Hypermetabolic node with partial necrosis.

[Shellhale]

Husband's PSMA scan on 3/26/25 showed 1 new enlarged hypermetabolic lymph node on the right common illiac 3.6 cm x 3.6 cm with partial necrosis. SUV max 6.2. Increased metabolic activity of previous metabolic right external illiac lymph node which now measures maximum SUV of 6.9. Previously 2.9. The third lymph node in the left common iliac is similar in size and activity to prior measuring 7mm long axis with max SUV 3.2.The prostate was only radiated and showing no lesions now with a max SUV of 1.0. Completed 8/16/2024.

Our appointment is on Wednesday with MO and we have an appointment with a RO specializing in SBRT on 4/21.

He has G9, last FoundationOne somatic testing showed PTEN, TP53 and TMPRSS2-EPR fusion on 9/2023. Already asked MO for more tumor DNA sequencing for next appointment .

Looking for information on anyone who has treated or any experience in partial necrosis tumors. This is a new finding and I am very concerned. PSA is still .90 He does not tolerate docetaxel. 1 round completed 11/2023. He Is on monotherapy nubeqa. Just added Orgovyx for 8 days now. But really does not want to continue it. I am trying to convince him to do it intermittently for now. I am preparing for his appointment with MO on Wednesday looking for systemic treatment options. Also looking at clinical trials.

More info in Bio. He was restaged Oligometastic T3, N1, M1.

[Tall_Allen]

Hopefully, salvage radiation to the entire pelvic lymph node area (up through the common iliac lymph nodes) can get the rest.

BTW- your radiologist is lazy. PSMA-expressing lymph nodes are not "hypermetabolic." That is terminology that applies to FDG PETs, which is commonly used for other cancers.

[Shellhale in reply to Tall_Allen]

What does that term really mean "hypermetabolic"? And do you know if necrotic tumors are treated differently? I am assuming it's aggressive or it's necrotic from prior treatments? Thanks for your response.

[Tall_Allen in reply to Shellhale]

Necrosis of cancer tumors is a good thing!

Hypermetabolic on an FDG PET scan refers to cancer cells of other kinds of cancer that have increased metabolism of glucose. The radiologist was just lazy in using that terminology from other cancers he more typically investigates. It doesn't really matter.

[Shellhale]

Oh i see. Well, that is a relief than regarding the necrosis. Hopefully the MO will have suggestions for systemic treatments other than ADT.

[Seasid]

**Key Considerations for Clinical Trials and ADT Requirements:**

While **many clinical trials** (especially in advanced/metastatic settings) **do require continuous ADT** as part of standard therapy, **exceptions exist** depending on the trial’s design, disease stage, and treatment goals. Below is a breakdown of scenarios where ADT may not be mandatory:

---

### **1. Trials Allowing Intermittent ADT or ADT-Free Periods**

- **Oligometastatic Trials** (e.g., STOMP, ORIOLE):

Some studies combine metastasis-directed therapy (e.g., SBRT) with **intermittent ADT** to test whether local treatment can delay systemic progression and reduce ADT exposure.

- Example: The [ORIOLE trial](clinicaltrials.gov/ct2/show... allowed intermittent ADT in select patients.

- **De-Escalation Trials**:

Emerging studies aim to minimize ADT use (e.g., [NCT03795207](clinicaltrials.gov/ct2/show... in favorable-risk patients or those with exceptional responses to treatment.

---

### **2. Trials in Castration-Resistant Prostate Cancer (CRPC)**

Trials for **CRPC** (where cancer progresses despite castrate testosterone levels) often **do not require ongoing ADT** if the patient is already castration-resistant. Examples include:

- **PARP Inhibitor Trials** (e.g., PROfound, TRITON3):

For patients with HRR mutations, these trials may not mandate ADT if the patient is already on stable androgen blockade.

- **Immunotherapy/Bispecific Antibody Trials** (e.g., AMG 509, pembrolizumab):

Often tested in CRPC without requiring concurrent ADT.

---

### **3. ADT-Free Trials in Early-Stage Disease**

- **Active Surveillance Trials** (e.g., NCT04002219):

For low-risk localized disease, trials may avoid ADT entirely.

