A common treatment for prostate cancer is radical prostatectomy (RP), where the prostate gland is surgically removed. After surgery, doctors monitor your prostate-specific antigen (PSA) levels to watch for signs of the cancer coming back. If the PSA level becomes detectable, it’s called biochemical recurrence (BCR).
In the past, “detectable” might have meant any reading above zero. Now, doctors often use a threshold of 0.03 ng/mL or higher to define BCR.
If your PSA level rises immediately after surgery, that’s obviously a concern. However, some men have undetectable PSA levels for a while, only to see it rise later. This is sometimes called “delayed detectable PSA” or “delayed biochemical recurrence,” and it’s generally defined as a detectable PSA level more than six months after surgery.
What does it mean if you have a PSA level that remains undetectable after 3 years, but then rises? That’s what we’ll explore in this article. We’ll look at the natural history of this situation, what factors might influence it, and how doctors typically manage it. We’ll also examine long-term outcomes like metastasis-free survival (MFS), prostate cancer-specific mortality (PCSM), and overall survival.
Specifically, we’ll look at the characteristics of men who experience this delayed PSA recurrence, what influences treatment decisions, and how effective salvage therapies are in these cases.
Defining Undetectable PSA and Delayed Biochemical Recurrence
Okay, let’s break down what we mean when we talk about “undetectable PSA” and “delayed biochemical recurrence” (BCR) after prostate cancer treatment.
What Constitutes “Undetectable” PSA?
First, “undetectable” doesn’t always mean zero. It means the level of prostate-specific antigen (PSA) in your blood is below what the lab test can reliably measure. These days, we have pretty sensitive PSA tests, but they still have their limits. The exact lower limit of detection can vary a little depending on the specific test your doctor uses.
Even a very low PSA level, like less than 0.03 ng/mL, isn’t necessarily a guarantee that everything’s clear. It could still signal that there’s some residual cancer or that the cancer has come back. That’s why doctors keep a close eye on PSA levels over time.
Defining Delayed Biochemical Recurrence
Now, what about “delayed BCR?” This refers to a rise in PSA after a period where it was undetectable. And when we talk about “delayed,” we usually mean at least three years of undetectable PSA. This is different from “immediate BCR,” where the PSA starts to rise within the first few months after surgery (radical prostatectomy, or RP).
Why three years? Well, after surgery, there might be a tiny bit of normal prostate tissue left. This tissue can still produce some PSA. Waiting three years gives that tissue a chance to disappear, so any PSA rise after that is more likely to be a sign of true cancer recurrence rather than just leftover benign tissue doing its thing.
Natural History of Delayed PSA Recurrence
It’s important to understand why a PSA recurrence might be delayed, and what that means for a patient’s long-term outlook.
Factors Influencing Delayed PSA Recurrence
There are several reasons why a rise in PSA might not be detected right away after treatment:
- Microscopic residual disease: Sometimes, tiny amounts of cancer cells remain after surgery or radiation, but they’re not enough to significantly raise PSA levels initially.
- Slow-growing tumors: Some prostate cancers are slow-growing. These tumors might take a long time to become large enough to produce a detectable PSA increase.
- Adjuvant or early salvage radiotherapy: Radiation therapy given after surgery (adjuvant) or when PSA starts to rise (early salvage) can effectively delay recurrence by killing off remaining cancer cells.
Patient-specific factors also play a role. For example, a patient’s pre-operative PSA level, Gleason score (which indicates how aggressive the cancer cells look under a microscope), pathological stage (how far the cancer has spread), and whether the surgical margins were clear all influence the likelihood and timing of recurrence.
Risk Stratification and Prognostic Factors
Doctors use risk stratification tools to assess a patient’s prognosis after initial treatment. These tools help predict the likelihood of recurrence and guide treatment decisions.
Some common tools include:
- CAPRA-S score: This score uses factors like PSA level, Gleason score, and stage to estimate the risk of recurrence and metastasis (spread of cancer to other parts of the body).
- Decipher score: This genomic test analyzes the activity of certain genes in the tumor to predict long-term outcomes and help doctors decide whether additional treatment is needed.
PSA doubling time (PSA-DT) is another important factor. PSA-DT measures how quickly the PSA level is rising. A shorter PSA-DT (less than 6 months) often indicates a more aggressive cancer and a higher risk of recurrence after salvage therapy. A longer PSA-DT may suggest a less aggressive, or indolent, disease course.
