By: Dan Sperling, MD

The ability to detect prostate cancer (PCa) cells in the blood before prostate surgery is a recent breakthrough in predicting which patients are more likely to have recurrence after treatment. The cells are called circulating tumor cells (CTCs). When CTCs are present in blood samples before treatment, it increases the probability that free-floating cells can infiltrate other tissues and begin to grow as a separate tumor. For PCa patients, high CTC counts at baseline are considered a poor prognostic sign and an indication that a treatment other than radical prostatectomy be considered in order to not put the patient through the surgery and its side effects only to have treatment fail.[i]

However, CTCs are not a doom-and-gloom situation. It’s not easy for individual breakaway PCa cells to survive a journey in the bloodstream in order to implant elsewhere. Lone PCa cells have to break free of the tumor’s connective tissue, and then penetrate through the wall of a blood or lymph system vessel. Although cancer is a fearsome disease, individual cancer cells are usually vulnerable because they are often not as hardy as healthy cells. If they make it into the bloodstream, they are subject to attack from the immune system’s white blood cells whose job is to destroy alien cells, bacteria, viruses, etc. Finally, if they make it to the point where they can work their way out of a blood vessel wall, they still have to embed in an organ and begin to multiply and build a new tumor blood supply (angiogenesis).[ii] Because of this, recurrence is not necessarily inevitable among PCa patients with CTCs before treatment.

While this is reasonably reassuring, there is new evidence that radical prostatectomy itself can trigger activity of existing CTCs as well as release new tumor cells into the bloodstream where they become CTCs.[iii] There are several intraoperative issues that can promote this, chief among them:

1. The cutting, pulling and handling of the gland and its surrounding structures during surgery damage the integrity of the tumor capsule and its blood vessels, thus permitting cancer cell breakaway.
2. It is not physically possible to effectively tie off all blood vessels leading to and from the gland before removing it, resulting in spillage of blood that may contain tumor cells.
3. Some breakaway cells may have a greater ability to develop metastatic tumors.
4. The stress of surgery appears to amplify the invasive capacity of cancer cells.
5. It also seems to activate surface proteins on cancer cells that act as adhesion agents, allowing them to stick to the inner surface of blood vessels as well as to each other; from there, if they work their way through the blood vessel wall, they can embed as small clusters in other organs or bone.
6. Post-surgical biochemicals needed for wound healing, including the building and connecting of blood vessels at the wound site, can be opportunistically used by rogue cancer cells to initiate construction of their own blood supply needed for their survival.
7. Anesthesia and pain control medications can suppress the immune system so it is less able to combat CTCs.
8. Another factor that is often overlooked is the psychological fear, anxiety, and experience of pain, all of which release stress hormones in the patient that further down-regulate (diminish) the functionality of the immune system.[iv]^{, [v]}

A 2009 study by Eschwège et al. gives a measure of how often prostatectomy results in the release of CTCs.[vi] They enrolled 155 men with biopsy-proven PCa who were to undergo radical prostatectomy and whose clinical factors were known. Blood draws (to measure CTCs) were taken a day prior to surgery, and again 5 minutes after the prostate was removed. The blood samples were analyzed for tumor cells and biomarkers (the methods used were tested on samples from 100 healthy volunteers and no false positives occurred, thus validating the blood analysis methods).

CTCs were found pre-operatively in 57 patients (37%). The remaining 98 patients (63%) had no evidence of CTCs before they went into surgery. Of those 98 patients, 45 (46%) became positive for CTCs during surgery. All patients were followed for a median of 36.2 months. Recurrence rates were highest among the 57 patients who had CTCs before prostatectomy; recurrence rates were lower for the other 98, and were roughly equivalent between those who became CTC-positive during surgery and those who did not. The authors concluded that the existence of pre-treatment CTCs was a significant predictor of post-treatment recurrence.

On the other hand, evidence from a breast cancer study suggests that three-year follow-up is insufficient to assess the threat posed by surgically-released CTCs. Demicheli et al. discovered that among breast cancer patients, there was a distinct mortality peak “at 7–8 years after surgery, suggesting that beside its important beneficial outcomes, surgery may indeed have long-term deleterious effects.”[vii] This suggests the need for longer term outcome studies on surgically released CTCs, since pre-existing circulating cells would seem to have had a head start on metastatic tumor development.

A 2009 article by Steven Nemeroff, ND in Life Extension Magazine offers suggestions for reducing the chances of scatting cancer cells during cancer surgery.[viii] One way, of course, is to choose a less invasive treatment for the same condition, assuming it has competitive results and the patient is a good candidate. Perhaps the ever-increasing interest in focal prostate cancer treatment is connected to a better understanding of the potential harms of surgery that don’t become apparent for several years. Treatments like focal laser ablation (FLA) do not involve surgical manipulation of the gland, and the extreme heat of the laser energy cauterizes (seals off) blood vessels while it immediately destroys tumor cells. The Sperling Prostate Center protocol includes several advantages that minimize any risk of disseminating tumor cells while maximizing the body’s own immune system defenses:

• No major surgery, no blood spillage, no disruption of the tumor due to manipulation
• Extreme laser heat cauterizes (seals off) tumor blood vessels
• No general anesthesia to suppress the immune system
• Relatively short outpatient procedure reduces patient fear and anxiety
• Absence of pain controls production of stress hormones

Focal laser ablation offers competitive cancer control with minimal side effects. Unlike prostatectomy, FLA leaves all future treatment options open, including a repeat focal treatment. Thus, FLA helps avert the problem of prostate surgery releasing cancer cells into the bloodstream.

[i] Friedlander T, Fong L. The end of the beginning: circulating tumor cells as a biomarker of castration-resistant prostate cancer. J Clin Oncol. 2014 Apr 10;32(11):1104-6.

[ii] http://www.lifeextension.com/magazine/2009/12/preventing-surgery-induced-cancer-metastasis/page-01

[iii] Neeman E, Ben-Eliyahu S. The perioperative period and promotion of cancer metastasis: New outlooks on mediating mechanisms and immune involvement. Brain Behav Immun. 2013 Mar; 30(Suppl): S32–S40.

[iv] Neeman and Ben-Eliyahu. Ibid.

[v] Eschwège P, Moutereau S, Croupy S, Douard R et al. Prognostic value of prostate circulating cells detection in prostate cancer patients: a prospective study. Br J Cancer. 2009 Feb 24; 100(4): 608–610.

[vi] Ibid.

[vii] Demicheli R, Valagussa P, Bonadonna G. Does surgery modify growth kinetics of breast cancer micrometastases?

Br J Cancer. 2001 Aug 17; 85(4):490-2.

[viii] http://www.lifeextension.com/magazine/2009/12/preventing-surgery-induced-cancer-metastasis/page-01