- **Focal Therapy Trials**:

Studies testing HIFU or cryotherapy in localized disease often exclude ADT.

---

### **4. Trials Targeting Non-AR Pathways**

Trials testing agents that bypass androgen receptor (AR) signaling may allow ADT pauses if they focus on:

- **PTEN/TP53-Targeted Therapies**:

Trials with AKT inhibitors (e.g., ipatasertib) or CDK4/6 inhibitors.

- **Immunotherapy Combinations**:

Trials combining checkpoint inhibitors with other modalities (e.g., NCT03835533).

---

### **5. Practical Steps for Your Husband’s Case**

1. **Genomic Testing**:

Update tumor sequencing to identify actionable mutations (e.g., HRR, BRCA) for PARP inhibitor eligibility **without ADT dependence**.

2. **Trial Search Filters**:

Use [ClinicalTrials.gov](clinicaltrials.gov) with keywords:

- *“intermittent ADT”*

- *“ADT-free”*

- *“castration-resistant prostate cancer”*

- *“oligometastatic”*

3. **Consult MO/RO About These Options**:

- Ask specifically about trials for **oligometastatic disease** or **CRPC** that do not require continuous ADT.

- Highlight his intolerance to ADT and desire to minimize its use.

---

### **Examples of Relevant Trials (2024)**

1. **NCT05146973**: PSMA-targeted therapy in oligometastatic patients (may allow intermittent ADT).

2. **NCT05572373**: Testing SBRT + darolutamide in hormone-sensitive patients (may have ADT flexibility).

3. **NCT04720157**: Atezolizumab + PARP inhibitor in CRPC (no ADT required).

---

### **Critical Takeaway**

While **many trials do require ADT** (especially in hormone-sensitive disease), exceptions exist. Prioritize trials in **CRPC, oligometastatic, or biomarker-selected populations** where ADT may be optional. Advocate for genomic testing and work with his care team to filter trials by eligibility criteria that align with his preferences.

Let me know if you’d help refining a ClinicalTrials.gov search or interpreting specific trial protocols!

DeepSeek said

[Shellhale]

That was great. That gave a great place to start. The PTEN/TP53 targeted therapies would match his current genomic profile. However, I don't know if those mutations are still there since that tissue is sample is 18 months old. Definitely need more somatic testing. Also those last 3 trials I will look into as well. Thank you.

[j-o-h-n]

Note: The following is for dummies like me.

Partial necrosis in tumors refers to areas within a tumor where cells have died, but not the entire tumor, which can be a common finding in various cancers and is often associated with poorer outcomes.

Here's a more detailed explanation:

What is tumor necrosis?

Tumor necrosis, or necrosis, is the death of cells within a tumor, often occurring in areas where the tumor outgrows its blood supply, leading to oxygen and nutrient deprivation.

Partial necrosis vs. complete necrosis:

Partial necrosis means only some parts of the tumor are dead, while complete necrosis indicates the entire tumor is dead.

Why is it important?

Prognostic Implications: The presence of tumor necrosis, whether partial or complete, can be a poor prognostic factor, meaning it is often associated with poorer survival outcomes and higher rates of recurrence.

Treatment Response: Tumor necrosis can be an indicator of how well a tumor is responding to treatment, with complete necrosis after treatment suggesting a good response.

Mechanism of Necrosis: Tumor necrosis can be caused by a variety of factors, including metabolic stress, inflammation, and even the immune system's response to the tumor.

Tumor Necrosis Factor (TNF): TNF is a molecule that plays a role in inflammation and immune responses, and it can also contribute to tumor necrosis.

Examples:

Hepatocellular carcinoma (HCC): Partial necrosis is a common finding in HCC nodules, and its presence has been linked to tumor recurrence after liver transplantation.

Breast cancer: Infarct necrosis, a type of tumor necrosis, has been reported in breast cancer, though it is rare.

Ewing sarcoma: Complete tumor necrosis after neoadjuvant chemotherapy is a key indicator of a good response to treatment in patients with Ewing sarcoma.

Research and Future Directions:

Researchers are actively investigating the mechanisms underlying tumor necrosis and how it impacts tumor progression and treatment outcomes. Understanding these mechanisms is crucial for developing more effective therapies.

Good Luck, Good Health and Good Humor.

j-o-h-n