Anyone here have a male dog? I have two young ones. I noticed with both that after they were neutered, once they recovered from the surgery the dominance behaviour, furniture-chewing, and high energy persisted. I thought WTF did we spend all that money on this for?? Then like magic, maybe 6 to 9 months after the castration, they became more docile and had lower energy. It was almost as if a switch had flipped.
I hit that point on ADT about 7 months ago. I'd managed ok on doublet therapy for 18 months (Zoladex and Nubeqa), staving off dire fatigue with regular exercise and caffeine. But despite this it was like I'd hit a wall, and caffeine just made me "tired-wired" rather than allowing me to keep up with a busy life. My sleep quality also suffered tremendously, and I'd wake up after 4 hours and be unable to get back to sleep. The absolute WORST though is the stiffness and soreness in my joints, especially my ankles. I'm hobbling around most days now, with hampered mobility. I wasn't expecting this kinda thing for at least another 20-30 years (I shouldn't be unable to walk at 50!)
By June, I brought up the A-DREAM study at Dana-Farber and intermittent ADT to my MO, and she told me flat out "It's not standard of care". By the end of the appointment she'd softened her stance however, asking me to "At least wait until the 2-year mark" of hormone blockade. In the fall, she de-intensified my treatment by keeping me on ADT, but reducing my Nubeqa from 4 pills to 2 pills per day - this failed to help the situation.
That 2-year mark was November 25th, and I've honoured my MO's request! I've decided to start intermittent ADT on January 1st, ringing in the new year medication-free. I'll be having my PSA tested every 3 months, and getting CT and bone scans next June, similar to the parameters of A-DREAM.
I'm excited to start this new treatment path, but I'm also scared sh**less. There's something terrifying about stripping off the SOC security blanket, which has kept my PSA undetectable for 19 months now, and going without it. I know this could fail miserably, but there's also a good chance that I'll feel like myself again, and not be so frazzled and zombified on a daily basis. I have to at least see how it goes, and take that risk.
Written by
32Percenter
To view profiles and participate in discussions please or .
I guess the little punks had so much T in their systems already that it took 9 months to run out! Or it was just in their nature to be little troublemakers.
It’s not the lack of T, but the lack of estrogen made from T. It took 9 months for me for my energy, joint pain to show up and that was when my E2 dropped to <5 from 20pg/dl
I finally convinced my OC to prescribe low dose 0.025mg E2 patch once a week.
My energy had dramatic improvement in 1st week, my joint pains are gone, my mental outlook has improved, bone density should be better, my skin has not improved so i suspect that is a T issue.
I will be going back on BAT once my PSA drops to <0.05. That should be in one week.
By the way my puppy got spayed at 6 months and was suffering from low T thus low E so i did a bunch of research and found an fda approved protocol called dogosterone by a dr Beiber. Also look up dr becker. All it is is a testosterone cypinate injection once a month to replace what the vet took out in the spaying procedure.
She is so much happier now, not scared /spooked anymore and im sure she won’t get incontinence, Cushing syndrome, bone fractures, and best of all i am giving her the 5 years of her life she would have lost without T & E.
Male dogs can be trickier because of their aggressive behavior, but you don’t have to give them all their testosterone back just enough to prevent all the health and life shortening issues.
My two cents as a 6+ year Lupron user, is to recommend that you get your PSA checked monthly, even if you have to pay for it. Ulta labs.com (no space) has excellent pricing on PSA tests.
