Wednesday, March 21, 2018

CR 1002: The significance of this CT scan is not clear

Twelve weeks have passed since my last CT scan just prior to Christmas. On Monday I had another CT scan of my neck, chest, abdomen and pelvis. I think that I’ve had more than 30 CT, MRI or PET scans since I was first diagnosed with bladder cancer. This time, the actual was uneventful – the tech got my vein with the first stick. Yesterday morning, a Kaiser oncology nurse emailed the results: “CT shows slight increase in a chest/mediastinal lymph node. The significance of this is not clear.” Humph. Not a useful analysis. So I got a copy of the scans on disk and took them with me to my appointment with Dr. Hahn at Johns Hopkins yesterday afternoon. He said that he was not worried about the slight increase in the size of the node, since there was no sign of metastatic activity. We both knew that the Hopkins radiologists would closely review the images and compare them to my prior scans.

My lab work was likewise unremarkable, except for a slight increase in alanine amino transferase (ALT), an enzyme that measures liver function. Dr. Hahn said that the increase was still within the normal range and didn’t see the need to take any action at this time, but we should keep an eye on it. He suggested that I do labs every month instead of every three months to see if the ALT level continued to increase. All in all, these results are not bad. There continues to be no evidence of disease. But it’s not a clean bill of health, either. So I’ll muddle on.

Dr. Hahn and I also talked about my recent appointment as a patient advocate on the Bladder Task Force, which is part of NIH’s National Cancer Institute Steering Committee program. The BTF regularly reviews proposed clinical trials relating to bladder cancer. My job is to look at the proposals from the viewpoint of a patient – e.g., would this be a trial that would be attractive to a patient, as opposed to the standard of care; what is the likelihood of a substantial benefit; how can the investigators reduce the burdens on the patient; etc. Dr. Hahn encouraged me to speak up and remind the MD’s and PhD’s how it feels to be on the other end of the needle. “Sometimes researchers get caught up in the science and lose sight of the patient,” he said.

In other news, the spring real estate market is heating up. In the past two weeks we’ve received two offers on our house. We rejected a lowball without bothering to counter. We’re preparing to counter another one. We’ll see what happens. My more immediate concern is shoveling the 6-8” of global warming that has fallen on this second day of Spring.

Tuesday, December 26, 2017

CR 917: A reminder of how quickly things can change

Last week I had another CT scan at Kaiser. That afternoon the Kaiser nurse told me that the scan looked fine, with no evidence of metastatic activity. Two days later I drove up the Hopkins to check in with Dr. Hahn. He likewise saw no metastatic activity, but noted that my supraclavicular node (or a collection of two or three nodes) had increased in length by 3 mm. The node that showed up on the scan is the same location and the node that first started showing metastatic growth back in August 2013. It’s the same one that was biopsied in September 2013 to confirm my distant mets. And it’s the node that has shown the greatest elasticity, growing to over 4 cm in March of 2015, then shrinking to almost nothing by the end of the year.

The node did not “light up” in response to the contrast, so there is no indication that there is active cancer growth. But it was bigger in size. Maybe it was the way it was sliced in the scan, or maybe the nodes have sort of fused together, but it was the first increase in size of any of my nodes in more than two years. Dr. Hahn didn’t seem bothered by it, however, and we talked about increasing the time period between scans from the current 12 weeks (the duration I’ve been maintaining for more than 5 years) to 16 weeks. He and the new Hopkins clinical trial nurse are going to check with the trial sponsor (Bristol Myers Squibb) since the trial protocol is unclear on whether the duration between scans can be increased and the patient data still be included. I’m fine with whatever they decide.

So the report is good – no sign of metastatic cancer – but it’s a reminder that the durability of my remission is uncertain. I continue to sail through uncharted waters, with no one having gone before me to provide any expectation of what lays ahead. Stay tuned to see if I discover dragons or sail off the edge of the world.

In other news, two weeks ago I totaled our car in West Virginia. I was driving in Blackwater Falls State Park soon after a glazing of snow, tapped on my brakes as I was entering a curve, hit black ice, slid down a hill and crashed into the side of a large culvert. I was with Jennifer, Spencer, and Nephi, and fortunately we just got some bumps and bruises. But it was another reminder of how quickly life can change. I was grateful that all of us were able to walk away. I'm also grateful for the good in the world, and for the spiritual gifts during this holy season.

Friday, September 29, 2017

CR 827: Another good CT scan (I think)

On Tuesday I went into Kaiser for another CT scan. Drank the banana smoothie-flavored barium contrast 4 hours and 2 hours in advance, got my blood drawn for my labs, then had three more sticks as a rookie CT tech fished in my arms for a vein. I wish that Kaiser could just use the same needle and vein for my CT as they do for the labs, but that would take planning, coordination, and concern for the patient. I have never quite mastered the art of patience while nervous techs try multiple times to properly place an IV. I am not your pincushion.

Once everything was in place, the CT took seconds. Following injection of the ionic iodinated contrast, I felt the familiar feeling of warmth as it triggered an increase in intravascular osmolality, causing a shift of water into the veins. This increase in blood volume caused vasodilation that spread throughout my body in seconds, lodging in my pelvis. Cancer has significantly improved visibility with iodinated contrast. 

