“Whack-a-Mole” Result: I am almost 1... - Advanced Prostate...

Advanced Prostate Cancer

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“Whack-a-Mole” Result

jfoesq profile image
35 Replies

I am almost 13 yrs post DX of stage 4 with several Mets. In addition to prostate removal surgery a few months after Dx, and Lupron and Abiraterone, I have had radiation 3X. The first time was in 2014 to my left hip (acetabulum). Then, as PSA started to appear and begin rising to low levels, my left hip was radiated again- this time with more advanced radiation. And, then I had a vertebrae radiated almost 2 months ago as my PSA rose to .32. Following the radiation treatments to my hip, on both occasions my PSA dropped to <.05.

This time, the radiation to one of my vertebrae resulted in a decrease from .32 to .16. Is there any chance/likelihood my PSA will continue to drop 2 months following the radiation or is the best O can hope for?

And- is there any medical support to lend hope that “whack-a-mole” may lead to a longer overall survival?

Thx for your replies.

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Seasid profile image
Seasid

Your experience with targeted radiation lowering PSA aligns with what some studies and anecdotal reports suggest about metastasis-directed therapy (MDT). However, the extent of PSA reduction post-radiation varies. In some cases, PSA may continue to decline for a few months, but often, the nadir (lowest PSA) is reached within 1-3 months post-treatment.

As for the "whack-a-mole" approach—treating individual metastases as they appear—there is some emerging evidence that it might prolong progression-free survival, particularly in patients with oligometastatic disease (a limited number of metastases). The STOMP and ORIOLE trials suggested that MDT could delay systemic therapy, but whether it improves overall survival is still debated. Given your long-term response (13 years post-diagnosis), your case seems to support the idea that aggressive local treatments can help keep the disease at bay.

Your PSA’s decline from 0.32 to 0.16 is a positive sign. It’s possible it could drop further, but if it stabilizes at 0.16, that still indicates some disease control. Continuing regular monitoring with your oncologist will be key to deciding on further treatments. Have you discussed additional systemic options beyond Lupron and Abiraterone with your doctor?

ChatGPT said

Seasid profile image
Seasid in reply toSeasid

The management of oligometastatic prostate cancer through targeted radiation (often referred to as the "whack-a-mole" approach) can be complex, and your case raises several important considerations:

### 1. **PSA Response Post-Radiation**

- **Timing of PSA Decline**: Radiation-induced cell death is gradual, and PSA nadirs (lowest levels) are typically seen **3–6 months after treatment**. At **2 months post-radiation**, it is possible your PSA may continue to decline, though the magnitude of further reduction depends on factors like tumor biology and treatment sensitivity.

- **Previous vs. Current Response**: The smaller PSA drop this time (0.32 → 0.16) compared to prior responses (e.g., post-hip radiation to <0.05) could reflect differences in tumor burden, radiation resistance, or the presence of other untreated micro-metastases. Imaging (e.g., PSMA PET/CT) might clarify if additional lesions are contributing.

### 2. **"Whack-a-Mole" and Survival Outcomes**

- **Oligometastatic Disease Concept**: Treating limited metastases (e.g., ≤3–5 lesions) with stereotactic body radiation therapy (SBRT) is supported by trials like **STOMP** and **ORIOLE**, which show delayed progression and prolonged time on systemic therapy. However, these studies primarily demonstrate **progression-free survival (PFS) benefits**; overall survival (OS) data remain immature.

- **Longer-Term Outlook**: Your 13-year survival with stage IV disease suggests a favorable biology. Aggressive metastasis-directed therapy (MDT) may contribute to this by delaying the need for intensified systemic therapies (e.g., chemotherapy, PARP inhibitors), potentially improving quality of life and OS. However, repeated recurrences may eventually signal a shift to more widespread disease, where MDT becomes less effective.

### 3. **Next Steps**

- **Imaging**: A **PSMA PET/CT** could identify other sites of disease, guiding further MDT or systemic options.

- **PSA Monitoring**: Track PSA every 2–3 months. A continued decline or stabilization would support ongoing MDT; a rise may prompt reassessment.

- **Systemic Therapy**: If PSA rises despite MDT, consider:

- Reinitiating/changing androgen pathway inhibitors (e.g., switching to enzalutamide/darolutamide).

- Genetic testing (e.g., BRCA, HRR mutations) for PARP inhibitor eligibility.

