In my researching into Provenge (both the treatment itself and where to receive it), and in reviewing posts on PCa forums (perhaps mostly other forums besides this one), I've noticed some interesting patterns.
Provenge was approved around 2010 and had a troubled opening. The small company, after long FDA trials, had little money to market it well, had trouble getting quick Medicare and insurance carrier approval, other drugs that promised good results (alternatives to using Provenge, but not direct competitors as immunotherapy) that were cheaper or secured coverage quickly. So Provenge ground somewhat to a half, but seemingly has (slowly) gotten a second life during the last 10 years.
Many clinics and large institutions, including apparently many "centers of excellence," do but use it as all. Places that do use it, of course, recommend it, explain it, etc.
But those places that don't offer also don't seem to mention (much less recommend) it to patients. Some even seem to badmouth it, saying the original FDA clinical trials were flawed and effectively useless. Some even say that one large center profits from it and recommends it for that reason (I think they mean UCLA). The clinical trial criticism has been around for years and popped up when the company sought European approval, which it got (I don't think it's done well there, though). Supporters and detractors on both sides.
All this is notable because I've long suspected that economic and other interests drive clinical recommendations, even to the various hormone meds. When I was first diagnosed in 2018, my urologist was going to put me on Firmagan. I left him to see an oncologist. I saw several at different clinics, none of which used Firmagan, including the one I've been using for over six years. Over the years, I've asked the various nurses who give the Lupron shots and none are familiar with Firmagan. At other clinics the situation may be the reverse.
I suspect this affects sequencing of treatments, use of various types of radiation, whether to double up or triple up on treatments (or stick to the "wait till this one fails" strategy), etc.
Anyone else notice this phenomenon?
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I know there will be people who will call me a conspiracy theorist but it is worse than that. The economics of profit (I am a capitalist) come into play when they have costs to recoup and longer term treatments mean a more recurring revenue stream. Also, the funding of research is often from governments which would have a significant problem funding Social Security and pensions if life expectancies skyrocketed. Doubt this? Explain why almost no research goes to stem-like sensescent cells that are the real reason why treatments are always palliative when cancer is metastatic. That is not to say that the researchers themselves don’t want to do the right thing, they just don’t get the funding.
Interesting comments on the politics of pharmaceuticals.
With respect to Provenge my understanding is that (in UK) it was decided that poor cost effectiveness stopped it being approved by NHS. The effect on survival was small.
However the wider issue is the extent to which industry and academic vested interests drive the development of androgen blockading drugs to the detriment of other possible new therapeutic models. Ca prostate is a common condition and the newer androgen focussed drugs are expensive and profitable. Inevitably the profits drive both pharm and academic goals, and the design of clinical trials. This is understandable but inhibits research into other imaginative approaches like Provenge.
I have noticed that if one looks closely at the data , for example on enzalutamide, the net benefits to men over 75 are marginal if any. Yet protocols do not reflect the balance of risk-benefit at different ages (chronological and biological) and discussion about this with the treating clinicians in my experience is largely absent. Why? Because the interests of all involved, except the patient, are too closely aligned.
I have also become cynical about Standard of Care because it seems that too rarely is this interpreted and applied in the light of the individual patients needs and clinical circumstances.
Anyway, sorry to ramble, what does my opinion matter? I just think it pays to be sceptical when you are offered the next latest treatment.
No problem, I appreciate your comments. I acknowledge that at this point I don't know what Provenge did, but FDA approval was good enough for me given full coverage on costs and minor side effects, and ability to do all other treatments afterwards.
There was a much more recent (2020) small trial where Provenge was compared to abiraterone acetate and possibly enzalutamide. Provenge showed greater efficacy than either. I haven't studied it scientifically, a little beyond me, but see what you think.
The trial you're referencing is likely the **ASCENT trial** (2018-2020), a phase 2 study investigating the sequencing of **sipuleucel-T (Provenge)** followed by androgen receptor-targeted therapies (ARTs) like abiraterone acetate or enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC). Here's a breakdown of the findings and context:
### Key Results:
1. **Time to PSA Progression**:
- Patients who received sipuleucel-T **before** ARTs (abiraterone/enzalutamide) had a **median time to PSA progression of 10.3 months** vs. **4.3 months** in the control group (ARTs alone).
- This suggests a potential benefit to *sequencing* immunotherapy before hormonal therapy.
2. **Immune Activation**:
- The sipuleucel-T group showed increased immune cell activation (e.g., antigen-presenting cells, T-cells), which may prime the immune system to enhance subsequent ART efficacy.
3. **Overall Survival (OS)**:
- OS data were immature but trended favorably for the sipuleucel-T group (median OS not reached vs. 30.6 months for controls).