Diagnostic Workup and Monitoring
So, your PSA is undetectable, and you feel like you’re in the clear. But what happens when it starts creeping up again after 3 years? Here’s what you need to know about getting checked out and staying on top of things.
Initial Evaluation Upon PSA Detection
Okay, so your PSA is detectable again. What’s next? Your doctor will likely recommend some tests to figure out what’s going on. These might include:
- Multiparametric MRI: This gives a detailed look at your prostate and the surrounding area to see if the cancer has come back locally.
- Bone scan or PSMA PET/CT scan: These scans help detect if the cancer has spread to other parts of your body (distant metastasis).
It’s super important to have an open conversation with your doctor about these tests. What are the risks and benefits? What are we hoping to find? Your preferences, other health issues, and how likely we are to find something that we can actually do something about all play a role in deciding how far to take the workup.
Frequency of PSA Monitoring
Once your PSA is detectable, you’ll need to get it checked regularly. How often depends on a few things, especially how quickly your PSA is rising (PSA-doubling time or PSA-DT). If it’s rising fast, you’ll need more frequent monitoring.
It’s not just about the PSA number itself, but how it’s changing over time. A PSA that’s shooting up quickly is more worrisome than one that’s creeping up slowly. We need to keep an eye on the overall trend to get a good picture of what’s happening.
Treatment Options and Considerations
So, you’ve had your prostate removed, and now you’re dealing with a rising PSA. What’s next? Luckily, there are several treatment options to consider, and the best approach depends on your individual situation.
Surveillance
For some men with a slow PSA rise after surgery, “active surveillance” might be a reasonable option. This basically means keeping a close eye on things with regular PSA tests and imaging, without rushing into further treatment. Good candidates for surveillance often have a low Gleason score (indicating less aggressive cancer), a long PSA doubling time (PSA-DT), and no signs that the cancer has spread (metastasis).
The upside of surveillance is avoiding unnecessary treatment and the potential side effects that come with it. The downside is that the cancer could progress while you’re watching and waiting, potentially making later treatment less effective. It’s a balancing act that you need to discuss thoroughly with your doctor.
Salvage Radiotherapy
If your PSA is rising and the cancer seems to be localized (meaning it hasn’t spread beyond the prostate bed), salvage radiotherapy is often the next step. This involves using radiation to target any remaining cancer cells in the area where the prostate used to be.
Timing is key with salvage radiotherapy. Generally, the earlier you start radiation after your PSA starts to rise, the better the chances of controlling the cancer long-term. Your doctor will also determine the appropriate dose of radiation. Studies have shown that salvage radiotherapy can be very effective at controlling PSA levels and preventing the cancer from spreading.
Sometimes, doctors will also recommend adding androgen deprivation therapy (ADT) to salvage radiotherapy. ADT lowers the levels of testosterone in your body, which can help to slow down the growth of prostate cancer cells. ADT can improve outcomes, but it also comes with side effects like fatigue, loss of libido, and bone thinning, which can impact your quality of life and sexual health after treatment. Again, it’s a risk-benefit discussion you need to have with your doctor.
Systemic Therapies
If the cancer has already spread to other parts of the body (distant metastasis), or if you’re not a good candidate for local treatments like surgery or radiation, systemic therapies are usually the focus. These treatments work throughout your entire body to target cancer cells wherever they may be.
ADT is a common systemic therapy. There are also newer hormonal agents like abiraterone and enzalutamide that can be effective even when the cancer has become resistant to traditional ADT. Chemotherapy is another option for more aggressive or advanced disease. And finally, immunotherapy is an emerging treatment approach that harnesses the power of your own immune system to fight cancer.
Outcomes and Prognosis
So, what can you expect if you have a delayed biochemical recurrence (BCR)? What do studies show about long-term survival?
Metastasis-Free Survival (MFS)
Metastasis-free survival refers to the length of time after treatment that a person lives without the cancer spreading to other parts of their body.
The good news is that MFS rates in patients with delayed BCR can be excellent, even without immediate salvage therapy. In other words, even if you wait to get more treatment, you can still have a good outcome.
These MFS rates are often compared to those with immediate BCR (where the PSA rises quickly) and those receiving tertiary treatment (further treatment after salvage therapy).
Factors that contribute to improved MFS include early detection and treatment of the recurrence, as well as favorable characteristics of the original tumor.
