The 50% statement: MISUNDERSTOOD and MISINTERPRETED!
IF you have no time to read the full write up: Here is the gist of it!
In current practice (before 64Cu-SAR-bisPSMA), every patient with BCR and a negative SOC, has a 50% chance of being on the wrong treatment, and the doctor does not know which patient it is!
Let that sink! THE END!
THE JEWEL OF THE CROWN!
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The LONG write-up!
To really understand the meaning of a scientific result, you need to understand THREE things in particular; the objectives of the experiment (derived from the hypothesis being tested), the inclusion criteria, and the methodology. I exclude the background because that can be limitless – hence, impractical for most people. Results are situationally relevant, and their validity is related to the THREE things.
This survey referred to was part of the COBRA Trial: 64Cu-SAR-bisPSMA PET/CT in Biochemical Recurrence (BCR) of prostate cancer. Here is the full COBRA Protocol.pdf
The said data came from one of the Exploratory Study Objectives and Endpoints section;
- OBJECTIVE: To assess the impact of 64Cu-SAR-bisPSMA PET/CT on disease management.
- ENDPOINT: Proportion of participants with any change in intended PC treatment due to either the Day 0 or Day 1 scan.
To understand what CHANGE of intended treatment means - you need to understand what the treatment plans would actually have been that you are now changing from.
But lets start with a KEY DEFINITION of the condition coz that’s key (I know I'm repeating myself- BIOCHEMICAL RECURRENCE (BCR) is a rise in PSA (prostate-specific antigen) after initial treatment (surgery or radiation) for confirmed prostate cancer, with no clinical or radiographic evidence of metastasis.
- The cancer is 'back', but we can’t see it! It could be in the prostate bed (the area and tissue that surrounded the prostate before it was extracted via surgery if the patient had a prostatectomy, or it may have reached some lymph nodes (its metastasized).
Management options for BCR
⦁ Salvage Radiation Therapy to the prostate bed (40-50% of patients with BCR go this way)
⦁ Androgen Deprivation Therapy (30-40% of patients with BCR)
⦁ Observation (10-20%). PSA (level and kinetics) and patient age influence this choice.
So, this is what the doctors were going to do before they had the 64Cu-SAR-bisPSMA PET/CT.
COBRAINCLUSION CRITERIA (aspects key to the discussion):
a) BCR (as defined above)
b) Negative or equivocal findings for PC on conventional imaging performed as part of SOC workup within 60 days prior to Day 0
COBRA METHODOLOGY Refer to Table 5 (Schedule of Assessments)
On the Disease Management Form;
a) SCREENING: The doctor was asked to document planned treatment based on the results known PRIOR to a Clarity Cu64-Sar-bisPSMA scan. See Management above.
b) Day 7 SAFETY VISIT: Post Clarity Cu64-Sar-bisPSMA scan, and based on the results of this scan, the doctor was asked to document planned treatment – now that they have new information.
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RESULTS
"Following 64Cu-SAR-bisPSMA PET imaging, investigators indicated that they would change the treatment plan of approximately half of the patients (48%) ... Of these patients, two-thirds (67%) proceeded to receive systemic and/or focal therapy."
INTERPRETATION of this RESULT in particular!
FIRSTLY, back to the CONTEXT: a) Remember that ALL patients that were included here had previously completed Prostate cancer treatment and had been called “cancer free”, until their PSA levels started rising! So, they were suspected of having a recurrence, which SOC was unable to pinpoint!
b) Patients in this situation can be monitored if appropriate, or proceed to treatment, without any confirmation. Afterall, Doctors know that SOC misses over 50% of cancer lesions when they exist. The treatment may be one or both Salvage Radiation Therapy (to the area of most concern – the prostate bed) or Androgen Deprivation Therapy.
c) The Cu64-Sar-bisPSMA scan is experimental. Management of care follows SOC. But the doctors were still given the result of the Cu64-Sar-bisPSMA scan to decide what to do. But it’s still experimental, so its ok for doctors and patients to ignore it and continue with their plan.
d) Not all had a positive Cu64 scan! No point pursuing this as its not the question (its irrelevant).
Lets Group the patients with a positive Cu64 scan – by treatment intention!
GROUP A:Proceeding to Salvage Radiation Therapy (SRT)
(Per Ref documents including Clinical Guidelines at the bottom) SRT is most effective when PSA is ≤ 0.5 ng/mL, and patients are young, fit, and healthy. The plan here is to deliver External Beam Radiation Therapy (EBRT) to the prostate bed, based on the assumption that recurrence is local (even if imaging can't find it).