- Clinical trials (e.g., radiopharmaceuticals like Lu-177-PSMA-617).

### 4. **Caveats**

- **Tolerance of Repeated Radiation**: Ensure cumulative radiation doses to critical structures (e.g., bowel, spinal cord) remain within safe limits.

- **Balancing Burden vs. Benefit**: Frequent interventions may impact quality of life; weigh this against potential survival gains.

### Bottom Line

There is **hope** for further PSA decline, and the "whack-a-mole" strategy may contribute to prolonged survival in oligometastatic disease. However, ongoing vigilance with advanced imaging and tailored systemic therapy will be key to optimizing outcomes. Discuss these strategies with your oncologist to align with your goals and preferences.

DeepSeek said

jfoesq profile image
jfoesq in reply toSeasid

Thx. As suggested by Deepseek, I do get regular labs and PSA testy every 3 months and I will have PSMA tests as indicated- which is what led to this and prior detection of “hot tumors” and the radiation to treat them.

dhccpa profile image
dhccpa in reply toSeasid

You tell the OP nadir is reached 1-3 months after radiation. AI says 3-6 months. You're contradicting AI? Remember, the poster is only 2 months after radiation this time.

Same issue with previous response vs. current response. He's only 2 months out at present. Shouldn't he wait to evaluate?

Seasid profile image
Seasid in reply todhccpa

I really don't know.

Seasid profile image
Seasid in reply toSeasid

I just know that if the cancer is really aggressive than it dies quickly after radiation, but if it is less aggressive than it takes much longer. Therefore it all depends on the clones of the cancer present.

Seasid profile image
Seasid in reply toSeasid

Yes, I agree to an extent. More aggressive cancers often have higher proliferation rates, meaning they might respond more quickly to treatments like radiation, leading to an earlier apparent decline in tumor burden. However, this rapid cell kill doesn't necessarily translate to a complete cure since aggressive cancers can also have resistant subpopulations. Conversely, less aggressive tumors might show slower declines because they grow and respond more gradually. Ultimately, the timeline for how quickly cancer cells die following treatment depends on a combination of factors—including aggressiveness, genetic characteristics of the tumor, and treatment specifics.

Tall_Allen profile image
Tall_Allen

"And- is there any medical support to lend hope that “whack-a-mole” may lead to a longer overall survival?" No, but it is a very good question - does it slow the cancer down or merely treat PSA? There is no evidence that whack-a-mole leads to longer survival. It certainly eliminates the biggest sources of PSA (larger metastases put out more PSA), but there is not any evidence that it increases survival. There are some randomized clinical trials running currently that will answer your question in a few years. My attitude has always been: if safe, why not do it?

This explains the problem in more detail:

prostatecancer.news/2020/07...

jfoesq profile image
jfoesq in reply toTall_Allen

That’s my thinking too. Thx

kainasar profile image
kainasar

Someone did a small study comparing PSA progression biomarkers, to radiographic progression for indication of cancer growth.

Seasid profile image
Seasid

The "whack-a-mole" approach in treating oligometastatic prostate cancer involves targeting individual metastases with therapies like radiation or surgery. Here's a structured summary of the key considerations and current evidence:

### **Key Points on "Whack-a-Mole" Approach and Survival**

1. **PSA vs. Survival**:

- **PSA Reduction ≠ Survival Benefit**: Lowering PSA levels by treating visible metastases may reflect local control but does not confirm systemic disease eradication. PSA is a biomarker, not a direct measure of survival.

- **Limitations of PSA**: A small study comparing PSA progression to radiographic progression highlights that PSA changes can diverge from actual tumor behavior. For example:

- PSA might drop post-treatment while undetected micrometastases persist.

- Radiographic progression (new lesions on scans) may occur without significant PSA rises, depending on tumor biology.

2. **Oligometastatic Disease and Clinical Trials**:

- **STOMP and ORIOLE Trials**: These studies show metastasis-directed therapy (MDT) can delay progression and prolong time without systemic therapy. However, **overall survival (OS) data remain inconclusive**.

- **Ongoing Trials**: Randomized trials (e.g., SABR-COMET, others) aim to clarify if MDT improves OS. Results are pending, but current evidence supports progression-free survival (PFS) benefits, not OS.

3. **Biological Considerations**:

- **Microscopic Disease**: Even with effective local treatment, undetected micrometastases may drive systemic progression. Aggressive biology or resistance could limit long-term benefits.