I've long gotten over "scanxiety" -- the fear of what a CT may reveal -- since I've accepted that a CT is purely retrospective: it shows what has already happened. Plus, I'm utterly at peace with the fact that I don't control my cancer, and learned long ago not to worry about things I can't control. I have, however, thought about the frequency of my CT scans -- I've had nearly 30 in the past 6 years -- and whether the 20+ milliverts of radiation exposure is worth the risk. I've shrugged my shoulders and assumed that its far more likely that my mets BC likely will kill me before any CT-induced cancer could manifest itself and willingly laid down on the scanner.

After the scan was done, the fisherman tech reminded me to drink lots of fluids, which I consistently interpret as medical orders to go to McDonalds for some sausage and egg burritos and several liters of Diet Coke. I slurped my soda as I drove down to Lake Anna to get another load of stuff from our lake house, which is finally under contract. It will be good to unload that -- we had lots of good memories there, but with our nest empty it's time to let someone else enjoy it. 

As I was returning home, a nurse from Kaiser called me with the results of the CT. She said that the radiologist had not seen any signs of new metastatic activity. Yay! However, the radiologist detected a new scar on the upper right lobe of my lung, about 13 mm long and 3 mm high. She could not determine what caused the scar, but did not see it as a cause for concern. "We'll continue to watch it," she said. Humm. I was glad that I was scheduled to go up to Hopkins on Thursday to check in with Dr. Hahn as part of my follow-up for my clinical trial. I wanted his thoughts.

Yesterday I drove up to Hopkins with the CD of my scan. Dr. Hahn spent some time studying the CT scan, and could not make out what the Kaiser radiologist had reported. He said he'd have the Hopkins radiologists study it, but saw no cause for concern. 

We also discussed the latest durability data. He said that the longer term data from immunotherapy patients in other trials with other malignancies (mets melanoma, kidney, lung) continued to suggest that patients who got to 24 months of remission lad a low risk of recurrence. From a biological standpoint, he thought that it was highly likely that all of my cancer cells that had the PD-1/PD-L1 interaction had been destroyed by my body's immune system. There was always a possibility that I had some stem cells harboring that type of cancer, but as time goes on it becomes less and less likely that it would manifest. The bigger question is whether another mutation would start growing. Dr. Hahn had previously told me that was the most likely thing that would happen. But as time goes on, the likelihood of that happening decreases. These thoughts continue to be assumptions built upon extrapolations built upon suppositions, since "I am the data" for metastatic bladder cancer durability. 

We also discussed the frequency of future CT scans. Dr. Hahn wanted me to have another scan in 12 weeks, which would bring me to one year after ending my infusions of nivolumab. He could not remember if the clinical trial protocol contained guidelines for the frequency of CT scans following 1 year of completion of treatment, and would look into it. He suspected that at some point, he'd want to shift from 12 week intervals to 16 week intervals, and eventually to 26 week intervals between scans. I'm ok with that. 

Today, I received the report from the Hopkins radiologists. They compared this scan to the 13 earlier scans that I have had since February 2015 (when I started the clinical trial), and saw no new lesions. My target lesions -- the tumors that they used to determine the success of the Opdivo -- continued to be totally undetectable. My non-target lesions (other tumors of note) also continued to be undetectable. So what did the Kaiser radiologist see? To quote Shakespeare in Love: I don't know. It's a mystery.

October 9, 2017 addendum: Dr. Hahn sent my CT for a second opinion, and today that reading was posted by Hopkins in my chart. The radiologist saw no evidence of any metastatic activity or other abnormalities, other than "patchy bilateral ethmoidal mucosal opacification" e.g., some solid mucus in my sinuses. Woot.

Wednesday, September 13, 2017

CR 811: Q&A with other BC patients

Each week I receive an email with new questions regarding bladder cancer that are posted on the BCAN section of I sift through the questions and comment on topics on which I have some experience and where I think my post may help. Here is a sample of the recent questions and answers:

Stage 4 UC. The bladder cancer is now in my left lung. I meet with trial manager Monday Sept. 11 to see if I'm a candidate. 3 arms to trial (due to 1 kidney here are drugs I'm eligible for).
Arm A: Atezolizumab + carboplatin ,gemcitabine
Arm B: Atezolizumb monotherapy
Arm C: Plecebo + carboplatin, gemcitabine
Do any of you have any insight on this trial?
On a different note, Is there any outcome advantage for immunotherapy versus chemotherapy?
I Look forward to your responses.

My response:
Trimodal therapy (arm A) is very promising, but your other health issues are a concern. Atezo alone (arm B) would have the fewest side effects, and most likely to help with your mets. Chemo only (arm C) is the standard of care. With lung mets and your comorbidities, I'd push for the immunotherapy, and have chemo only if your docs thought I could tolerate it well. But I'm not a doctor so if they tell you anything different, listen to them. Good luck and God bless, Ken

I signed consent forms today for a clinical trial with MSKCC, my current doctors. I will receive opdivo and yervoy every 3weeks for four doses and then only opdivo every 2 weeks for two years unless toxicity occurs or if cancer progresses.
Liver biopsy, protocol labs and tests tomorrow.
I told him I wanted an aggressive and out of the box treatment, he said this is it.
Hopefully I'll do okay with the first four doses. Wish me luck. I'm very nervous about side effects.
Has anyone done a two immunotherapy clinical trial?
Appreciate any info

My response:
I enrolled in a precursor to your trial, and was randomized into the nivolumab only arm. I got 46 doses and have had a complete response - no evidence of disease -- that's ongoing and has lasted for more than two years. I've detailed my exeperince on my blog at (start in 2/2015).

