Organ confined but cancer comes back, why

Cancer cells leaving the prostate appears not to be uncommon--these are circulating tumor cells or CTC. (Procedures like a TURP or biopsies are not thought to promote metastases). Fortunately these CTCs have have an exceptionally difficult time establishing themselves in tissue outside the process--mets in lymph nodes, bone, the lungs, liver, bone, etc. However, in some men, over time, prostate cancer cells do gain the this ability. One study that looked the genetic variations in prostate lesions and mets found that in many cases all the mets a patient has can be traces to a single lesion in the prostate--not a single Gleason grade set of lesions, but a single lesion! This would attest to just how difficult it is for PCa to metastasize. (I have read that men with mPCa do have larger number of circulating tumor cells, but I believe men who would never develop mPCa can have CTC as well.)

Why do these men go on to recurrent disease? In some cases it is thought that the metastatic process began and micromets formed even though the cancer was apparently prostate-confined with no positive surgical margins at the time of surgery. In other cases microscopic positive margins might have been missed, or a fragment of viable prostate tissue was left behind. (Also, we should limit the discussion to truly prostate-confined cases as determined by the path staging and not include cases where the surgeon said "essentially prostate confined" or "that small margin or small EPE isn't significant.) We tend to see Forum Brothers who are in this 5-10% and not the other 90-95% who don't have BCR. Finally, not all cases of BCR go on to clinical recurrence (detectable lesions/mets).

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Oncologic outcomes of organ-confined Gleason grade group 4-5 prostate cancer after radical prostatectomy (2021) (Abstract only is free).

From the Full Text:

"Radical prostatectomy (RP) is one of the main treatment options for localized prostate cancer. RP in patients with organ-confined prostate cancer (CaP), defined as pathological stage T2 (pT2), and negative surgical margins (NSM) is associated with good long-term outcomes. Those patients are considered to have the least risk of biochemical recurrence (BCR). But in a small subset of patients, recurrence does occur. At 5 years, even in patients with favorable pathologic characteristics at RP, BCR occurs in 5%-10% of patients."

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To clarify, micromets are just microscopic metastases in place somewhere that escape detection by the current best imaging techniques. They are distinct from CTCs. There are now commercial tests to measure CTC (e.g. CELLSEARCH®-, ISET®-CTC), but, so far at least, I don't think CTC measurement has gone from application in research studies to everyday PCa diagnosis, but this may change:

New Screening Test Improves Detection of Prostate Cancer Using Circulating Tumor Cells and Prostate-Specific Markers (2020)

Take home message: the name of the game is early diagnosis of PCa coupled with expert advice to know if and when it is necessary to take action to prevent metastatic disease before it begins.

Djin

Fauntleroy said...
Over the years, I’ve seen many instances of recurrences after RP surgery where the original pathology report came back “organ confined, clear margins”
Since the prostate has been removed with no evidence of cancer surrounding the area when the tissue was examined microscopically, where’s it coming from?
Isn’t there any kind of blood test to pick up circulating micromets, if that’s what it’s from.
And would surgery or a turp release cancer cells into the bloodstream during the procedure itself?

surgery does not treat the prostate bed like radiation.

My surgeon confidently told me that he “got it all” after the surgery and the pathology results came in, despite the fact that the report indicated LVI. I believed him and sent him a handwritten note afterward thanking him for saving my life. 3 months later my PSA was high which resulted in SRT (at another practice). I guess you never really know with PCa…

Very helpful and informative, thanks.
What a complicated disease.

LVI is invasion of cancer into the fine lymph and blood-vessel network within the prostate as seen under the microscope during the path exam after the RP. In other words, visual evidence the cancer has entered the blood/lymph flow within the prostate. It is not the establishment of cancer within the walls of the lymph/blood vessels.

"LVI was defined as the presence of cancer cells within an arterial, venous, or lymphatic lumen on routine hematoxylin and eosin sections." reference
[Lumen is the key word. The lumen of a vessel is the space within it that carries the flow.]

The reason it's an adverse finding is the concern that the cancer has already left the prostate via this transport network and seeded, for example, local lymph nodes. Cancer is usually treatable by RT as long as it's in the radiation field; it doesn't matter if got there by contiguous spread, the lymphatic system, or blood flow.

LVI itself is not proof that metastases have formed outside the prostate.