For what its worth, on a boring Monday, with the market seemingly in foul mood, for reasons I can not fathom, let me add some views to the article referred to above: Thanks
@ma420 for your prolific 'search and find' capabilities! The more we know, the better for us all, I feel!
The article is a summary of an abstract by Soumyajit Roy et al, that was presented at the recent ASCO GU conference (ASCO 2025). That source abstract is titled:
Radical prostatectomy (RP) versus radiotherapy (RT) in high-riskprostate cancer (HR-PCa): Emulated randomized comparison with individualpatient data (IPD) from two phase III randomized trials (RCTs).In their research, Soumyajit Roy and co, used data from 2 older papers from around 2018/2019; one evaluated RP (CALGB 9023) and the other was on RT (NRG/RTOG 0521). They were separate studies, done at different times, by different groups.
What Soumyajit Roy and co did, was to extract data that was derived from the patient group of interest that was common in those two studies: patients with a diagnosis of
Localised High-Risk ProstateCancer, who were treated by the two treatments of interest; RP (plus) and RT (plus).
- [RP Paper] CALGB 90203: Radical Prostatectomy (RP) with or without Neoadjuvant Chemohormonal Therapy (CHT) in Clinically Localized, High-Risk Prostate Cancer; Clin Oncol. 2020 Sep 10;38(26):3042-3050. https://pubmed.ncbi.nlm.nih.gov/32706639/
- [RT Paper] NRG/RTOG 0521: Effect of Chemotherapy With Docetaxel With Androgen Suppression and Radiotherapy for Localized High-Risk Prostate Cancer (2019). J Clin Oncol. 2019 May 10;37(14):1159-1168. https://pubmed.ncbi.nlm.nih.gov/30860948/
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FIRSTLY – some Definitions & Reminders
What is Localized high-risk prostate cancer? This is prostate cancer that is
containedwithinthe prostate gland but has a high risk of spreading. Treatment is highly recommended in this group, particularly because its still
localised, and treatment should prevent the cancer from spreading outside the prostate!
- RP(Radical Prostatectomy): A surgical procedure to remove the entire prostate, and in the process, the entire cancer lesion!
- RT(Radiation Therapy): This is where the prostate is irradiated in order to kill the cancer cells. This irradiation is either through External BeamRadiation (EBRT) or other methods.
But how do doctors decide if the cancer is localised?- ConventionalImaging: This includes MRI, CT, and Bone Scans. This is what was used. Unfortunately, these methods often miss small lesions – hence, wrong diagnosis leading to the wrong treatment!
- PSMAPET Imaging: This now Gold Standard prostate cancer imaging modality is more accurate than conventional imaging. Examples include Pylarify and Illuccix (highest grossing), and the still in Phase 3 next generation Best in Class 64Cu-SAR-bisPSMA.
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Study Findings DiscussionThe 2 studies that provided the data to the Soumyajit Roy et al study, were done at a time before PSMA PET of any kind became the go-to for prostate cancer imaging and staging. We can see, right from the start, that the
risk of missing metastatic cancer was high for these men, meaning that the treatments (RP and RT) were perhaps used in a manner that did not suit the situation, due to these results.
Illuccix or Pylarify, would certainly have helped! 64Cu-Sr-bisPSMA would have done even better! But they were not available (or readily so).
[But, it is worth stating that, for this research, that deficiency affected both groups, so the analysis by these authors is not affected!]
RESULTSThe report states that "...
Before weighting adjustments,patients in the RP cohort were significantly younger and had lowerbaseline PSA levels than those in the RT group...". With all things equal, and since this measure represents ‘patient demographics’, the fact that there are significant differences in the groups, right at the outset makes this look like selection bias; such as a situation where, perhaps, doctors favoured
RP for younger patients and those with
lower PSA levels, while sending older patients and those with higher PSA levels to RT! This is not so straight-foward because no selection ever took place: the studies were done separately and on a cursory look, appear to have been independent of each other. Anyhow, this finding does impact on the analysis and the rest of the results and conclusions, making them 'arguably' invalid!
But, we will proceed!
Metastasis Rates: RT-based strategies showed a lower occurrence of Distant Metastasis (DM). The 8-year cumulative incidence of Distant Metastasis (DM) was 16% in the RT cohort, versus 23% in the RP cohort (P=0.01). This suggests that, RT (Radiation Therapy) prevented more future metastasis events than RP (prostatectomy).
Survival AfterMetastasis: The Death rates after DM were similar at 10% (for RP) and 8% (for RT). However, RT patients had a higher risk of death without metastasis – ‘suggesting some unidentified confounding factors’. I think age may have been a factor here: the older folks were sent to RT - they benefitted more from this as they did not go on to have metastasis diagnosed - but they still died sooner! Age and other diseases that come with age, I would guess!
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WHAT’S IN IT FOR CU6 INVESTORS!The relevance of this study to Cu6 holders and their 64Cu-Sar-bisPSMA, 67Cu-Sar-bisPSMA, individually or as a the perfect pairing, is tied to the findings from the PROPELLER, COBRA, and SECURE trials. More so to the PROPELLER trial (and predicted CLARIFY results) as the groups are the same: they are pre definitive treatment.
a) By relying on Conventional Imaging, it is likely that many cases that got Localised disease already had cancer cells that had escaped from the prostate at the time of initial treatment. In other words, some of these localized cancers were Metastatic Cancers at their original treatment.
b) IF it had been available and used, 64Cu-Sar-bisPSMA would have reduced the number of cases incorrectly classified as localized prostate cancer, leading to different treatment planning for these patients (COBRA Trial - Drs intentions). What is the point of removing the prostate or radiating the groin if there are already 50+ lesions in distant sites like the lungs and brain?
c) Since patients testing negative for metastases with 64Cu-Sar-bisPSMA are far more likely to be truly negative, result from the same treatments that were administered would be expected to be better than what was observed; there would have been lower rates of later-diagnosed DM.
d) If Radiation Therapy (RT) is indeed superior to Radical Prostatectomy (RP) (as shown in the study), then it perhaps Targeted Radiation Therapy using 67Cu-Sar-bisPSMA should perform even better than External Beam Radiation, due to the precision and the ability to seek out micrometastatic lesions that conventional imaging often misses.
e) If the hypothesized superiority of 67Cu-Sar-bisPSMA is confirmed, and considering the safety profile demonstrated in the SECURE Trial, we would expect 67Cu-Sar-bisPSMA to become the RT of choice, and hence reach FIRST-LINE treatment for men with localized high-risk prostate cancer!
The END!
GLTAH
(20min delay)