What Is Advanced Prostate Cancer and How Is It Treated?
More than 240,000 Americans are diagnosed with prostate cancer every year, making it the second most common cancer affecting men behind skin cancer. Most are diagnosed at 65 or older, and among them, about 86% have early-stage disease with zero spread. That leaves 13% with more advanced prostate cancer, meaning the cancer has metastasized into nearby tissue, lymph nodes, or other parts of the body. Or, that it’s recurrent, meaning it’s come back after treatment. Let’s take a look at the different ways advanced prostate cancer can present itself, then dig into the most effective ways it can be treated.
Type 1: Biochemical Recurrence (BCR)
Prostate-specific antigen (PSA) levels are markers for prostate cancer. With biochemical recurrence (BCR), “prostate cancer has come back in the form of a PSA rise by itself, but the cancer is not visible on any imaging,” explains oncologist Rana R. McKay, M.D., associate professor of medicine at UC San Diego. “Some don’t consider BCR an advanced disease because men with it technically don't have any masses. However, others do, since the disease cannot be cured.” While some men eventually develop disease spread after BCR, a decent amount don’t, according to a 2019 report in the journal European Urology.
Type 2: Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
With mHSPC, the cancer has spread from the primary site (the prostate) to the bones, lymph nodes outside the pelvis, or other organs. “Hormone sensitive” means that your prostate cancer can be treated with a hormone therapy called androgen deprivation therapy (ADT). So, mHSPC is a cancer that has spread beyond the prostate that has yet to be treated with hormone therapy. “ADT blocks the specific male hormones called androgen, which includes testosterone, mostly coming from the testes,” says Gurkamal Chatta, M.D., clinical chief of genitourinary medicine at Roswell Park Comprehensive Cancer Center in Buffalo, NY.
Type 3: Metastatic Castration-Resistant Prostate Cancer (mCRPC)
“Metastatic” means that the cancer has spread, but with mCRPC, cancer continues to grow and advance even with very low levels of testosterone in the body—a.k.a, it’s “castration resistant.” That means that “blocking testosterone from testes with ADT is not enough to push the disease back,” explains Dr. Chatta. (Metastatic castration-resistant prostate cancer used to be called hormone-resistant or refractory prostate cancer, but that has fallen out of favor since certain hormone therapies can, in fact, treat mCRPC.) Most cases of mCRPC occur after completing your first treatment—or even years later.
Type 4: Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC)
When mCRPC recurs despite hormone treatment and doesn’t show up on imaging, it’s called non-metastatic castration-resistant prostate cancer (nmCRPC). Essentially, nmCRPC is a “man-made” castration-resistant prostate cancer that occurs post-treatment. “With today’s advanced imaging, however, nmCRPC is an ever-dwindling diagnosis,” says Dr. McKay. Translation: Many prostate cancers that would have been diagnosed as nmCRPC are now being diagnosed as mCRPC because the “m” (malignancy or masses) can now be detected on better-quality scans.
Treatment Goals for All Types of Advanced Cancer
“Today, our goal in treating men with advanced prostate cancer is to control, not cure,” says Dr. Chatta. That means physicians and patients alike focus on treatments that’ll help to shrink the tumor and control symptoms. Even though a cure is not yet in the cards for advanced prostate cancer, “someone with an advanced diagnosis can still be expected to have favorable survival rates,” says Dr. Chatta. So even with recurrence, it’s possible to add years (and sometimes many years) to a patient’s life with the right treatment approach, he adds.
Hormone Therapy for Advanced or Recurring Prostate Cancer
“Mostly everyone with advanced or recurrent prostate cancer is treated with some form of hormone therapy,” says Dr. McKay. “It’s the backbone of systemic therapy.” According to the American Cancer Society, hormone therapy is used when cancer has spread too far to be eradicated by surgery or radiation; cancer remains (or returns) after surgery or radiation therapy; you have a higher risk of the cancer returning after treatment; or, you’re also getting radiation. (Hormone therapy helps to shrink the tumor, making radiation more effective.)
According to the American Urological Association, men with biochemical recurrence should be considered for observation or enrollment in a clinical trial after their PSA levels, general health, and previous treatments have been reviewed. While androgen deprivation therapy (ADT) is not always recommended, “BCR is typically thought of as hormone-sensitive, so hormone treatment can sometimes be used,” notes Dr. McKay. Radiation therapy is an option for some men who developed BCR after surgery. For those who’ve already received radiation, surgery to partially (or completely) remove the prostate may be an option.