As I'm sure you're aware, adding ipi into the mix increases the risk of class 3-4 side effects. Create a baseline chart of your physical health now - including bowel movements, skin condition, fatigue (how many minutes can you do x), and continue to keep up that chart while you are on the trial.

I just returned from the 2017 BCAN Think Tank, and heard how combination therapy of two, three, or more drugs is the next frontier for for mets BC. It pays to keep current with the research, because treatments are changing so quickly!

Good luck and God bless, Ken

My husband was diagnosed a few weeks ago with stage IV bladder cancer (invasive high-grade urothelial carcinoma) which has spread to his prostate and three of the pelvic lymph nodes. His oncologist told us that since the cancer was already in the lymph system, he was not a good candidate for surgery to remove his bladder, prostate and lymph nodes because the cancer "seeds" have likely already spread. However, the urologist that we were referred to after his diagnosis felt that surgery might still be in his future. We are going to seek a second opinion, but I am just curious to hear if other men diagnosed at stage IV had the bladder/prostate/lymph node removal surgery done?

My response:
Gary Steinberg at U. Chicago did my RC and neo after I was Dx'd with cancer in my nodes. He was pulling lymph nodes like weeds, and got 62 of them. 12 were positive. That was over 5 years ago and I'm still going strong, although it's been a roller coaster. Details are on my blog at The takeaway is that there is hope for your husband. Get to an NCI center -- Mayo, or Gary at U. Chicago. Don't delay therapy. Consider immunotherapy now, or have the RC then immediate immunotherapy. It's possible to live for many years despite lymphatic metastatic cancer, but you and your husband need to be proactive! PM me if you or your husband want to talk off-line. Good luck and God bless, Ken.
I've been stage 4 since my RC in 2014 and finding several lymph nodes positive for bladder cancer. I've been getting regular follow-up scans that show very small nodules, some in my lungs, and swollen lymph nodes in the groin, but I've received no treatment and generally feel very good, energetic, and a lack of symptoms. However, these small nodules are showing "slow but steady progression" and I've recently had some deep pain that may/may not be related to BC. Talking to my oncologist about the drugs currently approved for immunotherapy, he said Kaiser would likely use either Teqcentric or Keytruda, and that they use Keytruda quite a bit there for other cancers, so he's very familiar with it. Hence my question: is there any basis to prefer one of these to the other? I didn't have a very effective response to gem/cis chemo in 2014, and it felt like it took a year to recover, but it seems to me that if I need treatment, it would make more sense to start with immunotherapy. Any thoughts?

My response:
I vote for getting on an immunotherapy drug. Which one isn't as important as the fact that you're on one. They work in a similar way, so don't get too hung up on choosing the "correct" drug. As for me, I had 46 rounds of nivolumab (Opdivo) and had a complete response, which is ongoing for more than 2 years. Details are on my blog at A recent journal article about immunotherapy is "Checkpoint inhibitors: the new treatment paradigm for urothelial bladder cancer" at (Med Oncol (2017) 34:170). The bottom line is that immunotherapy is changing the way mets BC is treated, and everyone with mets should consider getting one of those therapies.

I'm looking for a surgeon in the Chicago area to conduct a radical cystectomy with neobladder diversion and currently have this shortlist:
Dr. Gary Steinberg (U of Chicago)
Dr. Norm Smith (U of Chicago)
Dr. Marcus Quek (Loyola)
Do you have any recommendations for choosing among them?  

My response:
Gary Steinberg did mine in May 2012 and I'm still alive despite 12 positive nodes. Details are on my blog at (go to May 2012). I can't speak about the other two. Go with your gut (so to speak . . . )

Hi. My husband is 43 and has metastatic bladder cancer. I need some advice. He was diagnosed last October with stage 3 muscle invasive bladder cancer, went through 6 months of preoperative chemo, and then this July had his bladder removed and a neobladder placed. His cancer spread to his lung and liver and is now undergoing Immunotherapy (Opdivo) while still recovering from the neobladder surgery. Is there anyone out there possibly going through the same thing? He has been in and out of the hospital ever since the surgery for either infections or constipation issues. Any advice on foods your eating, how much liquids you're drinking, tips?
Thanks so much

My response:
I'm 5+ years post neo and stage IV. The recovery from a neo is made harder with the knowledge of mets. I've blogged about my journey at Your husband is getting the right immunotherapy and should know in the next couple of months if it is working, but it sounds like he may need some counseling to help realize that his life isn't over yet. Your hospital may have oncology social workers. Get some one-on-one with a counselor for him, and for you too. Being a caregiver is hard work (or so my wife says). Even if he won't go, you should. Hang in there! Ken