### Why This Doesn’t Prove Provenge is "More Effective":
- **Trial Design**: This was a **small phase 2 study** (n=94) focused on *sequencing*, not head-to-head comparison. The control group received ARTs alone, while the experimental group received Provenge followed by ARTs. The benefit may stem from combination effects rather than Provenge superiority.
- **Endpoints**: Provenge’s strength is improving overall survival (OS) with delayed effects, while ARTs more rapidly reduce PSA and delay progression. Cross-trial comparisons are problematic due to differing patient populations and endpoints.
- **Clinical Context**: ARTs remain first-line for mCRPC due to faster responses and ease of use. Provenge is typically reserved for asymptomatic/minimally symptomatic patients due to its delayed action.
### Limitations:
- Small sample size and lack of statistical power for OS.
- Potential selection bias (patients with slower disease progression may have been enrolled).
- No direct comparison of Provenge vs. ARTs alone; the trial tested a *treatment sequence*.
### Bottom Line:
The ASCENT trial suggests **sequencing sipuleucel-T before ARTs may improve outcomes** in mCRPC, possibly due to immune priming. However, this does not mean Provenge is inherently more efficacious than abiraterone or enzalutamide. Larger phase 3 trials are needed to confirm these findings and define optimal treatment sequences.
For clinical practice, ARTs remain standard first-line, while Provenge is considered for select patients. The trial highlights the potential of immunotherapy combinations but doesn’t overturn current guidelines. Always consult recent literature for updates, as this field evolves rapidly.
Take a look at this. Not the Ascent trial, but more of a retrospective study. If nothing else, it shows that Provenge is provoking more interest during its second life.
I believe in provenge and I would be happy to try it. My MO things that because it doesn't lower PSA it is maybe not effective, but I believe (I am not a doctor only my personal opinion) that maybe it stops the cancer stem cells spreading. It is proven that it extends survival and lots of people experienced that. Therefore it must be controlling the prostate cancer stem cells. Only my opinion. I would gladly take it.
The real-world study you’ve shared offers intriguing insights into **sipuleucel-T (Provenge)** compared to androgen receptor pathway inhibitors (ARPIs) like abiraterone or enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). Here’s a structured breakdown of the findings, context, and key considerations:
---
### **Key Findings from the Real-World Analysis**
1. **Survival Benefit**:
- Patients receiving sipuleucel-T **at any line of therapy** had a **median OS of 35.2 months** vs. **20.7 months** for ARPI-only patients (HR 0.59, 41% reduced death risk).
- In **first-line use**, sipuleucel-T showed a **median OS of 34.9 months** vs. **21.0 months** for ARPIs (HR 0.56, 44% risk reduction).
2. **Healthcare Utilization**:
- Fewer emergency department (ED) visits for sipuleucel-T (164.3/100 patients/year) vs. enzalutamide (194.5) or abiraterone (206.4).
3. **Study Design**:
- Retrospective analysis of Medicare claims (2013–2017; 6,044 patients).
- Compared sipuleucel-T (used at any line or first-line) vs. ARPIs, adjusting for confounders with statistical methods like inverse probability of treatment weighting (IPTW).
---
### **Why This Seems Compelling But Requires Caution**
1. **Real-World vs. Clinical Trials**:
- **Strength**: Reflects "real-life" practice with diverse patients (e.g., older, comorbidities).
- **Limitations**:
- **Selection Bias**: Sipuleucel-T is typically given to asymptomatic/minimally symptomatic patients, who may inherently have better prognoses.
- **Confounding**: Unmeasured factors (e.g., disease aggressiveness, access to care) could skew results, despite statistical adjustments.
- **Survival Inflation**: The ARPI group’s median OS (20.7 months) is shorter than in pivotal ARPI trials (e.g., COU-AA-302: abiraterone OS ~34.7 months), raising questions about patient comparability.
2. **Conflict of Interest**:
- The study was funded by Dendreon (sipuleucel-T’s manufacturer), and its CMO endorsed the results. While not invalidating the data, this underscores the need for independent validation.
3. **Line of Therapy**:
- Only **10.8%** received sipuleucel-T first-line, vs. **55.9%** for abiraterone. Sipuleucel-T’s benefit may reflect its use in selected patients or synergistic effects with subsequent therapies (e.g., ARPIs, taxanes).
---
### **Contextualizing with Prior Evidence**
1. **Sipuleucel-T’s Historical Role**:
- Approved based on the **IMPACT trial** (2010), showing a **4.1-month OS benefit** vs. placebo in asymptomatic/minimally symptomatic mCRPC.
- ARPIs (abiraterone/enzalutamide) later demonstrated larger OS gains in symptomatic patients, becoming first-line standards due to rapid PSA responses and ease of use.
2. **ASCENT Trial vs. This Study**:
- **ASCENT** (phase 2) suggested *sequencing* sipuleucel-T before ARPIs improves outcomes, possibly due to immune priming.
