Castration Sensitive & Resistant: Understanding Prostate Cancer Terms
- Prostate cancer can be classified into categories based on how well it responds to hormone therapy: castrate sensitive (hormone sensitive) and castrate resistant (hormone resistance).
- “Initially most people will be very sensitive to the hormone therapy and will respond well, but at some point they do stop responding to it, at which point we call them castrate resistant or androgen resistant,” Dr. Akshay Bhandari, director of robotic surgery at Mount Sinai Medical Center in Miami, explains.
- It’s important to understand that even when prostate cancer becomes resistant to hormone therapy, there are many treatment options available — from next-generation hormone blockers to targeted radioligand therapy and beyond.
“Advanced” prostate cancer can mean many different things, and it’s sometimes difficult for patients to understand the terms their doctors are throwing out.
Read MoreA Quick Refresher: Why Hormones Matter
Testosterone is fuel for most prostate-cancer cells. Take that fuel away and tumors — especially early ones — often shrink or stall. Doctors call that approach androgen-deprivation therapy (ADT).“Androgen deprivation is usually the first line therapy. Even when people move on to more advanced therapies, they usually are on androgen deprivation therapy,” Dr. Bhandari explains.
It can be an injection every few months or a daily pill. The medical lingo for a tumor that still responds to this strategy is hormone-sensitive (or “castration-sensitive”) disease.
As Dr. Bhandari explains, sooner or later, some cancer cells learn a work-around.
“They start bypassing those typical pathways,” he says.
That stage is hormone-resistant (also called castration-resistant). It’s the same disease, but it requires a different treatment approach.
Hormone-Sensitive Metastatic Prostate Cancer
Typically, a blood test, usually one that indicates a spike in PSA (prostate-specific antigen — a protein made by the prostate) is the first sign of prostate cancer. Then a bone scan or, more likely these days, a PSMA PET scan, lights up a tiny spot in a rib or a pelvic lymph node. If it’s outside the prostate, the cancer is often labeled metastatic — but it can still be hormone-sensitive.
Dr. Bhandari’s team often begins with ADT. The goal is simple: starve the cancer. Chemical castration sounds harsh, yet plenty of men tolerate it far better than they feared.
Common side effects include:
- Hot flashes
- Night sweats
- Fatigue or “brain fog”
- Weight gain around the middle
- A dip in sex drive
Fortunately, most of these side effects are temporary and/or can be managed.
Adding things like calcium, vitamin D, and physical activity into your routine can help, too.
When Hormone Therapy Stops Working
Some men cruise for years on ADT alone, yet tumors can, and do, adapt. You’ll hear physicians toss around the term PSA doubling time. If a man’s PSA, while on treatment, doubles in less than six months, we start thinking about resistance. If it stays low or rises only a little each year, hormones are still in the driver’s seat.
“Now these two categories [castrate sensitive and castrate resistant] can also further be divided into metastatic and non-metastatic. So you could have castrate sensitive non-metastatic prostate cancer, castrate sensitive metastatic prostate cancer and the same two classifications for the androgen or the castrate resistant classification,” Dr. Bhandari explains.
- Non-metastatic castration-resistant prostate cancer has not spread to other parts of the body (based on scans)
- Metastatic castration-resistant prostate cancer has spread to other parts of the body (such as lymph nodes or to the bones)
Castration-resistant prostate cancer (CRPC) is a type of cancer that keeps getting bigger even when the amount of testosterone in the body is very low or gone. It can also be called hormone-refractory or hormone-resistant prostate cancer. For it to be considered a castration-resistant prostate cancer, a patient’s testosterone levels are usually low (<50 ng/dL).
Your doctor can tell if you have castration-resistant prostate cancer when a blood test indicates that your prostate-specific antigen (PSA) level is going up and your testosterone level is low. Pictures from tests might also reveal that the cancer is getting bigger. Doctors might check how fast the PSA level is doubling, which is the time it takes for the PSA level to become twice as much, to help choose the right treatment.
At this point, treatment options include:
- Next-Generation Hormone Blockers: Medications like abiraterone or enzalutamide shut off testosterone signaling deeper inside the cell. They’re pills, taken at home. Many men feel perfectly normal except for a bit more fatigue on long days.
- Targeted Radioligand Therapy: Picture a microscopic delivery truck. It carries a radioactive payload, follows a “postal code” called PSMA, and drops the package right on the cancer cell. Pluvicto (Lutetium Lu 177 vipivotide tetraxetan) is the name you’ll hear most. Pluvicto is part of a newer class of targeted cancer therapies called radioligand therapies (RLTs). It delivers a small but powerful dose of radiation directly to prostate cancer cells that express a protein known as PSMA (prostate-specific membrane antigen). This protein is found on most prostate cancer cells but not on normal tissues — making it a valuable target for treatment.
- Chemotherapy: Docetaxel or cabazitaxel knock back fast-growing tumors and can relieve bone pain. The key is timing: using chemo when it brings the most benefit and least misery.
- Immunotherapy: If genetic testing shows a high mutation burden, a checkpoint inhibitor like pembrolizumab may spark the immune system. It’s a niche group, but the responses can be dramatic.
Making Treatment Choices
No algorithm can replace lived experience.
“Standard of care is important,” Dr. Bhandari explains, “but it may not be the best care for that particular patient.”
A man of seventy-nine, already battling mild dementia, may hate the fog of long-term hormones. In that case, six months on therapy, then a break, might beat the standard two-year plan.
The secret sauce is shared decision-making. Bring your worries, your bucket-list items, your spouse if you can to your appointments to actively participate in treatment decision making. Let your oncologist know what matters most — such as longevity, clarity of mind, being able to toss a baseball with the grand-kids. Treatment should honor those priorities.
What To Know About Side Effects
Side effects from prostate cancer treatment can seem daunting, scary, and uncomfortable — but rest assured, your medical team will have treatments and suggestions to help deal with them. Here are some approaches for common side effects.
- Hot flashes: Fans, layered clothing, and low-dose antidepressants can help.
- Bone thinning: Calcium, vitamin D, and weight-bearing exercise are your friends.
- Fatigue: Pace yourself; small daily goals beat weekend heroics.
- Erectile changes: Pills, vacuum devices, even tiny injections can restore intimacy.
- Mood swings: These are normal. If sadness lingers for more than two weeks, mention it. Medication or therapy lifts many men back to center.
Questions To Ask Your Doctor
- Is my cancer still hormone-sensitive, or is it shifting toward resistant?
- What’s my current PSA doubling time?
- Would a PSMA PET scan change the plan?
- Which treatment hits the cancer hardest with the least impact on my daily routine?
- How do we protect my heart, bones, and mind while on therapy?
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