My husband has bladder cancer. He told his doctor he saw a little blood in his urine only 2 or 3 times with in 2 years and the doctor said without checking that it's a uti and it's common for men in there 60s. Finally was told go see urologist who told him he was loaded with tumors in bladder. Did bcg treatments which did nothing. The tumor continued to multiply. It's an aggressive cancer. Went to a doctor who specializes in bladder removal. Dr said cancer is contained in bladder. Had his bladder and bunch lymph nodes removed and a new bladder made. Doctor said he is cancer free and a survivor will live 20 more years. After about a year doctor said you need to go see another dr you have 5 spots in your lungs. Come to find out he had been watching them on all the routine tests. Went to Dana-Farber and had pet scan. He has approximately 35 plus tumors in BOTH lungs, his kidney was lit up like a spot light and he had 2 spots behind his stomach. Dr said he has a year to live. Talk about SHOCK. He was treated with gemzar and cisplatin for 6 months 2 weeks on one week off until he told the dr he would rather be dead due to the awful side effects. His tumor did shrink a little from it but his body just couldn't take it any more. We asked for immuno therapy tecentriq recently approved for bladder cancer. Its been three months of treatment once a week for half an hour and scan shows a little growth of tumor but they are still smaller than at first. Side effects are nothing compared to chemo. He does have neuropathy in hands and feet. His feet kill but he just keeps going. He is being treated for another 3 months and will have another scan. If they grow he will have to try chemo again.😞 We are praying this immuno therapy works. A good word of advise would be when diagnosed with cancer go to a good cancer specialist. We didn't realize that and my husband is paying the price.

My response:
I've been stage IV for more than 5 years. Two different types of chemo helped slow the growth, then a clinical trial with Opdivo wiped out all my tumors. I've been cancer-free for more than 2 years. Details are on my blog ( Immunotherapy doesn't work for everyone, but it's the best option out there for those with Stage IV. New combination therapies are being tested, and some show great promise. Everyone with Stage IV should get to an NCI hospital and get educated on all the options. Treatments are changing quickly, and you need to be working with doctors who are current on all of the most recent therapies. It's especially important for patients to be proactive and push their medical teams for the best options.

Hello, I'm glad to have found this site. My father is 62 years old and bladder cancer has been in our lives for the past 5 years. He was first diagnosed about 5 years ago with a tumor taking up 3/4 of his bladder that was pushing against his bladder walls and there was concern that it was nearly outside of the bladder. Through chemotherapy the tumor shrunk significantly, and he was able to undergo surgery and have his bladder removed, and a neobladder put in place. This past February, however, the doctors detected a large tumor in his pelvic cavity. He was diagnosed with stage 4 cancer and underwent chemotherapy again. As of his last scan, he is "cancer free", but we are all in a state of disbelief. It is great news, but seems a bit too good to be true. His doctor says that he believes in the scans, and of course insurance is not going to pay for another MRI, but I'm wondering whether this is something others would want to investigate more? We are grateful and hope the "all clear" stands, as it is the best news we could have hoped for, but it is hard to go from a frightening diagnosis to that so quickly. I guess I'm interested in hearing what next steps others would take to feel more confident/secure in the assessment. Any insight would be much appreciated. Thank you!

My response:
I've been Stage IV for more than 5 years, and cancer-free for more than 2 years. I still have CT scans every 12 weeks and expect that will continue for some time. My doctors expect my cancer to come back at some point, since BC is such a tenacious beast and "cures" are virtually unknown. So yes, keep up the the scans (CT's with contrast generally are better than MRI's for finding mets). Insurance should cover scans every 3 months, since that is the the standard of care. If your dad's cancer does come back, then immunotherapy likely would be the next therapy. It's much easier on the system than chemo, and has a better success rate. If that fails, don't despair -- there are other options. Combination therapies are now being tested and some early indications are suggesting success rates of up to 80%. Best of luck to your dad and you in the future, Ken.

Hi all, RC at MSKCC went as planned this past Saturday. Still in the hospital walking and waiting to pass gas. The good news is I receved a Neobladder which was my first choice. The very bad news is there was cancer found in one of my lymph nodes and all the rest are in pathology being analyzed. I have been told I will need chemo but haven't been told much else. I know this greatly reduces my survival chances compared to non invasive bladder cancer which I was repeatedly told was my current state. Decided to do this surgery for the "definite cure" but now looks like I did the painful surgery for nothing. Very scared and wife is devastated.

My response:
I was in the same place you were in back in May 2012. RE with neo, 12 positive nodes. Don't pay attention to the old statistics; they predate immunotherapy. Know that there are very good options available if and when your mets start to grow. Details of my journey are on my blog ( Educate yourself on the different options, including checkpoint inhibitors and combination therapies. I learned at this month's BCAN Think Tank that some new combination trials are reporting an 80% response rate. Be proactive and keep up the fight. Good luck and God bless, Ken

Mixed response to GemCarbo
 My very first post here, and I really look forward to this brave and supportive community's opinions and experiences. My mum was diagnosed with high grade bladder cancer, mets in both lungs, liver and hip and provide pelvis bones.. we only found out because of worsening pain in the hips area.. since she had radiotherapy (10 sessions), and was started on GemCarbo. After three cycles, CT showed good improvement in lungs, mets clean in liver, but her hip bone mets got worse and progressed and she now requires new radiotherapy. Has anyone had mixed response after 3 first cycles of GemCarbo?.. did you change the chemotherapy?.. or were you advised to see if bones will respond at a later stage (can bone mets respond later compared to soft tissues mets?!) Quite scared as I heard if bladder cancer didn't respond to first line treatment, prognosis is quite poor...  And words or hope or reality please!

