Advanced Prostate Cancer

Patient Guideline Summary

Publication Date: April 25, 2023
Last Updated: May 1, 2023

Objective

Objective

This patient summary discusses key recommendations from the American Urological Association (AUA), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO) for advanced prostate cancer. It is limited to adults 18 years of age and older and should not be used as a reference for children.

Overview

Overview

  • Prostate cancer is the most common male solid organ malignancy in the U.S. It is also the second leading cause of cancer deaths in men. It usually begins dependent on male hormones but often becomes resistant to androgen-deprivation treatment (ADT) if it recurs. Prostate cancer that no longer depends on male hormones is called castration-resistant prostate cancer (CRPC).
  • Prostate cancer starts in the prostate. If not detected and treated early by an annual check-up and positive screening test for prostate-specific antigen (PSA), it will spread locally and to other organs.
  • After early local therapy with surgery, radiation or ADT, it may:
    • Be cured.
    • Recur, the first sign being a rising PSA without visible metastases (cancer spread to another place). Rising PSA after local treatment is called “biochemical recurrence.”
    • Recur as metastatic hormone-sensitive prostate cancer (mHSPC).
    • Progress to CRPC whether metastatic (mCRPC) or not metastatic (nmCRPC).
  • Prostate cancer deaths are typically the result of progression to mCRPC. But, due to novel therapies, survival is now increasing.
  • This patient summary covers advanced prostate cancer, including recurrence after exhaustion (using up) of local treatment options and widespread metastatic disease.

Early Evaluation and Counseling

Early Evaluation and Counseling

  • If you have clinical signs and symptoms suggestive of advanced prostate cancer, your doctor will plan for a biopsy to confirm the diagnosis. Although the clinical picture is often consistent with the diagnosis, treatment may strongly depend on the unique nature of your cancer.
  • Your doctor will discuss treatment options based on life expectancy, comorbidities (other important medical conditions), your preferences, and your tumor characteristics. Your care may include a team specialized in urology, medical oncology (the diagnosis and treatment of cancer), endocrinology (hormone-related), palliative medicine, and radiation oncology.
  • Your doctor will manage your pain and other symptoms and may suggest patient advocacy groups.

Biochemical Recurrence Without Metastatic Disease After Exhaustion of Local Treatment Options

Biochemical Recurrence Without Metastatic Disease After Exhaustion of Local Treatment Options

  1. Prognosis
  • If you have PSA recurrence after exhaustion of local therapy, your doctor will inform you regarding the risk of developing metastatic disease and will follow up with serial PSA measurements and clinical evaluation. He may also consider x-ray (imaging) assessments.
  • If you have PSA recurrence after exhaustion of local therapy AND are at higher risk for the development of metastases, your doctor may perform periodic imaging including CT, Magnetic Resonance Imaging (MRI), and technetium bone scanning or PSMA PET imaging (a new imaging technique).
    • PSMA PET imaging is preferred if available.
  • If you have PSA recurrence after the failure of local therapy, your doctor may use novel PET-CT (Positron Emission Tomography and Computed Tomography) scans as an alternative to conventional imaging or in case of negative conventional imaging.
  1. Treatment
  • If you have a rising PSA after the failure of local therapy and no metastatic disease by conventional imaging, your doctor will offer an observation or clinical trial enrollment.
    • In clinical trials, new drugs and other kinds of treatments (like radiation and chemotherapy) are constantly being tested for effect and safety by carefully controlled experiments in patients with diseases like cancer. In many cases, these are recommended to patients when they are available. Your doctor will advise you if a clinical trial is a reasonable choice for you.
  • Although not recommended, if androgen deprivation therapy (ADT) is started in the absence of visible metastases for men who have completed maximal local therapy, intermittent ADT may be offered instead of continuous ADT.

Metastatic Hormone-Sensitive Prostate Cancer

Metastatic Hormone-Sensitive Prostate Cancer

  1. Prognosis
  • If you are a newly diagnosed mHSPC patient, your doctor will assess:
    • The extent of metastatic disease (bone, lymph node, and visceral metastasis) using conventional imaging.
      • High-volume extent is defined as four or more bone metastases with at least one metastasis outside of the spine and pelvis and/or the presence of visceral metastases.
      • If you do not qualify for “High-volume,” then you are “Low-volume.”
    • Your symptoms, such as bone pain from metastatic disease, because this affects both the prognosis and management.
  • If you are an mHSPC patient, your doctor will assess baseline PSA and serial PSAs at three-to six-month intervals after initiation of ADT and may consider periodic conventional imaging.
  • If you have mHSPC, regardless of your age and family history, your doctor may offer genetic counseling and germline testing.
  1. Treatment
  • Your doctor may offer ADT in combination with either androgen pathway directed therapy (abiraterone acetate plus prednisone, apalutamide, enzalutamide) or chemotherapy (docetaxel).
  • If you are an mHSPC patient with low-volume metastatic disease, your doctor may offer primary radiotherapy to the prostate in combination with ADT.
  • In selected patients with de novo mHSPC, ADT in combination with docetaxel and either abiraterone acetate plus prednisone or darolutamide maybe offered.