Initially my MO's Fellow wanted to do monthly PSA tests, then dialled it back to every 3 months as per A-DREAM protocol.I'm comfortable with checking it quarterly for now. As it'll take time for test to come back, there shouldn't be any wild PSA surprises in the first few months. There's also the risk of getting anxiety over minor fluctuations month to month, like when you weigh yourself every day on a diet - "Up by half a pound over yesterday?? Why has my diet FAILED"
Intermittent androgen deprivation therapy (iADT) versus continuous androgen deprivation therapy (cADT) in a younger person with aggressive prostate cancer is a complex and nuanced topic. Let’s delve into the medical basis, evidence, and considerations for this decision:
---
Medical Background
Androgen deprivation therapy (ADT) is a cornerstone treatment for advanced prostate cancer. It works by reducing testosterone levels, slowing the growth of prostate cancer cells. However, it is associated with significant side effects, including:
Fatigue
Loss of libido
Bone thinning (osteoporosis)
Cognitive decline
Metabolic changes (e.g., weight gain, diabetes, cardiovascular risks)
Muscle wasting
Joint pain and stiffness
Continuous ADT (cADT): Patients remain on ADT indefinitely, maintaining a suppressed testosterone level.
Intermittent ADT (iADT): Treatment cycles alternate between on-treatment and off-treatment periods. Testosterone levels recover during the off-period, potentially improving quality of life (QoL).
---
Evidence for iADT vs. cADT
1. Clinical Trials and Key Studies
A-DREAM Study: This trial focused on iADT as a viable alternative to cADT, showing that intermittent therapy could maintain oncological control while offering better QoL. Patients with non-metastatic or low-volume metastatic prostate cancer particularly benefited.
SWOG 9346 (Hussain et al., 2013): In this large study, patients with metastatic prostate cancer on iADT had comparable overall survival to those on cADT. However, iADT significantly improved QoL measures, including sexual function, vitality, and emotional well-being.
EORTC 30985 Study: Another pivotal trial suggesting non-inferiority of iADT in survival outcomes for selected patient populations, although younger and high-risk patients were not the primary focus.
2. Oncological Outcomes
Survival Rates: In appropriately selected patients (non-metastatic, biochemical recurrence, or low-volume metastatic disease), survival outcomes for iADT and cADT are comparable.
Aggressive Cancer: Younger patients, like a 50-year-old, often have more aggressive prostate cancers. Evidence suggests that continuous therapy might provide superior tumor control in this group, as aggressive cancers may not "pause" during off-treatment periods.
3. Quality of Life
iADT offers improved QoL during off-treatment intervals. Testosterone recovery reduces fatigue, improves libido, mitigates joint pain, and helps with bone health.
Side effects of cADT tend to worsen over time due to sustained testosterone suppression.
---
Considerations for a 50-Year-Old with Likely Aggressive Cancer
1. Cancer Aggressiveness
Young patients often have high-risk or very aggressive disease. Aggressive cancers are more likely to progress quickly during off-treatment periods in iADT.
Monitoring becomes critical with iADT. PSA doubling time, imaging, and other biomarkers must be evaluated frequently (every 2-3 months).
2. Treatment Goals
Curative Intent: If the disease is potentially curable (e.g., localized or biochemical recurrence after surgery/radiation), cADT may be preferred for maximum suppression.
Palliative Intent: For advanced disease where long-term survival is the goal, iADT may be a reasonable strategy to balance tumor control and QoL.
3. Duration of ADT
For a young patient, long-term hormonal suppression (as with cADT) might lead to debilitating side effects that impair functional independence in later life.
Intermittent therapy offers periodic relief, allowing recovery of energy and testosterone-dependent functions, but at a potential cost of increased tumor progression risk.
4. Personalization
Genomic Testing: Assessing the molecular profile of the cancer (e.g., BRCA mutations, androgen receptor variants) could provide insights into the likelihood of progression during off-treatment periods.
Imaging: Advanced imaging like PSMA-PET/CT can guide decisions by identifying micrometastatic disease.
Patient Priorities: Involvement in shared decision-making is critical. Some patients prioritize QoL over absolute survival.
---
Key Comparisons
---
Recommendations for a 50-Year-Old
Given the likely aggressiveness of the cancer:
1. Start with cADT: If the cancer is high-risk or aggressive, beginning with continuous therapy provides better disease control. This strategy is especially important for maintaining a longer progression-free survival.