My response:
Please look into immunotherapy. I'm stage IV and it's saved my life. Details are on my blog ( In addition, clinical trials are being tried on combination therapies of different immunotherapy and chemotherapy drugs. Some early trails have had a response rate of up to 80% -- and that's in patients that have failed first line chemotherapy. Details are in my posts regarding this month's BCAN Think Tank. If your mom is not at an NCI Center, please have her go there. Good luck and God bless, Ken

My husband is scheduled to have his bladder removed next month. After having scopes followed by BCG treatments afterwards, that stubborn cancer has come back, always as carcinoma not an actual attached tumor with penetration to the wall. Because this has gone on for almost 2 yrs. every Dr. we have been to says to remove the bladder. The cancer has made it into the uretha past the prostate, it'll all need to go. Dr. doesn't know if he will be eligible for the neobladder, which is what we were cautiously hoping for. Being a diesel/heavy equipment mechanic, doing this type of work with an external bag sounds difficult. Although we have heard negatives about the neo. also, such as it is only successful for 5 yrs or less and you can't lift heavy objects or it can rupture or there are many more complications because of it. We have to let the Dr. know if we want to go that route prior to surgery even though the Dr won't know if he can do it until the surgery is underway. We aren't sure of anything anymore. He just turned 60 and can't afford to retire w/o SocSec and Medi-care. Any info would be helpful.

My response:
Remember that the point of the bladder removal is stop the cancer. You're asking questions about the side effects of the therapy, which is like worrying about the tail instead of the dog. When I had my RC at age 49, I worried about that more than the cancer. But tens of thousands of people have done just fine with all of the diversions. All involve an adjustment, but it's not as big of a deal as it appears to be. The important think is that your doctor gets clear margins and the cancer is gone.

As it turned out, my cancer had spread to my nodes (12 positive), so I've been Stage IV for more than 5 years. I played cancer whack-a-mole for several years until I got into an immunotherapy clinical trial and was fortunate enough to have a complete response. Details are on my blog at if you think of your husband's cancer as a chronic disease to be managed instead of an acute phase, it will help you realize you're in a marathon, not a sprint. And as a caregiver, you need to ensure that you're taking care of yourself, too. Get a strong support system around you This forum and BCAN support groups can help. Good luck and God bless, Ken.

I'm having my first CT Urogram tomorrow and I'm told that I'll be drinking contrast an hour before test. I see a lot about IV contrast but not drinking it. Is drinking as good as IV?

My response:
I've had more than two dozen CT scans in my nearly 6 year journey with mets BC. All involved IV contrast; about half also had me drink beforehand. The drink has a radioactive isotope, usually barium, that helps the CT scan get a much better imagery of your gut. The IV contrast is transmitted through your bloodstream and doesn't allow the gut to be viewed as well. Both types of contrast tax the kidneys, so it's important to drink several liters of Diet Coke or other fluid of your choice after each scan. If you have concerns about drinking the contrast, speak to your doctor or radiologist well BEFORE you have the scan. If you choose to not drink the contrast, the scan likely will still proceed, but the imagery won't be as good.

Dr Bivalacqua performed the RC yesterday morning 9/11/17. 4.5 hour surgery. He said everything went perfect. Bladder out, neobladder in. It feels like I've done 1000 sit-ups. Ugh! They have not allowed me to walk yet since my blood pressure is low and they are afraid I could pass out. Bummer? I feel pretty good though. Now the fun begins.  

My response:
Here's to hoping you pass gas soon! My written neo recovery instructions said to avoid roughage like lettuce or high fiber foods, and to eat easy to digest foods like cake and pies. That was in May 2012 and no one ever told me to stop following doctor's orders, and I'm doing my best to comply! Good luck and God bless, Ken

Saturday, August 12, 2017

Spencer's finished the AT!

August 12, 2017
Today my son finished his thru-hike of the Appalachian Trail. He departed from Springer Mountain Georgia on March 11. Five months and one day later, he arrived on Mt. Katahdin in Maine. What an accomplishment!

Spencer dedicated his hike to the memory of his best friend, Chris Atwood, who died of a heroin overdose five years ago at age 21. Spencer's goal was to raise $21,000 for the Chris Atwood Foundation, which was founded to help prevent opiod addiction and to distribute nalaxone as needed. He's almost there - you can help him reach his goal by donating at

Saturday, August 5, 2017

Notes from BCAN Think Tank day 3

2017 BCAN Think Tank Day 3

The day started with presentations by BCAN’s recipients of its young investigator awards: “Identifying Genomic Determinants of Chemoradiotherapy Response in Muscle-Invasive Bladder Cancer.” Kent Mouw, MD, PhD, Dana-Farber Cancer Institute, and “Role of antigen-specific immunity in BCG therapy for bladder cancer.” Niannian Ji, PhD, University of Texas Health San Antonio. These were followed by presentations by the 2017 John Quale Travel Fellows. These awards set BCAN apart from many other patient-founded cancer advocacy organizations, because they are targets to get more researchers involved in finding new therapies for bladder cancer.  