Non-Metastatic Castration-Resistant Prostate Cancer

Non-Metastatic Castration-Resistant Prostate Cancer

  1. Prognosis
  • Your doctor should obtain serial PSA measurements at three- to six-month intervals and calculate a PSA doubling time (PSADT) starting at the time of development of castration-resistance.
    • PSADT is the number of months required for the PSA to double.
    • The higher the number, the better the prognosis.
  • Your doctor should also obtain conventional or PSMA PET imaging at intervals of 6 to 12 months
  1. Treatment
  • Your doctor will probably offer one of these drugs — apalutamide, darolutamide, or enzalutamide— with continued ADT if you are at high risk for developing metastatic disease.
  • Your doctor may recommend observation with continued ADT, particularly if you are at lower risk for developing metastatic disease.
  • It is recommended to have systemic chemotherapy or immunotherapy only within a clinical trial.

Metastatic Castration-Resistant Prostate Cancer

Metastatic Castration-Resistant Prostate Cancer

  1. Prognosis
  • Your doctor will probably obtain baseline blood tests (e.g., PSA, testosterone, LDH, Hgb, alkaline phosphatase level) and review the location of metastatic disease (bone, lymph node, viscera), your symptoms and performance status (a system to quantify the overall decrease in your ability to live your life) to help discussions of decision making.
  • Your doctor may assess the extent of metastatic disease using conventional imaging at least once per year or more frequently if you are not responding to treatment.
  • Your doctor may offer genetic testing to identify DNA mutations (changes) that may inform prognosis and counseling regarding family risk as well as potential targeted therapies.
  1. Treatment
  • If you are newly diagnosed with mCRPC, your doctor may offer continued ADT with abiraterone acetate plus prednisone, docetaxel, or enzalutamide. These are chemotherapy agents with an FDA indication for use in men with mCRPC.
  • If you are an mCRPC patient with no or minimal symptoms, your doctor may offer sipuleucel-T, which is immunotherapy (treatment that uses a person's immune system to fight diseases such as cancer).
  • Your doctor will probably offer radium-223 if you have symptoms from bony metastases and are without known visceral disease or lymphadenopathy (swollen lymph nodes) larger than 3cm. Radium-223 induces DNA breaks in cancer cells while minimizing damage to surrounding marrow.
  • Increasing knowledge of cancer genetics and multiple treatment plans and agents with various levels of clinical experience continue to improve care and understanding of prostate cancer. Progress continues. Your treatment team may have even more current information to guide your treatment.

Bone health of patients with advanced prostate cancer

Bone health of patients with advanced prostate cancer

  • Several factors place the average patient with metastatic prostate cancer at a higher risk of bone complications:
    • The age of onset of the disease already coincides with the physiologic, age-related decreases in bone mineral density.
    • A primary therapy in patients with recurrent disease (i.e., ADT) is associated with progressive loss of bone mineral density, increasing your fracture risk.
    • In patients with advanced disease, bones are the most common site of metastatic disease.
  • Your doctor will discuss the risk of osteoporosis associated with ADT and may assess the risk of fragility fracture.
  • If you are on ADT, your doctor will probably recommend preventive treatment for fractures, including supplemental calcium, vitamin D, smoking cessation, and weight-bearing exercise.
  • If you are at high fracture risk due to bone loss, your doctor may recommend preventive treatments with bisphosphonates or denosumab and referral to physicians who have familiarity with the management of osteoporosis. These may include endocrinologists, orthopedic surgeons, or primary care physicians.
  • The uncommon but serious toxicity of bisphosphonates or denosumab is osteonecrosis of the jaw (ONJ). Men who need dental extractions while on these agents are at higher risk for ONJ. So, make sure to be evaluated by a dentist before the start of the treatment.
  • Your doctor may prescribe a bone-protective agent (denosumab or zoledronic acid) if you are an mCRPC patient with bony metastases.

Abbreviations

  • ADT: Androgen Deprivation Therapy
  • ASTRO: American Society For Radiation Oncology
  • AUA: American Urologic Association
  • CRPC: Castration-resistant Prostate Cancer
  • MRI: Magnetic Resonance Imaging
  • ONJ: Osteonecrosis Of The Jaw
  • PET-CT: Positron Emission Tomography And Computed Tomography
  • PSA: Prostate-specific Antigen
  • PSADT: PSA Doubling Time
  • SUO: Society Of Urologic Oncology
  • mCRPC: Metastatic Castration-resistant Prostate Cancer
  • nmCRPC: Non-metastatic Castration-resistant Prostate Cancer

Source Citation

Lowrance W, Dreicer R, Jarrard DF, Scarpato KR, Kim SK, Kirkby E, Buckley DI, Griffin JC, Cookson MS. Updates to Advanced Prostate Cancer: AUA/SUO Guideline (2023). J Urol. 2023 Apr 25:101097JU0000000000003452. doi: 10.1097/JU.0000000000003452. Epub ahead of print. PMID: 37096583.

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.