2. Transition to iADT After Disease Stabilization: After a defined period (e.g., 18-24 months), if the PSA remains undetectable, consider transitioning to iADT. This approach balances tumor control with QoL improvement.
3. Close Monitoring: Regular PSA testing (every 2-3 months during iADT), bone scans, and advanced imaging are essential to detect progression early.
4. Lifestyle Support: Focus on exercise, diet, and bone health measures to mitigate the side effects of any ADT strategy.
---
Final Thoughts
While iADT offers significant QoL benefits, its suitability depends on the disease's aggressiveness, patient priorities, and careful monitoring. For a 50-year-old with potentially aggressive prostate cancer, a cautious approach might involve starting with cADT to establish disease control, followed by a well-monitored trial of iADT. Collaboration with an experienced oncology team and adherence to evidence-based protocols like the A-DREAM study parameters will be crucial for success.
The likelihood of a 50-year-old with aggressive, widespread metastatic prostate cancer in the bones and lymph nodes surviving 5 years on intermittent androgen deprivation therapy (iADT) is influenced by several factors. These include the cancer's aggressiveness, response to initial therapy, overall health, comorbidities, and access to advanced treatments.
Factors Affecting Survival
1. Cancer Stage and Extent
Widespread metastases (both bone and lymph nodes) indicate advanced-stage cancer (Stage IV).
Bone metastases typically signal poor prognosis, and the presence of lymph node involvement worsens outcomes further.
2. Aggressiveness
Aggressive cancers (e.g., high Gleason score 8–10) are less likely to respond to treatment for long durations.
Younger patients often have more aggressive disease, which may progress more quickly during off-treatment phases of iADT.
3. Therapeutic Goals
ADT, whether continuous or intermittent, is palliative in this context. Its primary purpose is to manage symptoms, slow disease progression, and prolong survival, not cure the cancer.
4. Response to ADT
Patients who achieve a rapid and durable drop in PSA levels after starting ADT generally have better outcomes. However, PSA doubling time during off-treatment phases is a critical factor in iADT’s success.
5. Advanced Therapies
Survival can be prolonged if additional treatments such as next-generation androgen receptor inhibitors (e.g., enzalutamide or abiraterone), radiopharmaceuticals (e.g., radium-223), or chemotherapy (e.g., docetaxel) are incorporated.
---
Survival Data for Advanced Prostate Cancer
1. Continuous ADT
Studies show a median overall survival (OS) of 2-4 years for widespread metastatic prostate cancer with continuous ADT alone, especially for patients with high-volume disease. However, younger patients often tolerate additional treatments better, potentially extending survival.
2. Intermittent ADT
iADT is associated with comparable OS to cADT in low-volume metastatic or biochemical recurrence cases, but its effectiveness in high-volume, aggressive cancers is less clear.
SWOG 9346 Study: In patients with metastatic disease, intermittent ADT achieved a median OS of 5.1 years versus 5.8 years for continuous ADT. However, this slight difference was not statistically significant. Subgroup analysis suggested that high-risk patients might benefit more from cADT.
3. Younger Patients with Aggressive Disease
For a younger patient with aggressive, high-volume metastatic disease, iADT might result in shorter survival due to the potential for tumor progression during off-treatment phases.
For widespread metastases, 5-year survival rates are typically 15-30% with continuous treatment. iADT may reduce this percentage slightly, especially if treatment pauses allow tumor regrowth.
---
Estimating 5-Year Survival with iADT
Based on available data, the estimated likelihood of 5-year survival for this patient on iADT is approximately 20-25%, assuming:
He has access to advanced imaging and monitoring.
He responds well to initial ADT (e.g., rapid and sustained PSA decline).
He receives supplemental therapies like radiopharmaceuticals, androgen receptor inhibitors, or chemotherapy as needed.
If iADT is poorly managed (e.g., long off-treatment phases, insufficient monitoring), survival could drop below 20%.