- This real-world analysis implies sipuleucel-T’s benefit even when used *at any line*, but doesn’t clarify optimal timing or isolate its effect from combination therapy.
---
### **Why ARPIs Remain First-Line in Guidelines**
1. **Hierarchy of Evidence**:
- ARPIs have robust phase 3 RCT data supporting their efficacy. Real-world studies (like this one) are hypothesis-generating but less definitive.
2. **Practical Considerations**:
- Sipuleucel-T requires leukapheresis and is logistically complex. ARPIs are oral and work faster, making them preferable for symptomatic patients.
3. **Patient Selection**:
- Sipuleucel-T’s benefit may be greatest in early, less aggressive disease—a population underrepresented in this Medicare cohort (median age 75–78).
---
### **Takeaways for Clinical Practice**
- **Sipuleucel-T’s Niche**: Likely benefits select asymptomatic patients, especially when sequenced with ARPIs or other therapies.
- **Combination Potential**: Immunotherapy (e.g., sipuleucel-T) + ARPIs may synergize, but optimal protocols require phase 3 trials.
- **Real-World Caveats**: While encouraging, this analysis shouldn’t override RCT-driven guidelines. However, it supports considering sipuleucel-T earlier in treatment sequences for eligible patients.
---
### **Bottom Line**
This study adds to evidence that sipuleucel-T may extend survival in mCRPC, particularly when integrated into treatment pathways. However, ARPIs remain first-line due to stronger trial data and practicality. The findings highlight the importance of **personalized sequencing** and the potential role of immunotherapy in prostate cancer—a field evolving with new agents (e.g., PARP inhibitors, PSMA-targeted therapies). Always weigh patient-specific factors (symptoms, comorbidities) and stay updated on emerging trials.
Your breakdown is both comprehensive and balanced. It accurately highlights the promising survival benefits associated with sipuleucel-T while also emphasizing the inherent limitations of real-world retrospective analyses. A few points stand out:
Strengths:
You clearly articulate the survival advantages seen with sipuleucel-T, including its performance as a first-line therapy.
The discussion on reduced emergency department visits provides an important perspective on healthcare utilization and patient quality of life.
Limitations & Caution:
You rightly note potential biases such as selection bias and confounding—key concerns in retrospective Medicare claims analyses.
The discrepancy between the observed median OS in the ARPI group versus that reported in pivotal trials raises valid questions regarding patient comparability.
Funding sources and potential conflicts of interest are appropriately flagged, reminding clinicians and researchers to seek independent validation.
Contextual Integration:
By comparing these findings with the historical IMPACT trial data and noting the practical challenges of sipuleucel-T administration, your analysis situates the real-world data within the broader treatment landscape for mCRPC.
Highlighting the potential benefits of sequencing or combining sipuleucel-T with ARPIs further underscores the evolving nature of treatment strategies in this field.
Clinical Implications:
The takeaway—that sipuleucel-T may have a role, particularly in carefully selected patients and in a complementary sequence with other therapies—is well stated.
Your reminder that ARPIs remain first-line due to robust RCT data and practical considerations is a crucial point for guiding clinical decisions.
Overall, your analysis captures the nuanced interplay between real-world evidence and controlled trial data, emphasizing that while the findings are intriguing, they should be integrated into clinical practice with careful patient selection and an understanding of their limitations. This balanced view is essential for advancing treatment strategies in mCRPC while awaiting further prospective studies.
I'm not sure I understand your question. What study? The clinical trial I'm in?
Ideally, on today's SOC, Provenge is begun just after castrate resistance sets in on a metastatic patient, preferable while PSA is still very low and before the patient has ever done chemo.
The patient continues the ADT or ADT/ARPI all through and onward. Hormone therapies do not conflict with Provenge. There are studies underway, I understand, to begin Provenge before castrate resistance or to combine it with certain things, like BAT. But those are clinical trials other than the one I'm on.
If that didn't answer your questions, let me know.
The article I published compared use of Provenge without ARPI vs ARPI without Provenge. Patients could have any other treatments at any point in time. Retrospective studies, not a head-to-head comparison.
In Seasid's lengthy posts above, he did a deep dive through AI on other clinical trials involving Provenge and ARPIs. Very lengthy, but well worth reading.
Actually, this particular comment by Seaside reviews in detail the study in the article I posted (strengths and limitations), along with a comparison to certain trials involving Provenge.
please review my previous posts on Provenge. Including todays. As a follow up, i did a deep dive into the clinical trial results of Provenge. One of the reasons it gets badmouthed is that its own study showed only a four month median survival benefit. However my deeper dive, showed an interesting result when the results were broken down by initial PSA at initiation of treatment. It turns out that the lower your starting PSA, the longer the benefit with the lowest group (under 20…going by memory now) experiencing a 14 month survival benefit. Keep in mind, they were comparing these low starting PSA men to other men on a placebo that were also starting with a low PSA. That’s 350% better than the overall results compared to thhe overall trial. . This led my oncologist and me to the conclusion that Provenge could be much more effective on hormone sensitive men with PSAs under 10. When I inquired with some people I thought to be in the know, as to why Provenge was never tested on hormone sensitive men, the answer made some sense. With luke warm reception in the medical community, their resources were limited for another trial. More importantly, hormone sensitive men were now living so long that doing a trial to a conclusion of ‘median survival’ would simply take too long and be too expensive.
