Greetings FPC Members,
Metastasis Directed Therapy (MDT) is becoming a standard of treatment in oligometastatic patients. For my next items, I would like to see where we are using cryosurgery and thermal ablation (laser, radiofrequency or photodynamic) in MDT.
Since my initial post, I found an interesting article on treating oligometastatic Pca
ncbi.nlm.nih.gov/pmc/articl...
People ask why should we use MDT because isn't this “whack-a-mole” and once metastasis occurs then it is over, right??
Another hypothesis has come forth for explaining the rationale for aggressive treatment of oligometastatic Pca patients- A concept of “tumor self-seeding,” which suggests that circulating tumor cells can colonize their own origin of metastatic deposits. In other words, the primary tumor may act as a self-seeding site for circulating tumor cells to be primed and deposited at metastatic sites. This lends support to the notion that local therapy of the primary tumor and/or the metastatic deposits may inhibit the development of new metastases by altering the tumor microenvironment. An article on tumor “self seeding”:
ncbi.nlm.nih.gov/pmc/articl...
Thus, the basis for treating the prostate and oligometrastatic sites is to eliminate areas of seeding and prevent transmission of mRNA between existing tumors. This could theoretically help to reduce or eliminate resistance, enhance systemic therapy, alter the tumor microenvironment, possible abscopal effect, and ultimately...slow progression.
Recently, a study was done using cryosurgery with a check point inhibitor injected intratumorally with sangrostim and the results were impressive. Among the 19 evaluable PCa patients, there were 9 (47%) Complete Responses and no PRs, for an ORR of 47%. 5 (26%) patients showed Stable Disease, and 5 (26%) progressed. 13/21 (62%) of patients had post-therapy PSA reductions of >50%.
12 PCa patients were ADT-naïve (11 evaluable by RECIST) and there were 9 with mCRPC (8 evaluable by RECIST), and positive responses were seen in both groups, with ORRs of 55% and 38%, respectively, and PSA reductions of > 50% in 75% and 44% of patients, respectively. The article below:
abstractsonline.com/pp8/#!/...
Need I say it, but.... A COMBO....
From here a look at thermal ablation which may involve laser, radiofrequency, or photodynamic ablation. Below is an institutional study in treating oligometastatic disease in prostate cancer. This study included RF ablation and resulted in good control and delay of ADT.
sciencedirect.com/science/a...
Recently, Photodynamic therapy showed great potential for treating the primary using nanoparticles. One of the coming therapies is the Aurolase for those seeking initial treatment of prostate cancer using gold silica nanoshells—the article below:
sciencedaily.com/releases/2...
But Don...How do we find/target those mets just too small for a PET/CT or MRI?? I would suggest we start using nanoparticles that can target small tumors using substances like PSMA or EGFR—see below:
sciencedaily.com/releases/2...
So where is MDT headed regarding cryotherapy and thermal ablation?? Again, I believe we will see more trials involving combo therapy---MDT PLUS directly or indirectly into the tumors--. The use of check point inhibitors, immune system stimulators, nanoparticles with choose one: a) chemo, B) radiopharmaceutical, c) photodynamic capability.
I hope Part (2) of MDT has been enlightening and welcome questions...
Don Pescado
