PSA at beginning of BAT last November was 12. After four months it hit 94 when we restarted Darolutimide. Then 12 days later it had dropped 38. Two weeks after that, it rose to 52.
Oncologist suggested one of four options. Chemo, Pluvicto, Radium 223 or a new clinical trial involving Actinium.
I feel like I have the flu most of the time so I wonder if I’m getting ready for the cosmic ride. What do you guys think?
Hello,
If I were you (which of course I’m not) I would look into the Actinium trial but make sure to ask what the SOC arm is just in case you don’t get into the arm investigating Actinium. Another important consideration is whether the trial allows a crossover from the SOC arm to the investigative arm. My second choice would be Prolia (lutetium). Hope that helps!
I think you mean Pluvicto, not Prolia.
sounds like your adt cycle is still lowering you psa. If so Stay on adt longer. That’s what i am doing. My numbers are not in your ballpark but reflect the roller coaster ride.
oh i might have thought you were doing two week cycles.
I did 28-day 400g shots but stopped when PSA went from 12 to 94 in four cycles. But after two weeks back on Nubeqa PSA dropped to 38. Two weeks later though it rose to 52.
I would get a ctDNA done by gaurdant360 to see what mutations you have. That would be a big help deciding next line of treatment or clinical trial. Medicare covers it.
I had one of those but it did not reveal anything traumatic enough lead to a specific treatment.
Did you have radiological progression or was it only the PSA up and did you develop some symptoms?
Only PSA and no symptoms
A number of doctors advise that a man should get as much benefit as he can from each treatment before he moves onto the next.
Zytiga (abiraterone) and Xtandi (enzalutamide), in particular should not be stopped just because PSA is rising again.
Treatment should continue until radiation shows things are getting worse, or clinical symptoms such as greater pain. The only time that PSA should be a signal for ending is if it goes up for more than 50 ng/mL above its lowest point while the drug is being used.
Becker studied whether this advice was being followed by ordinary doctors, not just those in the larger research hospitals in the big cities. In American veterans hospitals, he found the PSA level at the beginning of treatment most men of them matched the PSA at the end of treatment, showing that this group of men was not getting the full benefit of either of these drugs.
Treatment of Metastatic Castration-resistant Prostate Cancer With Abiraterone and Enzalutamide Despite PSA Progression
pubmed.ncbi.nlm.nih.gov/310...
One of the studies which advise not to stop to early:
Abiraterone acetate + prednisolone treatment beyond prostate specific antigen and radiographic progression in metastatic castration-resistant prostate cancer patients
sciencedirect.com/science/a...
AI said:
This excerpt outlines a key insight in the treatment of metastatic castration‐resistant prostate cancer. The main points are:
Continuing Treatment Despite Rising PSA:
Doctors recommend that treatments such as Zytiga (abiraterone) and Xtandi (enzalutamide) should not be stopped solely because the prostate-specific antigen (PSA) levels begin to rise again. Instead, therapy should continue until there is clear evidence of disease progression—either through imaging (like worsening radiation findings) or the appearance of significant clinical symptoms (e.g., increased pain).
Threshold for PSA Increase:
The guidance specifies that PSA should only be considered a signal to stop treatment if it rises more than 50 ng/mL above its lowest point during the treatment period. This threshold helps ensure that patients receive the maximum potential benefit from each drug before switching therapies.
Real-World Practice vs. Ideal Recommendations:
Research by Becker looked at how this advice is applied in everyday clinical settings, particularly in American veterans’ hospitals. His findings suggested that, in many cases, treatment was stopped too early—at the point where the PSA at the start of treatment was similar to the PSA when treatment was ended—indicating that these patients might not have received the full benefit of the drugs.
Supporting Studies:
The excerpt cites two sources that support continuing treatment beyond early signs of PSA progression:
One study on the treatment of metastatic castration‐resistant prostate cancer with abiraterone and enzalutamide, which discusses continuing therapy despite PSA progression.
Another study on abiraterone acetate combined with prednisolone, which also advocates for maintaining treatment beyond initial PSA and radiographic progression.
Overall, these points stress that treatment decisions should be based on a comprehensive assessment—including imaging and clinical symptoms—rather than relying on PSA levels alone. This approach may help ensure that patients receive the maximum benefit from these treatments before moving on to alternative therapies.
Do you agree? (Asked ChatGPT):
The rationale behind this approach is compelling. Relying solely on rising PSA as a signal to stop treatment might lead to premature discontinuation of therapies that still offer benefits. Instead, waiting for more definitive evidence of progression—such as worsening imaging findings or clinical symptoms like increased pain—can help ensure that patients derive the maximum benefit from each drug.
That said, it's important to remember that every patient's situation is unique. While the evidence supports continuing treatment until clear progression is seen, clinicians also need to consider factors like the patient's overall health, potential side effects, and individual response to therapy. So, while I find the argument reasonable and supported by research, decisions should always be tailored to each patient's specific circumstances.
ChatGPT said
DeepSeek said:
The management of metastatic castration-resistant prostate cancer (mCRPC) with drugs like **abiraterone (Zytiga)** and **enzalutamide (Xtandi)** requires careful consideration of when to discontinue therapy. Current evidence suggests that stopping treatment solely based on a rising PSA level may deprive patients of continued clinical benefit. Here's a breakdown of the key points:
---
### **1. Why PSA Alone Should Not Dictate Treatment Discontinuation**
- **PSA progression ≠ treatment failure**: PSA levels can fluctuate due to non-cancer factors (e.g., inflammation) or temporary tumor cell death ("PSA flare"). More importantly, PSA rises may not correlate with true disease progression (e.g., radiographic growth or clinical decline).