- **Tumor Heterogeneity**: Some metastases may be resistant to radiation, leading to recurrence despite PSA declines.

4. **Safety and Pragmatism**:

- **Risk-Benefit Balance**: If MDT is safe (minimal toxicity, preserved quality of life), it may be reasonable to pursue, even without proven survival gains. It could delay more aggressive therapies (e.g., chemotherapy) and provide psychological benefits.

- **Cumulative Risks**: Repeated radiation requires careful planning to avoid organ toxicity (e.g., bowel, spinal cord).

5. **Imaging Advances**:

- **PSMA PET/CT**: Enhances detection of small metastases, allowing more precise MDT. However, it also raises questions about treating ever-smaller lesions of uncertain clinical significance.

### **Conclusion**

- **No Proven Survival Benefit Yet**: Current evidence supports MDT for delaying progression and managing oligometastatic disease, but not for extending OS.

- **Hopeful but Cautious**: The approach may be justified in select patients (limited metastases, favorable biology) while awaiting trial results. Shared decision-making is critical, emphasizing uncertainties and individualized goals.

### **Practical Takeaway**

- **Monitor Closely**: Use advanced imaging (PSMA PET/CT) alongside PSA to guide therapy.

- **Consider Clinical Trials**: Enrollment may provide access to emerging therapies and contribute to evidence generation.

- **Balance Realism and Optimism**: Acknowledge the lack of OS data but recognize potential benefits in quality of life and delaying systemic therapy.

In essence, "whack-a-mole" is a promising strategy for oligometastatic prostate cancer, but its impact on survival remains unproven. Patients and clinicians should weigh its use against safety, disease biology, and personal priorities.

DeepSeek said

Seasid profile image
Seasid

My first medical oncologist professor Richard Epstein said to me not to use local treatments only systemic therapy.

I was diagnosed as de Novo polymetastatic pc in my bones with distant spread. Professor Epstein also said that xofigo is a local treatment which only treat bone metastasis but not the whole underlying disease. He agreed that ones far down the road I start experiencing bone pain it is ok then to use xofigo for pain control.

Now I am aware that metastasis directed therapy is fine if you can do it safely but I am aware that with radiation always can something go wrong. Therefore it is better for me now after 7 years to start abiraterone plus prednisolone and maybe combine it with SBRT irradiation of the metastasis if it is safe to do so rather than just to rely on SBRT irradiation alone. Cancer is a systemic disease and even if you kill the majority of the local cancer some to the radiation resistant strains could survive without escalating the systemic therapy.

Because now, seven years after my diagnosis I am stable on bicalutamide plus ADT alone the next step if my PSA starts to rise will be to decide what is best for me, only to add abiraterone plus prednisolone or also to radiate my local metastasis if it is safe to do so?

I would like to proceed with escalation of my systemic therapy to Abiraterone plus prednisolone and then wait and see if I need a MDT or not. I am not a doctor but I don't want to disregard what I was told by professor Richard Epstein just because now it is cool to use high precision MRI Linac Elekta Unity machine for killing a metastasis.

Fortran1958 profile image
Fortran1958

I was oligometastatic with 2 lesions and PSA of 0.66 when PSMA finally identified target. I had 5 targeted radiotherapy treatments 9 years after my RALP. 3 months later my PSA was 0.02 and then after a further 3 months it was 0.01. Continuing to monitor every 3 months.

Seasid profile image
Seasid in reply toFortran1958

Great 👍

kiteND profile image
kiteND

This is a great question. My doc at Mayo has me on "whack-a-mole." My local MO defers to that approach -- and my decision -- but believes there is no evidence that the approach has a better survival rate. I personally do not like the idea of letting known mets grow.

Survivor1965 profile image
Survivor1965

I don’t have answers to your questions but just the parallels of our situation are crazy. I started in 2012 stage four.

Cooolone profile image
Cooolone

I believe, Whack-a-Mole coupled with systemic therapy, even if short term (chemo) is the ultimate benefit/risk reward in regard to advanced diagnosis (StgIV) patients.