---
Improving Survival Likelihood
1. Combination Therapies
Adding newer therapies like darolutamide, enzalutamide, or abiraterone to ADT may improve outcomes.
Combining with chemotherapy (e.g., docetaxel) has shown survival benefits in high-volume metastatic cases.
2. Monitoring
Close monitoring with PSA every 2-3 months and advanced imaging (e.g., PSMA-PET) is essential to detect early progression during off-treatment phases.
3. Bone-Targeted Therapies
Bisphosphonates (e.g., zoledronic acid) or RANKL inhibitors (e.g., denosumab) can help manage bone metastases and reduce skeletal-related events.
4. Clinical Trials
Enrollment in clinical trials exploring novel therapies could provide access to cutting-edge treatments.
5. Lifestyle Adjustments
Regular exercise, a balanced diet, and management of side effects (e.g., bone health) can support overall resilience.
---
Conclusion
For a 50-year-old with widespread metastatic prostate cancer, survival beyond 5 years on intermittent ADT alone is unlikely, particularly with aggressive disease. However, integrating advanced therapies and careful monitoring could improve survival chances. Continuous ADT, or a hybrid approach (starting with cADT and transitioning to iADT), might provide better control for such aggressive cancer. Ultimately, treatment should be individualized, balancing survival goals with quality of life.
With all due respect to our new robot overlords, I'm not sure why ChatGPT would go and assess my chances of survival under the circumstances at only 20-25%. Even under the poorly-managed parameters of the SWOG9346 trial (waiting until a PSA >20 to restart ADT, madness), median survival in their intermittent group was 5.1 years. Automatically assigning me to the low end of the survival bell curve when I'm following A-DREAM parameters is a leap.
Here's another problematic excerpt:
"A-DREAM Study: This trial focused on iADT as a viable alternative to cADT, showing that intermittent therapy could maintain oncological control while offering better QoL. Patients with non-metastatic or low-volume metastatic prostate cancer particularly benefited."
A-DREAM finished recruiting and launched in May of 2024, and there has been NO data published and available from it to date. Yet ChatGPT is describing the study in the past tense and how certain patient groups benefitted! ChatGPT is clearly talking out of its ass here and making stuff up!!!
Yes, the correlation between young age and aggressive prostate cancer presents challenges in managing the disease and tailoring treatment strategies. While prostate cancer is often slow-growing in older men, younger patients (e.g., those diagnosed under 55 or 60) are more likely to have biologically aggressive disease. Here’s why this correlation is a potential issue and how it impacts decision-making:
---
Why Is Cancer More Aggressive in Younger Men?
1. Tumor Biology
Younger men often present with higher-grade cancers (e.g., Gleason 8-10), rapid PSA doubling times, and higher tumor burden.
Their cancers are more likely to exhibit molecular characteristics associated with poor outcomes, such as alterations in BRCA1/2, PTEN, or other tumor suppressor genes.
2. Hormonal Environment
Younger men typically have higher baseline testosterone levels, which can drive prostate cancer progression.
Testosterone suppression through ADT may therefore play an even more critical role in controlling aggressive disease in younger patients.
3. Underdiagnosis and Late Detection
Prostate cancer in younger men is less common, leading to fewer screenings and later-stage diagnosis, often with metastases already present.
4. Disease Presentation
Younger men often have higher-volume disease, including multiple bone and lymph node metastases, as was seen in your case.
---
Challenges of Managing Aggressive Cancer in Younger Men
1. Balancing Aggressive Treatment with Long-Term Side Effects
Aggressive cancers often require intensive treatment (e.g., early chemotherapy, continuous ADT, or combination therapies).
Younger patients may face decades of side effects from treatment, including fatigue, cardiovascular risks, bone loss, and cognitive changes.
2. Impact on Quality of Life
Long-term ADT causes significant side effects, such as sexual dysfunction, decreased energy, and metabolic syndrome, which can have a profound impact on younger patients' active lifestyles and psychological well-being.