Regarding the 4-month life extension, isn't that about what abiraterone and docetaxel showed-mean value? Been a while since I studied that.
I did use Provenge when my PSA was low but increasing--still under 2. Two weeks after finishing, my PSA was 2.72, all-time high. However, that is now reversing following radiation. PSA on 3/14/2025 was .39, an all-time low since beginning treatment in Fall 2018. Hope it continues, or at least holds.
Good question. I think since my PSA had risen from .67 at end of 2022 to 1.9 by August 2024, I was considered castrate resistant. With rising but still very low PSA, seemed like ideal time to use.
Interesting insights. During my initial discussions with my first MO, a research scientist at Moffitt Cancer Center in Tampa, FL, he laid out what he thought (based on his knowledge in 2014) would be the best course of action. That included Provenge after Xtandi failed to keep my PSA below 2.0. His reasoning was that, from what he saw, those who took Provenge had a better QOL and perhaps lived longer.
When I moved to Rochester, NY, my MO at the Wilmont Cancer Center at the University of Rochester Medical Center, didn't think it would be helpful. But since I asked for it and was willing to jump through the hoops necessary to get it, he approved it.
URMC makes it difficult to get Provenge because their immunology department will not do the leukapheresis to extract the T cells, because it would be "a conflict of interest." So I had to travel an hour away to get that done at a Red Cross Center. URMC did the infusion a few days later in their infusion center, though.
I thought it very interesting that a university medical center with a dedicated cancer center would place road blocks in the way of a treatment. If renewed interest in Provenge proves that those who have had it live longer with the disease, do you think they may change their mind? Food for thought.
I also had to travel 70 miles one way to a large One blood facility to get my leukapheresis done. Then the re-infusion was done at the urology clinic here in Daytona. The drug manufacturer kindly provided a free ride to the One blood facility each time, which was nice.
Yes, if it shows increased lifespan, it will get more notice, but slowly! My oncology clinic still doesn't use the doublet therapy for existing metastatic patients, unless the patient requests it.
In the context of metastatic prostate cancer, the statement reflects a clinic's approach to treatment that may not fully align with current evidence-based guidelines. Here's a breakdown:
### 1. **What is "doublet therapy"?**
- In metastatic **hormone-sensitive prostate cancer** (mHSPC), doublet therapy typically combines **androgen deprivation therapy (ADT)**—the standard first-line treatment—with either:
- **Chemotherapy** (docetaxel), or
- A **novel hormonal agent** (e.g., abiraterone, enzalutamide, apalutamide, or darolutamide).
- Landmark trials (e.g., CHAARTED, STAMPEDE, LATITUDE) show that adding these agents to ADT improves survival compared to ADT alone. Most guidelines now recommend doublet therapy as the **standard of care** for eligible patients.
---
### 2. **Why might the clinic avoid doublet therapy?**
Possible reasons for not adopting it as standard:
- **Outdated practices**: The clinic may not have updated protocols to reflect newer evidence (some trials are recent, e.g., 2015–2018).
- **Patient factors**: Concerns about toxicity (e.g., chemotherapy side effects) in frail or older patients.
- **Resource limitations**: Cost or lack of access to newer drugs (e.g., abiraterone can be expensive).
- **Clinical judgment**: Some providers may still debate which patients benefit most (e.g., high-volume vs. low-volume disease).
---
### 3. **"Unless the patient requests it"**
- This highlights **shared decision-making**. While the clinic may not proactively offer doublet therapy, they are open to it if:
- The patient is informed about the benefits/risks (e.g., improved survival vs. side effects).
- The patient advocates for a more aggressive approach, possibly after researching guidelines or seeking a second opinion.
- It also implies the clinic may prioritize patient autonomy but lacks a standardized protocol for offering these therapies upfront.
---
### 4. **Key Takeaway**
Current guidelines (NCCN, ESMO, ASCO) strongly recommend doublet therapy for most mHSPC patients. A clinic avoiding this approach unless prompted by the patient might be lagging behind modern standards. Patients or families seeking optimal care may need to advocate for guideline-aligned treatments or seek a second opinion.
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Reaching the final destiny on my life's journey
68 Ga-PSMA scans available in USA?
Does a prostate cancer treatment flowchart exist. 
When is enough enough?