An experimental 64Cu-SAR-bisPSMA scan is done and detects lesions:
This can lead to:- A change of plan: For example, if the scan shows pelvic lymph node involvement, the treatment plan might expand to include whole pelvis radiation or adding ADT to SRT. In some cases, if widespread disease is found, SRT may be stopped and ADT started instead, or no active treatment if side effects outweigh potential benefits.
- No change to plan: Continue with SRT to the prostate bed, as originally intended. Here, the decision to treat is reaffirmed even if no change was needed.
The AUA Guideline specifically states the following: "Clinicians should inform patients that salvage radiation after Radical Prostatectomy (RP) poses inherent risks to urinary control, erectile function, and bowel function. These risks must be considered in the context of the risks posed by recurrent cancer along with patient life expectancy, comorbidities, and preferences to facilitate a shared decision-making (SDM) approach to management..."GROUP B: Proceeding to Androgen Deprivation Therapy (ADT) ADT is typically used when PSA is very high, PSA doubling time is rapid, or SRT is not feasible (e.g., prior radiation failure or technical reasons)The clinical assumption here is that microscopic metastatic disease exists, even if imaging can't yet detect it.
An experimental 64Cu-SAR-bisPSMA scan detects lesions:
This can lead to:- A change of plan: For example, if localized disease is detected (e.g., in the prostate bed or lymph nodes only), local therapy like SRT could be added to ADT, or switch from systemic-only therapy to combined modality. Alternatively, if very extensive disease is found, treatment goals might change (e.g., palliative intent).
- No change to plan: Continue ADT alone. Again, the decision to treat is reaffirmed, even if no formal change happens.
GROUP C:Observation (Active Surveillance / Watchful Waiting)Observation is typically chosen for Older patients (>75 years), Patients with significant comorbidities, Slow PSA doubling times (>12 months), Patient preference.
An experimental 64Cu-SAR-bisPSMA scan detects lesions:This can lead to:
- A change of plan: Initiate active treatment (SRT, ADT, or both) based on the new findings.
- No change to plan: Continue observation, if the clinical team and patient agree that the findings don’t warrant intervention (e.g., small-volume, indolent disease, high competing risks).
IN CONCLUSION
Even though it’s a bit more complex than first meets the eye – I hope the key point here is made. The impact of this scan is much more far reaching than what the number shows. 100% of the patients benefit from the scan. Thank God, I am on the right treatment already!
Thanks @JoboManduka for how you aptly put it: “… you would have to scan ALL your patients to know which half would benefit from a change to treatment plan…”!
In other words, every patient presenting to you with BCR and a negative SOC, has a 50% chance of being on the wrong treatment!has a 50% chance of being on the wrong treatment!
SOURCE DOCUMENTS
CLARITY documents
(20) Pre-SAR-bisPSMA Disease Management Form must becompleted by the treating physician to document the initial intended managementplan for the participant based on available clinical information andconventional imaging results.
(21) Post-SAR-bisPSMA Disease Management Form must becompleted by the treating physician for all participants who complete the 64Cu-SAR-bisPSMAPET/CT scan(s). The management plan will be based on the result from the localinterpretation of the 64Cu-SAR-bisPSMA PET/CT scan(s) to document whether achange to the initial intended management plan may be warranted due to the 64Cu-SAR-bisPSMAPET/CT finding(s).
EXTERNAL REFERENCESMorgan TM,Boorjian SA, Buyyounouski MK, et al. Salvage therapy for prostate cancer:AUA/ASTRO/SUO guideline part I: introduction and treatment decision-making atthe time of suspected biochemical recurrence after radical prostatectomy. JUrol. 2024;211(4):509-517. https://www.auajournals.org/doi/10.1097/JU.0000000000003892 (Read the following section)
- Treatment Decision-Making at the Time of Suspected Biochemical Recurrence After Primary Radical Prostatectomy (RP)
- Treatment Delivery for Non-Metastatic Biochemical Recurrence After Primary Radical Prostatectomy
Rahul D. Tendulkar, Shree Agrawal, et al. Contemporary Update of a Multi-Institutional Predictive Nomogram for Salvage Radiotherapy After Radical Prostatectomy https://ascopubs.org/doi/10.1200/JCO.2016.67.9647
ProstateCancer-SalvageRadiation-FS-2025-English.pdf 
(20min delay)