3. Potential Resistance to Therapy
Aggressive cancers are more likely to develop resistance to ADT and progress to castration-resistant prostate cancer (CRPC). This necessitates vigilant monitoring and may limit the duration of intermittent ADT's effectiveness.
---
Is the Correlation a Problem for Treatment?
1. Risk of Disease Progression
Aggressive cancers in younger men may progress more rapidly during the off-treatment phases of iADT.
Even with close monitoring, these cancers may outpace the response to resumed therapy, potentially leading to worsened outcomes.
2. Survival Trade-Offs
While intermittent ADT improves quality of life, it carries a small risk of reduced survival, especially in men with high-risk features. For younger men aiming for long-term survival, continuous ADT is often preferred to maintain tighter disease control.
3. Limited Evidence in Young Populations
Most clinical trials on iADT have involved older men with less aggressive cancers. Younger men with aggressive disease are underrepresented, making it unclear if the benefits of iADT (e.g., improved QoL without compromising survival) are equally applicable.
4. Long-Term Toxicity vs. Aggressive Disease Control
Younger men have more years ahead to experience the cumulative side effects of cADT. However, aggressive disease often necessitates prioritizing disease control over quality of life, at least in the early stages of treatment.
---
Potential Solutions to Mitigate Challenges
1. Personalized Monitoring During iADT
Younger men may benefit from more frequent PSA tests (e.g., every 4-6 weeks) and imaging to detect early progression during off-treatment phases.
Stricter PSA thresholds for resuming ADT (e.g., PSA >4 rather than >10-20) may help catch progression earlier.
2. Combination Therapies
Adding novel agents like darolutamide (Nubeqa) or enzalutamide to ADT may improve disease control while allowing intermittent therapy.
Younger patients might benefit from using these therapies to maintain efficacy during iADT off-phases.
3. Bone Health and Cardiovascular Monitoring
For younger patients on cADT, proactive measures like bisphosphonates, exercise programs, and cardiovascular risk management can mitigate long-term side effects.
4. Clinical Trial Participation
Younger men with aggressive disease should be encouraged to participate in trials like A-DREAM to provide more data on how iADT or other novel strategies work for this specific population.
---
Conclusion
The correlation between young age and aggressive prostate cancer does complicate treatment decisions. While iADT offers clear QoL benefits, its suitability for younger men with aggressive cancers remains uncertain due to the potential risk of progression during off-treatment phases. For such patients, continuous ADT, at least in the initial years of treatment, might offer a better balance of disease control and survival. That said, with proper monitoring and personalized adjustments, iADT can still be a viable option for younger patients who prioritize quality of life.
Prolonged time without androgen suppression during cancer treatment can accelerate resistance mechanisms for several reasons. The underlying biology of prostate cancer cells and how they adapt to hormonal changes plays a key role. Here’s why this happens:
---
1. Selection of Resistant Cancer Cell Clones
Prostate cancers are often heterogeneous, meaning they consist of different types of cells, including:
Androgen-dependent cells: Require androgens (testosterone and dihydrotestosterone) to grow.
Androgen-independent cells: Can grow with little or no androgen stimulation.
During androgen suppression (e.g., with ADT), androgen-dependent cells are suppressed or die, while androgen-independent cells might survive or grow more slowly.
When androgens return (as in the off-treatment phase of intermittent ADT or stopping therapy altogether), androgen-dependent cells may regrow.
This regrowth creates competition between androgen-dependent and androgen-independent cells.
Over time, selection pressure can favor the growth of androgen-independent or castration-resistant prostate cancer (CRPC) clones.
---
2. Adaptation of Androgen Receptors (AR)
Prostate cancer cells adapt to fluctuating androgen levels by upregulating androgen receptors (AR) or altering AR function.
Mechanisms include:
AR overexpression: More receptors make cancer cells hypersensitive to even low androgen levels.