Breakout groups followed. There were a several that were of interest to me: the survivor’s working group intended to focus research on patient-centered outcomes; the presentation on restoring and enhancing sexual function after RC, chemotherapy, and other treatments for bladder cancer; a discussion of bringing precision medicine to bladder cancer therapy; and the session that Jennifer opted for, Unmet Educational and Psychosocial Needs across the Bladder Cancer Continuum. But I ended up attending the session on Novel Immuno-Combinations. The summary promised the following:

Antibodies targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) axis have known therapeutic activity in patients with metastatic bladder cancer. However, only a 15-25% of patients will derive clinical benefit when treated with single agent therapy. Therefore, there is an urgent need to design optimal combinations to improve patient outcomes. Discussion highlights combination approaches to improve outcomes to front-line immunotherapy regimens as well as overcome acquired mechanisms of resistance to immune checkpoint blockade.  We will provide an overview of emerging preclinical data and contextualize the current clinical trial landscape of immunocombinations in urothelial cancer.

I figured that I should learn more about what therapy options were out there if and when my current remission failed and my cancer resumed its attempt to kill me. Along those lines, Dr. Andrea Apolo told me earlier in this conference that she had just opened a three drug trial with cabo, nivo and ipi, and that it looks promising. Maybe that's for me in the future.

Dr. Hahn introduced the session with a slide how 5 new immunotherapy drugs had been approved for mets BC in the past year, and more were in the pipeline. The challenge is how we select the appropriate drug for treatment. Chemotherapy works. But we’ve got an “embarrassment of riches” of therapies and targets. His slide had 55 different targets. If we were to do a 20 patient test for each one, that’s more than 1000 patients and years of data. It’s going to be a challenge to better design trials for efficacy and translational data.

Panelist # 1: Dr. Chris Hoimes explained how the different responses of patients was based upon spatial and temporal tumor heterogeneity. A patient with resistant subclones will be less likely to respond to therapy. Patients with high tumor heterogeneity has a much higher chance of dying sooner. (Lilu et al, Abs 4512, ASCO 2017). Post-treatment genomic alterations can enable those to become the dominant clone. Paradoxically, tumors with a higher baseline mutuation or noeantigen burden experienced a greater decrease with GmeCis (Lilu et al, Abs 4518, ASCO 2016). These data can help guide our decisions on future treatment decisions.

Drawing from studies of chemo+immunotherapy in lung and breast cancers, we can deduce that such combinations may be more effective for BC patients. In May 2017, FDA approved a combination of Pembrolizumab with chemo for mets Lung cancer. We don’t know exactly why this appears to work. A large phase III trial is underway. For breast cancer, the I-SPY2 study showed that patients that got combination of pembro and paclitaxel, then AC chemo, then surgery. Even triple negative patients were having good response rates. Side effects were manageable.

Urothelial cancer combination drug studies are underway, including GemCis chemo with ipi, pembro, atezo, and other immunotherapy drugs. We need more patients and await the data.

What is the rationale for combination therapy of chemo with immunotherapy? Chemo can induce immunogenic cell death, and immunotherapy can enhance tumor control. The two together can have a synergistic effect. Cisplatin may not bring around immunogenic cell death (ICD), but instead bring TCD. We’re rather see ICD than TCD.

The tumor microenvironment and metabolism considerations tell us that lower pH in the tumor interferes with the reproduction.

Conclusion: chemo and immunotherapy might be an attractive option for bladder cancer, either as neoadjuvant or adjuvant. There might even be a role for this combination in NMIBC. (See slide 16). The variables (slide 17) need to be better understood. For example, the timing – chemo first , or immunotherapy first, or concurrent? MSKCC is looking at that. Also to be determined is whether to give the full dose, or less than the full dose of chemo. Additional concerns (slide 18) are that steroids are usually given with cisplatin, but steroids don’t pay well with immunotherapy. 
Challenge #1: How does anyone actually survive MIBC? Neoadjuvant chemo followed by surgery provides the best odds for survival. But why are there differences/ We need to better understand clonal divergence and evolutionary pressures.

Challenge #2: No nodal disease at RC, but it shows up months later. (Markowitz Science 2017, Nxerova et al, Science 2017). This reflects changes in the tumor genomic landscape post-therapy.

Challenge #3: Mets with a transient response to therapy likely reflects tumor repair mechanisms. Identifying these omic changes should reveal why this is happening.

Tumors in “deep remission” still need to be followed and understood.

Panelist #2: Dr. Charles Drake, Columbia. Pathways and possibilities for immunotherapy. PD-1/PD-L1; CTLA-4; agonist antibodies; and metabolic and TME targets (IDO+A2A), and MANA from heaven – personalize vaccines? (non-personalized vaccines have been mostly unsuccessful).

When an antigen meets a tumor, the CD8T expresses PD-1. When that happens, the CD8 T cell expresses interferon, and that kills the tumor. We’re getting a better understanding of why that doesn’t work. You need to have ongoing antigen presentation for checkpoint inhibitors to work. With no antigens present at the tumor, immunotherapy will not work.