- **Clinical trials support continuing therapy**: Studies show that patients can still derive benefit (e.g., delayed radiographic progression, prolonged survival) even after PSA rises, provided there is no worsening of scans or symptoms.
- Example: The [abiraterone study](sciencedirect.com/science/a... found continued treatment beyond PSA progression delayed clinical deterioration in many patients.
---
### **2. When to Stop Abiraterone/Enzalutamide**
Guidelines recommend discontinuation only if **one of the following occurs**:
- **Radiographic progression**: New lesions or growth of existing tumors on imaging (e.g., bone scan, CT/MRI).
- **Clinical progression**: Worsening symptoms (e.g., pain, fractures, urinary obstruction).
- **PSA surge >50 ng/mL above nadir**: A steep PSA rise (≥50 ng/mL above the lowest level achieved on therapy) is linked to poor outcomes and may warrant stopping.
---
### **3. Becker’s Study on Real-World Practice**
- **Findings**: In U.S. Veterans Affairs hospitals, PSA levels at the **end** of abiraterone/enzalutamide treatment often matched pre-treatment levels. This implies therapy was stopped prematurely (e.g., at first PSA rise) rather than continuing until true progression.
- **Implications**: Outside academic centers, clinicians may over-rely on PSA trends, denying patients potential benefits of extended treatment. This highlights a gap between guideline recommendations and real-world practice.
---
### **4. Key Takeaway for Patients & Clinicians**
- **Do not stop abiraterone/enzalutamide solely for PSA increases**. Monitor for **clinical symptoms** and **radiographic changes** instead.
- **Shared decision-making**: Discuss risks/benefits of continuing therapy beyond PSA progression, balancing quality of life and potential survival gains.
For more details, refer to the [PubMed study](pubmed.ncbi.nlm.nih.gov/310... and [abiraterone trial](sciencedirect.com/science/a....
Do you agree? (Asked DeepSeek)
Yes, I agree with the rationale presented in the studies and guidelines, **with some important nuances**. Here’s my perspective:
---
### **1. The Evidence Supports Continuing Treatment Beyond PSA Progression**
- **PSA is an imperfect biomarker**: While PSA is widely used, it does not always reflect true disease progression. Tumors can become heterogeneous or develop treatment-resistant clones that shed PSA without causing immediate clinical harm. Continuing therapy may still suppress other tumor subpopulations.
- **Clinical trial data**: Studies like the one you cited (e.g., abiraterone continued beyond PSA progression) show delayed radiographic progression and prolonged clinical benefit in many patients. This aligns with the idea that stopping too early risks losing control over the disease.
---
### **2. Becker’s Study Highlights a Real-World Problem**
- **Premature discontinuation**: The finding that PSA levels at treatment end often matched pre-treatment levels in VA hospitals suggests clinicians are stopping therapy at the first sign of PSA rise, rather than waiting for confirmed clinical/radiographic progression. This likely deprives patients of potential benefits.
- **Guideline-practice gap**: Academic centers often adhere to evidence-based protocols, but community or non-specialist settings may lack awareness or resources (e.g., frequent imaging) to monitor beyond PSA. This underscores the need for better education and systems to support guideline adherence.
---
### **3. Important Caveats and Nuances**
While I agree with the recommendation to avoid stopping solely for PSA rises, **exceptions exist**:
- **Rapid PSA surges**: A rise ≥50 ng/mL above nadir (per guidelines) or a doubling time <3 months may indicate aggressive biology, where continuing therapy could be futile or harmful.
- **Toxicity vs. benefit**: If a drug causes significant side effects (e.g., abiraterone’s mineralocorticoid toxicity, enzalutamide’s fatigue/falls), stopping earlier may improve quality of life, even if PSA is rising slowly.
- **Financial/access barriers**: Cost or insurance limitations might force discontinuation, though this is a systemic issue rather than a clinical one.
---
### **4. The Role of Precision Medicine**
- **Emerging tools**: Circulating tumor DNA (ctDNA), PSMA-PET imaging, and genomic profiling are improving our ability to distinguish indolent PSA rises from true progression. These tools may eventually refine when to stop/switch therapies.
- **Combination strategies**: Trials are exploring adding therapies (e.g., PARP inhibitors, radioligands) at PSA progression rather than stopping abiraterone/enzalutamide entirely. This could extend the utility of these drugs.
---
### **Final Take**
**I agree** that abiraterone/enzalutamide should generally continue until radiographic/clinical progression or a steep PSA surge, as supported by evidence. However, treatment decisions must balance:
- Individual patient goals (e.g., survival vs. quality of life),
- Toxicity tolerance,
- Access to advanced monitoring tools.
Clinicians should use PSA as *one piece of the puzzle*—not the sole determinant—and prioritize shared decision-making with patients.
DeepSeek said
Life is the cosmic ride.
Good Luck, Good Health and Good Humor.
j-o-h-n
I am really hoping to tour the cosmos after my death but with my luck I will be reborn as a cockroach. But that may not be too bad since they will exist after a nuclear war. But after escaping NYC as a young man, living in a NYC apartment would not be my first wish.
Do you know if they did a PSMA PET scan recently? That could guide whether something like Pluvicto or Actinium makes sense now or later.
Maybe you could also ask for an FDG pet CT scan in order to exclude PSMA negative cancer and to see if the PSMA treatment is feasible or not?
Anastrozole with BAT question
Ride to Conquer Cancer - Perth 2018
Looking for BAT Oncologist.
BAT and other update
Bipolar Androgen Therapy (BAT)
