibitors.
Drugs Mentioned In This Article
|Drug Name||Select Trade|
|Androderm, AndroGel, Andro-L.A., Aveed, AXIRON, Delatestryl, Depo-Testosterone, FORTESTA, JATENZO, KYZATREX, Natesto, STRIANT, Testim, Testoderm, Testopel, TLANDO, Virilon, Vogelxo, XYOSTED|
|CAMCEVI, Eligard, Fensolvi, Lupron, Lupron Depot, Lupron Depot-Ped, Viadur|
|Zoladex, Zoladex 3-Month|
|Trelstar, Trelstar Depot, Trelstar Depot Plus Debioclip, Trelstar LA, Trelstar LA Plus Debioclip, Triptodur|
|Supprelin, Supprelin LA, Vantas|
|Deltasone, Predone, RAYOS, Sterapred, Sterapred DS|
|Docefrez , Taxotere|
|Reclast, Zometa, Zometa Powder|
|Calcidol, Calciferol, D3 Vitamin, DECARA, Deltalin, Dialyvite Vitamin D, Dialyvite Vitamin D3, Drisdol, D-Vita, Enfamil D-Vi-Sol, Ergo D, Fiber with Vitamin D3 Gummies Gluten-Free, Happy Sunshine Vitamin D3, MAXIMUM D3, PureMark Naturals Vitamin D, Replesta, Replesta Children's, Super Happy SUNSHINE Vitamin D3, Thera-D 2000, Thera-D 4000, Thera-D Rapid Repletion, THERA-D SPORT, UpSpring Baby Vitamin D, UpSpring Baby Vitamin D3, YumVs, YumVs Kids ZERO, YumVs ZERO|