CTLA-4 (ipi and others) can help, but it has significant adverse events. We’re studying how to make CTLA-4 more tolerable in mouse models. A depleting antibody is one idea. The idea is a combined checkpoint blockage. For example, both anti-PD1 and an LAG-3 have an 80% response rate in mice.

The second idea is using immune agonist antibodies. OX40 works in mice, but not in humans. Why? We’re working on that. There are lessons that can be applied, but I don’t understand all of the technical details. Likewise for IDO pathways.

Panelist #3: Immune-Targeted Combinations, by Prof. Bart Cowles. Ipi plus nivo isn’t significantly better than nivo alone. But both are better than ipi alone. Other immunotherapy drug combinations likewise have been mixed. We’re not seeing the spectacular results we’d like to see. But the data is still early and young, and there are lots of exciting things to study. But let’s not get ahead of ourselves. We still have not properly tested immunotherapy combinations in bladder cancer. We know that BC is molecularly heterogeneous disease, and harder to find effective agents. The triple trial of cabo with nivo and ipi looks promising. Also promising is BISCAY for MIBC (four arms Durv+AZD4547; Durva+AZD8186; Durva+Lynparza; Durva+AZD1775). A targeted triplet therapy for mets BC with chemo and two immunotherapy drugs. It sounds “bat-shit crazy”, but it’s not.

Panelist #4: Dr. Naidoo, epigenetic therapy and immunotherapy. We’ve seen this tried with lung cancer, and it has shown better results than monotherapy. But it’s not a home run. There is a theory for epigenetic priming before immunotherapy. Sometimes it appears to work. Further studies are underway.

Combination studies with nivolumab are also underway in NSCLC’s. They appear to have better results. We need to move those studies into the BC realm.

Afternoon session:

Future Targets and Therapeutic Approaches–Beyond Immunotherapy, Matt Galsky, MD, Mount Sinai Hospital. Three new drugs are being tested.

1) Enfortumab Vedotin is having a very promising response. Response rate are in the 40-60%. This is a heavily pretreated population. There is a fairly robust response for patients with liver mets, which is a hard mets to reach. It’s a quite active agent. Patients have also had reductions in bone mets. These are areas that we don’t see activity in with most other drugs. We’ve sen steep reduction in bone pain in some patients. When it works, it’s really working well. ORR is 53%. Phase II study is planned. There is also a Phase Ib study with immunotherapy.

2) ADG-15ME. Small studies have a 50% response rate. Phase II studies are planned. The manufacturer may be shutting down, so we’re not sure of longer-term availability.

3) Sacituzumab Govitecan (IMMU-132) is a pan-epithelial antibody that reaches across tumor types. Small studies have suggested promise, with an ORR of 50%. Updated data will be presented at ESMO 2017.

These antibody-drug conjugates are a type of chemo-lite. They have promising second line responses. The question everyone is asking is whether these drugs can be combined with immunotherapy. We’re testing that. We also need to learn how to use them – dose frequency, total number of doses, etc.

Peter H. O’Donnell, MD, University of Chicago Medicine. Targeting angiogenesis. History: 1985 was the first year that MVAC was reported to work on urothelial cancer. 2012 was the first year immunotherapy was reported to work in urothelial cancer. The 30 intervening years was mainly spent rearranging cytotoxic deck chairs on the Titanic. We don’t want to say that about immunotherapy in 30 years. Focusing on three targets:

ERBB2 (HER2). Breast cancer has been looking at HER2 for some time. Relatively few breast cancer patients have this mutation. By contrast, the majority of BC patients have this mutation. It’s an area that has the potential for a large benefit. Afatinib has been studied in for ERBB receptors in a phase II study. 5/6 of the patients with HER2 achieved PFS3 endpoint – they had genomic alterations, and lived longer as a result. (Choudhury et al, JHO 2016). Measuring HER2 amplification by IHC or FISH may not be determinative in response, but it is suggestive. 3+ patients response better, but 2+ patients results are mixed. So we’re seeing some promising results in HER2 therapy. Micropapillary might be especially promising. We’re trying to recruit additional patients (and institutions) for our study. The Afatunib drug needs close management since it has so many toxicities.

FGFR3. Has shown promise for advanced mets patients. 5 of 8 patients saw long-term reduction of tumor burden. Some patients have seen prolonged responses. The data is similar to immunotherapy. Janssen is bringing this drug forward for BC.

ERBB3 (HER3). We’ve also seen promising response in small studies relating to ERBB2.

Targeting angiogenesis, Arjun Balar, MD, New York University Langone Cancer Center. Sunitinib has been tested is several studies. Waterfall plots showed there is was modest response. We looked at combination studies with chemo an saw that there might be a higher response rate, but these were small phase I studies. Lilly has a positive result in the RANGE study using Cyramza.

Unanswered questions for immunotherapy: 5 drugs have been approved for second line therapy; two for first line for chemo ineligible therapy. But a minority of our patients respond. We need to do better.

Studies show that a higher VEGF level can inhibit tumor growth. Maybe we can combine VEGF blockages with immunotherapy. A phase I study combined atezo and bevacizumab was well-tolerated, had evidence of synergy, and had good responses in 4/10 patients. Beva appears to be working in the small molecular compartment. We’re preparing a Phase II of atezo+beva vs. atezo alone. Other studies have been done (e.g., Apolo et al, using cabo, ipi, nivo), and axtinib+pembro showing up to a 70% durable ORR; a phase 3 is pending.