Prostate Cancer-Specific Mortality (PCSM) and All-Cause Mortality (ACM)
Prostate cancer-specific mortality refers to death specifically from prostate cancer, while all-cause mortality refers to death from any cause.
Studies generally show that delayed BCR is associated with lower PCSM and ACM compared to immediate BCR. This means that if your PSA rises slowly after initial treatment, you’re less likely to die from prostate cancer or any other cause compared to someone whose PSA rises quickly.
Several factors can influence PCSM and ACM, including how well salvage therapies work, the presence of other health conditions (comorbidities), and the patient’s age and overall health.
Comparison to Immediate BCR and Undetectable PSA Groups
It’s helpful to compare outcomes between patients with delayed BCR, immediate BCR, and those who maintain an undetectable PSA level after initial treatment.
Generally, patients with delayed BCR have a more favorable prognosis compared to those with immediate BCR. While not as good as maintaining an undetectable PSA, a delayed recurrence still suggests a slower-growing, less aggressive cancer.
Unique Considerations and Future Directions
Managing prostate cancer is an evolving field, and there are always new avenues to explore when it comes to monitoring and treatment.
The Role of Novel Imaging Techniques
Traditional imaging techniques have their limits. That’s why researchers are constantly looking for better ways to spot early signs of recurrence. PSMA PET/CT imaging is one promising technique. It’s potentially more sensitive and specific than what we’ve used in the past, which could help doctors make more informed decisions about treatment.
Liquid biopsies, which look at circulating tumor cells or DNA in the blood, are another area of interest. These could potentially help us detect resistance to treatment early on and tailor treatments to the individual. We’re talking personalized medicine here.
Personalized Treatment Approaches
Speaking of personalized medicine, it’s becoming increasingly clear that one-size-fits-all approaches aren’t always the best. We need to consider each patient’s unique characteristics and the specific biology of their tumor when making treatment decisions. That might mean integrating genomic information, like a Decipher score, into the planning process.
And, of course, there’s always the potential for new and improved therapies. Researchers are constantly working to develop novel treatments that target specific molecular pathways involved in prostate cancer. The future is looking bright, but it’s going to take a lot more research to get there.
Frequently Asked Questions
What is the lowest PSA you can have?
The lowest possible PSA level is considered undetectable, often reported as less than 0.03 ng/mL or 0.01 ng/mL depending on the sensitivity of the test. However, even at these very low levels, PSA can still be present.
What cancer did Princess Kate have?
Information about Princess Kate’s cancer diagnosis has been kept private. I am unable to provide further information.
What PSA level is considered undetectable?
An undetectable PSA level typically means the PSA is below the limit of detection for the assay used, often below 0.03 ng/mL or 0.01 ng/mL. This is usually the goal after treatment for prostate cancer, like surgery or radiation.
What is an alarming PSA number?
What constitutes an “alarming” PSA number depends on several factors, including age, race, and family history. Generally, a PSA level above 4.0 ng/mL is considered elevated and warrants further investigation, but your doctor can best interpret your test results.
What is the best drink to lower PSA?
There isn’t a single “best” drink to lower PSA levels. Some research suggests that green tea and pomegranate juice may have beneficial effects on prostate health, but more studies are needed. Maintaining a healthy diet and lifestyle is generally recommended.
Closing Thoughts
So, what have we learned about a PSA level that stays undetectable for three years after prostate surgery? Well, the good news is that a delayed rise in PSA (biochemical recurrence, or BCR) is usually a better sign than an immediate one. It suggests the cancer might be slower to return, or less aggressive. However, just because it’s delayed doesn’t mean it can be ignored. Doctors still need to keep a close eye on things and figure out each patient’s individual risk.
That brings us to the importance of personalized treatment. Every person is different, and every prostate cancer is different. The best approach depends on a whole bunch of factors, from the original tumor characteristics to the patient’s overall health and preferences. It’s essential for doctors and patients to work together to make the right choices about monitoring and treatment.
The field of prostate cancer research is moving fast. New and improved imaging techniques, liquid biopsies (blood tests that can detect cancer cells or DNA), and targeted therapies are on the horizon. These advances offer hope for even better ways to detect, monitor, and treat prostate cancer in the future.
The bottom line is that we need to keep learning. More research is needed to figure out the best ways to manage patients who experience a delayed PSA recurrence after prostate surgery, with the goal of improving their long-term health and quality of life.