Treating Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
As noted earlier, metastatic hormone-sensitive prostate cancer is treated with androgen deprivation therapy (ADT), which is any treatment that lowers a man’s androgen (sex hormone) levels. (This is also called hormone therapy.) Such treatments may include a surgical procedure known as orchiectomy to remove the testicles (instead of using ADT meds), or primary ADT therapy, which uses either LHRH agonists (medications that lower testosterone made by the testicles) or Gn-RH antagonists (drugs that block the pituitary gland from making testosterone).
More on Managing mHSPC
“Hormonal therapy is the cornerstone of mHSPC treatment, but now we know that adding and intensifying that therapy with pills or chemo for some improves outcomes,” says Dr. McKay. Other options to be combined with ADT include radiotherapy to help control prostate cancer in the prostate gland itself; chemotherapy with the drug docetaxel (Docefrez) which has been shown to help men live longer, as well reduce pain; and androgen pathway-directed therapy, which uses medications that are relatively new second-generation anti-androgens agents, per the latest National Comprehensive Cancer Network's guidelines.
Treating Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC)
Until 2018, there were no official FDA-approved treatments for nmCRPC. Luckily, things have changed and now there are a range of medication options for men with nmCRPC who are at an elevated risk of metastases using second-generation anti-androgens. New research notes that second-gen meds have “revolutionized the treatment landscape for nmCRPC.” Currently, certain men with nmCRPC should be treated with these drugs, in addition to continuing ADT, in order to delay disease spread. “We are definitely seeing this strategy improve outcomes,” says Dr. McKay.
Treating Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Some common treatments for mCRPC include chemotherapies and new second-gen anti-androgens. A 2019 report in the journal Lancet Oncology noted that starting with the drug Zytiga (abiraterone) and followed by Xtandi (enzalutamide) is likely the best course of action with anti-androgens. Adding to the arsenal are new FDA-approved targeted therapies, which are called PARP inhibitors, used to treat cancers with specific mutations. While not for everyone, Dr. Chatta notes that “we’ve seen response rates at 50% to 60% with these drugs, which can prolong survival by six months to a year. They are real game-changers.”
A “Vaccine” for mCRPC
“Sipuleucel-T (Provenge) is the first FDA-approved cancer vaccine to treat solid tumors, and it’s shown to improve survival for those with advanced disease,” says Dr. McKay. Sipuleucel-T stimulates the immune system to recognize and destroy prostate cancer cells more effectively. Called immunotherapy, it’s made from a mix of your own white blood cells and a specific protein from prostate cancer cells. According to the American Cancer Society it’s used when advanced prostate cancer is no longer responding to hormone therapy but causes few or no symptoms. While it might not lower PSA levels, it may help men live longer.
When Advanced Prostate Cancer Has Spread to the Bones
“While prostate cancer can spread to any part of the body, the most common site is the bones,” says Dr. Chatta. A class of drugs called bisphosphonates or denosumab can often help to reduce pain and slow cancer growth. External radiation therapy may also be used, but only if bone pain is limited to a few spots. Other options include corticosteroids, which may help relieve bone pain and lower PSA levels. Radiopharmaceuticals use radioactive elements that are injected into a vein and then settle into damaged bones, giving off radiation to kill cancer cells (used when pain is widespread).
Treatments Keep Improving
“It’s an incredibly exciting time for advanced prostate cancer research,” says Dr. McKay. “There are a lot of new drugs on the horizon, and drugs with very novel mechanisms of action. I feel like we just opened Pandora's Box of additional targeted therapies and strategies for this disease.” Indeed, there are 900+ companies currently developing prostate cancer therapies, with nine expected to be available in the next decade. One of those is a Phase III targeted therapy for mCRPC, which binds to specific prostate cancer cells, where a radioactive isotope damages the cells, triggering cancer cell death. Watch this space.