I'll never know, as I wasn't diagnosed with mets then, but post RP I was persistent PSA, crazy 2x time, went with the SOC of 40 IMRT to prostate bed and surrounding nodes. Interestingly, NOT a hot spot by the bladder. Only lasted less than a year, persistent PSA with crazy 2x again, found mets by accident as PET scan wasn't overly avid, suspect inflammation, not PCa. But mets found with attempt at an Appendectomy!? Of all things... So the mets (seen) were removed and had chemo and ADT (life). Lasted around a year again... PET scan this time, still low avidity, showed that Bladder hot spot, a spot where my Colon was resected, and lung modules that were always there, never avid, now were. So Whack-a-Mole it was! Radiation delivered to all three spots! And so far (knock on wood), things are quiet!

I will insist on any future mets, hotspots be treated immediately! Only when it might get completely out of hand go to systemic therapy again. Reserve that... And I pray to God this isn't for a very long long time!...

Best of Luck and Regards to all!

SsgCulldelight profile image
SsgCulldelight

Hi looks like you went through most of the options, and that u made it through radiation days Enough. Everything after that is a piece of cake my friend. Understand you let them kill off Most of your good cells with the mutated cells and made I it back from that. Your aSuperMan of no one told you in telling you YOU are aSuperMan. Now adjust your diet, drink reverse osmosis water, and stop absolutely stop SUGAR intake. We all like a honey bun or donut every once in a while so do treat yourself once in a while. Otherwise follow your ADT plan my friend and just know this some side effects is better than not living, in most cases🤣 and sex is great but in sure you've had your share of poompoom by now and someone else's to likely. Trek your wife to chill which hopefully she understands the lack of sex drive and a capable pp😅don't mind mi decorum rite now in havin a Grand old time without cussin. Go njoi your life bro, hug the kids go swimming or hunting out whatever, don't make excuses not to do stuff because your psa is a Lil wonky, or the dr gives you iffy news about your progress or digress. J just go live my man. Love n light Ssg. Cullum

j-o-h-n profile image
j-o-h-n

Nowadays everyone wants to "Whack-a-Mole”. In my much younger days I always was looking to "Whack-a-Hole".......

Good Luck, Good Health and Good Humor.

j-o-h-n

Cancer2x profile image
Cancer2x in reply toj-o-h-n

Golfer, huh?

j-o-h-n profile image
j-o-h-n in reply toCancer2x

In those days. more like a Go-fer as much as I could.

Good Luck, Good Health and Good Humor.

j-o-h-n

jfoesq profile image
jfoesq in reply toj-o-h-n

Thx

Cancer2x profile image
Cancer2x

Good luck! I just whacked a coupla moles in my abdominal lymph nodes with CT/SBRT. PSA dropped twice from that treatment, measured three months apart, now down to 1.0! Next test is next week. Hope to see a continued drop then to below 1.0!

jfoesq profile image
jfoesq in reply toCancer2x

Thx for letting me know. Good luck

Rocketman1960 profile image
Rocketman1960

Ant time you can lower the tumor burden that’s a good thing. I have also done SBRT several time over the past 14.5 years. Keep kicking the can down the road.

jfoesq profile image
jfoesq in reply toRocketman1960

Thx

DaveKY profile image
DaveKY

Your journey seems to be much better than most. Your story sounds a lot like mine, but my numbers are astronomically greater (1900 PSA) and in only 5 years. Abiraterone worked great for 3 years with a drop from my original PSA at DX of 106 to 0.04 but the crazy moles kept popping up with 4 radiation doses. After Abiraterone came Lynparza with little help and chemo with almost no help. I just started Xofigo which is good for bone mets. Xofigo may be in your future, but so far it sounds like you and your team have it well managed.

speranza10 profile image
speranza10 in reply toDaveKY

What other treatments did you do before xofigo?

DaveKY profile image
DaveKY in reply tosperanza10

Zytiga, a few doses of radiation, Lynparza, then a couple different chemos. No Xtandi.

DaveKY profile image
DaveKY in reply toDaveKY

And Lupron every 3 months.

speranza10 profile image
speranza10 in reply toDaveKY

Good luck with xofigo, I hope it works well for you.

speranza10 profile image
speranza10 in reply toDaveKY

By any chance, in addition to Zytiga, have you also tried Xtandi?

jfoesq profile image
jfoesq in reply tosperanza10

I have never been on Xofigo nor Xtandi? Maybe one of those will be prescribed to me in the future.

speranza10 profile image
speranza10 in reply tojfoesq

Good for you, you still have many options, good luck I wish you the best.

jfoesq profile image
jfoesq

Good luck to you

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