Androgen deprivation therapy (ADT) remains the principal treatment of advanced prostate cancer. However, most patients eventually experience treatment failure, resulting in castrate-resistant prostate cancer (CRPC). Loss of the tumor suppressor gene phosphatase and tensin homolog (PTEN) has been linked to poor survival in prostate cancer. We have recently shown that PTEN loss is evident in approximately 60% of prostate cancer cases in Jordan. However, the correlation between PTEN loss and response to ADT remains unclear. This study aimed to determine the relationship between PTEN loss and time to CRPC in Jordan. We conducted a retrospective analysis of confirmed CRPC cases at our institution from 2005 to 2019 (N=104). PTEN expression was assessed using immunohistochemistry. Time to CRPC was calculated from the initiation of ADT to the confirmed diagnosis of CRPC. Combination/sequential ADT was defined as the use of two or more classes of ADT concomitantly or switching from one class to another. We found that PTEN loss was evident in 60.6% of CRPC. Mean time to CRPC was not different between patients with PTEN loss (24.8 months) and those with intact PTEN (24.2 months; p=0.9). However, patients receiving combination/sequential ADT had a significantly delayed onset of CRPC compared to patients on monotherapy ADT (log-rank Mantel-Cox p=0.000). In conclusion, PTEN loss is not a major determinant of time to CRPC in Jordan. The use of combination/sequential ADT procures a significant therapeutic advantage over monotherapy regimens, delaying the onset of CRPC.
This study from Jordan lends further support to the SOC, hormone double blockade supplanting monotherapy in de novo metastatic hormone-sensitive PC. The article does not actually state the aforementioned state. My assumption of de novo mHSPC is based on the cohort's baseline median PSA of 172. This high number suggests there are few recurrent metastatic patients in the cohort. That Pten, a commonly mutated tumor suppressor gene, in prostate cancer, is not correlated with castrate resistance, is a testament to how complicated and redundant the pathways are. The science of these pathways is still in its infancy. But with the accumulation of data and AI who knows ......
Note: The study shows that 30% of patients in their Jordan cohort were getting the substandard, monotherapy, as are many patients in the USA. Stated another way, many urologists in this country, even for treatment-eligible patients, are prescribing monotherapy; some 5 years after the beginning of the sea change circa 2017. The sea change of migrating 2nd generation ARSIs from their 1st FDA approved application in the mCRPC state into the earlier mHSPC space. Admittedly, there may be insurance and/or financial toxicity issues.
Two questions: 1. How does one have PTEN checked? It's never come up in five years, and 2. Combination/ sequential (if switching from one class to another) could mean switching from, say, Lupron to Firmagan or Orgovyx?
No, I just meant I read their definition of combination/sequential as including a switch from one first level to another (as in Firmagan to Lupron or vice versa). That's the way I understood it. It may be less important since few do that today.
1. The PTEN rearrangement is an intragenic deletion of exon 2. One of the breakpoints is within exon 2. 2. The TMPRSS2 - ERG fusion involves TMPRSS2 exon 1 and ERG exons 2 - 10.
MEAN OVERALL COVERAGE (SEQUENCING DEPTH) IN THIS SAMPLE: 356X
The following exons with OncoKB levels of actionability associations showed coverage of less than 100X. A false negative result cannot be excluded in these regions, especially in samples with low neoplastic cell content.
really? Are you sure, Magnus? I am so nervous since I found out yesterday that I have this PTEN mutation. Tall_Allen told me this gene speeds up the time to CR. But when I read your profile, I feel better that you are dealing with this for many years despite you having the mutation. Happy holidays
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Is this pointing to cancer becoming castrate resistant?
Intermittent Androgen Deprivation Therapy
Help: Metastasized Castration Resistant Prostate Cancer!
