Mets Day 898: Further consultations on my treatment options

Yesterday afternoon I sent the following email to Dr. Jeanny Aragon-Ching, my primary clinical oncologist at GW University:

Dr. Aragon-Ching:

Following up on my visit with you on Monday, September 8 regarding my PET-MRI scan results from NIH: Last week I was advised by Corrine Keen, Dr. Apolo's clinical nurse, that I was required to sign a consent form before NIH could send you copies of my scans. I have since signed and returned the form, so hopefully you should be receiving those scans soon. I would be most interested to hear of your thoughts once you have reviewed my most recent scan.

I had understood from our conversation on September 8 that you were going to check on the following:

1. What is the status of tissue from my cancer being sequenced? Has either GW or NIH sequenced my cancer, and if so, what are the results?  If not, is there sufficient tissue available to perform a genetic sequencing? The four sources of tumor available for biopsy would be as follows: 1) the fine needle aspiration at NIH on 9/5/13; 2) the bladder and nodes removed during my radical cystectomy at the University of Chicago on 5/2/12; 3) the TURBT performed by Dr. Fred Hendricks (GW MFA) at GW Hospital on 1/5/12; and 4) TURBT performed by Dr. Hendricks at GW Hospital on 12/1/11. FYI, I have checked with my insurer (United Health Care), and am advised that the cost of genetic sequencing is covered, provided that you obtain a preauthorization, and either send it to an in-network lab, or obtain preapproval to send it to another lab. According to UHC, the following labs are considered to be within the UHC network:

Myriad Genetics
Bioreference Labs
Integrated Genetics
Integrated Oncology

2. Regardless of whether there is tissue available from one of the older biopsies, does it make sense to have the tumor in the enlarged node biopsied and the tissue analyzed? Or is it sufficient to assume that the mets cancer in that node is identical to or sufficiently similar to the material that was biopsied at NIH on Sept. 5, 2013?

3. I understand that there is no definitive data on effect of lymphadenectomy [removal of the cancerous lymph node] and its contribution to survival on patients who continue to have nodal positive disease after chemotherapy. I have reviewed the articles with the following links, and wonder if I should further explore the possibility of lymphadenectomy.

EAU 2014 - The curative potential of lymphadenectomy after response to chemotherapy in patients with urothelial carcinoma presenting with regional or distant nodal metastases: Analysis of a series from a tertiary cancer centre

Postchemotherapy Lymphadenectomy in Patients With Metastatic Urothelial Carcinoma: Long-Term Efficacy and Implications for Trial Design.

Could a salvage lymphadenectomy after chemotherapy have clinical impact on cancer survival in patients with metastatic urothelial carcinoma

I understood your thoughts were that the data did not expressly support lymphadenectomy in my case, and that the risks likely outweighed the benefits. Is that correct? On the other hand, I have a hard time understanding why cutting out a growing tumor is a bad idea. If I wanted to further consider lymphadenectomy, with whom your you recommend that I speak?

4. You recommended that I relax and wait until my next scan (currently scheduled for 11/18/14 at NIH), and if that showed that the node was over 1.5 cm on the short axis, that I should consider one of immunotherapy clinical trials. Do you think that course gives me the greatest chance for increasing my overall survival?

Thank you for your ongoing care.

 Last night she responded with the following:

I have not received the scans from NIH yet but I've attached the genetic findings from your tumor from what Dr. Apolo has sent. [chart follows]

MRN	SoftPath ID	DNA#	Gene Sym	Gene Accession #	coding seq change	protein change	Interpretation
4993238	SB-13-5207	TCC-15	TP53	NM_000546.5	c.839G>C	p.Arg280Thr	Deleterious

The mutation is p53 which is not (as of yet) an actionable target per se. I don't think there's enough cells from the FNA [fine needle aspiration] to do more testing and the molecular testing that best fits our needs (if we are to do more testing) would be Foundation One Medicine or Caris Life Science testing, which are testing for drug targets (as opposed to the genetic tests run by Integrated Genetics or Myriad, etc which is used more for hereditary testing or diagnosis, for example).

While I do find merit in lymphadenectomy for localized disease, your area of lymph node involvement is truly difficult to resect out, and this would be the field of cardiothoracic surgery (because of where it is located) and because these are underneath the clavicular (collar bone) area, it would be very difficult to traverse (unlike say in the abdomen - usually a retroperitoneal lymph node dissection is done) because of the collar bone (which connects your shoulder to the breast bone, important nerves/blood vessels in a cramped space in that area that can leave your brachial plexus vulnerable).  We generally follow the rules of thoracic surgery (for instance, for lung cancer) where involvement of these upper level supraclavicular nodes would generally preclude surgery as an option. 

I acknowledge that it is very hard to "relax and wait" in the face of these circumstances and I am painfully aware of the uncertainty that this entails.  If we did not have the immunotherapy option and the burden of disease is much more (meaning the size is way bigger and more disease is seen in your next scan), then I would favor chemotherapy still (therein lies the next question of which chemo).  However, if the adenopathy has just ever so slightly increased but to the point where you are eligible for the trial, then I think it's well worth considering it because of toxicity reasons (potentially less toxic perhaps).

Take care, JBA

This morning I'm still mulling over this information. I don't understand the information from the genetic findings, and will be doing some further readings about understanding genetic information generally, and the p53 mutation specifically. Also, I'm somewhat confused because I was previously told by several of my doctors that my bladder cancer had a large number of mutations; whereas this genetic finding identifies only one mutation. Maybe it was because the genetic screening did not test for all mutations, or because it stopped after finding the first mutation, or maybe it's because my metastatic bladder cancer has only a single identifiable mutation.

I'm also mulling over the information regarding lymphadenectomy. I understand Dr. Aragon-Ching to be saying that, if the node were somewhere else, lymphadenectomy might be a better option, but given it's current location, the risks outweigh the benefits.

I have no problem waiting and seeing, provided that is the best option. Heck, I've been doing that for more than two years; waiting and seeing for 15 months after my RC surgery, until the distant nodes popped up; get nuked with ddMVAC chemo; then wait and see for another year. If waiting and seeing is truly the best course, then I'm all for it. It's just that I'm not fully persuaded at this point.