AR mutations: Allow the receptor to be activated by other hormones or even anti-androgens (e.g., enzalutamide).
Constitutively active AR: Mutant ARs that are always “on” even without androgens.
Periods of androgen recovery can drive further adaptation, as the cancer cells “learn” to survive and grow in both low-androgen and high-androgen environments.
---
3. Increased Tumor Heterogeneity
Fluctuating androgen levels (on-and-off treatment) can create a more diverse population of cancer cells within the tumor.
Heterogeneous tumors are harder to treat because some subpopulations may inherently resist therapies.
---
4. Tumor Microenvironment Changes
Androgens affect not only cancer cells but also the surrounding tumor microenvironment.
Androgen recovery can promote processes such as:
Angiogenesis: Growth of new blood vessels to supply the tumor.
Immune evasion: Changes in the immune response that allow cancer cells to escape detection.
These changes may facilitate cancer progression and resistance.
---
5. Androgen-Independent Pathways
Over time, prostate cancer cells may activate alternative growth pathways that don’t depend on androgens.
Examples include:
Upregulation of signaling pathways like PI3K/AKT or MAPK.
Use of neuroendocrine differentiation, where cancer cells shift toward a different, more aggressive phenotype.
Periods without androgen suppression may give these pathways time to develop further, reducing the effectiveness of ADT when it is reintroduced.
---
6. Prolonged Time for Disease Progression
During off-treatment periods, the return of testosterone allows androgen-sensitive cancer cells to regrow, potentially increasing the overall tumor burden.
A larger tumor burden means a greater chance of resistance mechanisms emerging.
---
Evidence from Clinical Studies
While intermittent ADT (iADT) has been shown to be effective in some settings, it requires strict monitoring and timely reintroduction of therapy. Delays in resuming ADT (e.g., waiting until PSA >20 ng/mL in SWOG 9346) may increase the risk of resistance.
In trials like EORTC 30985 and PR7, strict PSA thresholds for restarting ADT helped maintain outcomes comparable to continuous ADT (cADT), but prolonged untreated periods are risky, especially in high-burden or aggressive cancers.
---
Key Takeaway
Prolonged time without androgen suppression creates an environment where prostate cancer cells can adapt, evolve, and develop mechanisms to survive future treatments. This is why careful monitoring and strict thresholds for reintroducing ADT are critical in intermittent ADT protocols. In cases of aggressive or high-volume metastatic disease, continuous ADT may be safer to prevent the emergence of resistance.
My first medical oncologist professor Richard Epstein wanted to put me on intermittent ADT without an early docetaxel chemotherapy but my first radiation oncologist recommended with the board of urologists of my hospital early docetaxel chemotherapy and a continuous ADT. My radiation oncologist said that if I want to benefit of the radiation treatments in the future I should stay on the continuous ADT.
I've had this same kind of discussion. I am 74. I was diagnosed with Gleason 8 eight years ago and treated. Prostate was not removed. I have not been on ADT since my first six month injection 8 years ago. My PSA has crept up in the last year or two but only to 3.2. Axumin and Pylarify scans, as well as a prostate MRI, all came back clear. My urologist insisted on prescribing finasteride. That caused terrible dental sensitivity problems so I discontinued it. With some trepidation I agreed to taking dutasteride. He would not agree to intermittent use. Seems like the only thing dutasteride did was halve the PSA readings while on it. He then left the practice for greener / cooler pastures (I am in the Phoenix area). My new urologist has agreed to let me experiment with intermittent use or quit the dutasteride altogether if my PSA behaves. It will continue to be checked every four months now. I've asked about BAT years ago but that was always a solid no. I don't see how a PSA reading below 4 at my age would require any prescription. Besides, I am gynecomastia prone. Good luck with your treatments. It wasn't fair getting this disease at your young age.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Consulting on next steps
PSA suppression
3rd & 4th pBAT cycle results with daro question