- Prostate Cancer Numbers (1): American Cancer Society. (2021.) “Key Statistics for Prostate Cancer.” cancer.org/cancer/prostate-cancer/about/key-statistics.html
- Prostate Cancer Numbers (2): CA: A Cancer Journal for Clinicians. (2020.) “Rates of advanced prostate cancer continue to increase.” acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21641
- BCR Outcomes: European Urology. (2019.) “Prognostic Value of Biochemical Recurrence Following Treatment with Curative Intent for Prostate Cancer: A Systematic Review.” sciencedirect.com/science/article/abs/pii/S0302283818307528?via%3Dihub
- Hormone Resistant Prostate Cancer: International Journal of Molecular Science. (2018.) “Profiling Prostate Cancer Therapeutic Resistance.” mdpi.com/1422-0067/19/3/904
- News on nmCRPC: Clinical Medicine Insights: Oncology. (2019.) “The Current Landscape of Treatment in Non-Metastatic Castration-Resistant Prostate Cancer.” ncbi.nlm.nih.gov/pmc/articles/PMC6407161/
- Number of nmCRPC Cases: Cancer Management and Research. (2019.) “Treatment of non-metastatic castration-resistant prostate cancer: focus on apalutamide.” ncbi.nlm.nih.gov/pmc/articles/PMC6682169/
- Hormone Therapy Options for Advanced Prostate Cancer: American Cancer Society. (2020.) “Hormone Therapy for Prostate Cancer.” cancer.org/cancer/prostate-cancer/treating/hormone-therapy.html
- Treatment Overview for Advanced Prostate Cancer: Cancer.Net. (2020.) “Prostate Cancer: Types of Treatment.” cancer.net/cancer-types/prostate-cancer/types-treatment
- Updates in Advanced Prostate Cancer Care: Cancer Network. (2020.) “Experts Develop New Guideline for Advanced Prostate Cancer.” cancernetwork.com/view/experts-develop-new-guideline-for-advanced-prostate-cancer
- First Oral Hormone Therapy for Advanced Prostate Cancer: Food and Drug Administration. (2020.) “FDA Approves First Oral Hormone Therapy for Treating Advanced Prostate Cancer.” fda.gov/news-events/press-announcements/fda-approves-first-oral-hormone-therapy-treating-advanced-prostate-cancer
- New Advanced Prostate Cancer Treatments: Food and Drug Administration. (2020.) “FDA approves relugolix for advanced prostate cancer.” fda.gov/drugs/drug-approvals-and-databases/fda-approves-relugolix-advanced-prostate-cancer
- Recurrent Disease Treatment: American Cancer Society. (2020.) “Treating Prostate Cancer That Doesn’t Go Away or Comes Back After Treatment.” cancer.org/cancer/prostate-cancer/treating/recurrence.html
- Androgen Pathway-Directed Therapy Recommendations: Journal of the National Comprehensive Cancer Network. (2019.) “Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.” jnccn.org/view/journals/jnccn/17/5/article-p479.xml
- Info on Second-Gen Medications (1): Prostate Cancer and Prostatic Diseases. (2021.) “Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors.” nature.com/articles/s41391-020-00310-3
- Info on Second-Gen Medications (2): The Lancet Oncology. (2019.) “Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial.” sciencedirect.com/science/article/abs/pii/S1470204519306886?via%3Dihub
- PARP Inhibitors: Genes, Chromosomes & Cancer. (2020.) “PARP inhibition in prostate cancer.” onlinelibrary.wiley.com/doi/full/10.1002/gcc.22903
- Immunotherapy for Advanced Prostate Cancer: American Cancer Society. (2019.) “Immunotherapy for Prostate Cancer.” cancer.org/cancer/prostate-cancer/treating/vaccine-treatment.html
- Advanced Prostate Cancer and Bone Spread: American Cancer Society. (2019.) “Treatments for Prostate Cancer Spread to Bones.” cancer.org/cancer/prostate-cancer/treating/treating-pain.html
- Future of Advanced Prostate Cancer Treatment: DelveInsight. (2021.) “Prostate cancer - Pipeline Insights, 2021.” delveinsight.com/report-store/prostate-cancer-pipeline-insight
- Innovations in Advanced Prostate Cancer Treatment: Novartis. (2021.) “Novartis announces positive result of phase III study with radioligand therapy 177Lu-PSMA-617 in patients with advanced prostate cancer.” novartis.com/news/media-releases/novartis-announces-positive-result-phase-iii-study-radioligand-therapy-177lu-psma-617-patients-advanced-prostate-cancer