Targeting tumor metabolism, Ubaldo Martinez-Outschoorn, MD, Thomas Jefferson University. The Warburg effect shows that the main metabolites for cancer is pyruvate. It’s an inefficient process. Why is cancer using such an inefficient process to generate ATP? There is altered tumor vascularization and relative failure of antiangiogenic therapy. Think of tumors like coral reefs – both can thrive in poor environmental conditions.

Friday, August 4, 2017

Notes from BCAN Think Tank Day 2

2017 BCAN Think Tank Day 2

Engaging Patients in Research, presented by Angie Smith, Assistant Professor, UNC Chapel Hill.

“Patient engagement is the blockbuster drug of the century.” Three objectives: Patient centered outcomes and its interaction with patient engagement; types of patient research; and future plans.

Patients want to know the benefits and harms of research; how it’s going to affect their lives; stakeholder perspective.

Patient engagement is necessary in a meaningful way throughout the research. They are not lab mice.

Prep phase: select questions that have meaning to the patients. The execution phase (randomized or not) can affect recruitment, data collection, and analysis of results.

Translational: disseminating the results – can benefit by using the patients to publicize the results and better ensure that that the study is used.

Groups like this – including patient advocates – help guide the proper research questions. BCAN’s patient survey network helped prioritize the studies. Step 1: recruit patients and caregivers to join the patient survey network. There are more than 26,000 in in BCAN Inspire community. Step 2: Generate and prioritize the research questions from the surveys, then narrow them down to 3-5 per disease stage. Researchers should listen to patient stories and turn them into questions. Step 3: Survey sent to BCAN to validate our process. We did that in two different years and got three times the participation on the second time. Step 4: Disseminate the research questions to universities, BCAN, funding agencies.

Prorities: PCORI 2017 put NMIBC on the chart for priorities for the first time. PCORI disseminates $1.6 billion in funding.

Future: continues PSN growth; bi-annual research prioritization; patient empowerment through education. PEER: Patient Empowerment through Engagement Research has been funded for several years, getting patients on research teams.

As health care providers, we need to hear about what research questions are important to the patients, and have that guide our efforts.

Save the date: BCAN Leadership Summit: Washington DC, Oct. 13-14.

Renate Louwers, BCAN Patient Advocate

Renate lost her husband to bladder cancer in 2014. She’s a voice for metastatic bladder cancer patients and caregivers. Patient forums such as provide a lifeline to patients. They are willing to provide the “soft skills” that are so helpful. Researchers should consider reaching out to those communities.

Implementing Patient Reported Outcomes (PROs) into Clinical Practice, by Dr. Ben Brooke, a vascular surgeon at University of Utah. Sometimes the medical team is happy and the patient feels poorly. The model for measuring quality of healthcare – Access, Structure, Purposes of Care to clinical outcomes and patient experience. The patient experience is being factored into Medicare reimbursements. It’s important to know. PROs are and report of a patient’s health states that comes directly from a patient without interpretations of the patient’s response by a clinical or anyone else.

So how do clinicians make PRO outcomes more useful to us? PROMIS: Online repository of validated instruments to measure assessment of patient status. Lots of different measures. Why use it? It provides standardized measurements across different domains and diseases. IT’s “cross-walked” to other measurement. They are reliable and valid. They are inclusive, and flexible and efficient. CAT (computerized adapted testing) changes the subsequent questions based upon the prior responses. That helps make it more user-friendly.  

Health Information Technology (HIT) lets patients provide information on their own computers or phones. Some institutions hand each patient an iPad with their data on it, and also surveys, and additional information. The measures are real-time loaded into a patient’s EHR (Epic) and can be reviewed by the clinician. It can be customized based upon PROMIS factors to meet the patient’s needs. It takes less than 4 minutes average to complete the entire analysis.

Data shows that mets cancer patients who receive automated PRO assessment had a better outcome, including greater long-term survival. (JAMA 2017). PRO for bladder cancer exist and could be implemented by your practices. The BCI – bladder cancer index – can provide better tracking of patient outcomes.

Patient-Reported Outcomes: Sharing Data Across Healthcare Systems, by Danielle Lavallee, U Washington. PROs are increasingly common, but there are issues in translating it across different healthcare systems. Insurance companies are requiring this. It’s complex. Knowing what to measure and how to measure is important – before the medical intervention and up to 2 years after the intervention.

Too often, electronic health records don’t link up to each other. There are tools available to now do that, and make the data available in real time. Clinicians can use dashboards that pare down how their patients are doing. It also helps aggregate data and see how institutions are doing. The ability to compare outcomes needs to take into account the patient data and improve the care. “Systemness” for PROs is the goal – to use the data to help improve every aspect of the system. There are diverse needs to measure for patient, provider, system, and reimbursement. Each of the metrics exist, but there are slight differences. Knowing how to capture and apply this data is critical. Example: level of alcohol abuse may not be documented in charts, but relevant to a surgeon.

Multiple stakeholder themes: workflow; IT systems; reduce the burden (keep it under 5 minutes), etc. There are lots of challenges: policy vs. practice; research vs. routine care; how to capture the data and how it changes the workflow; Electronic Health Records (EHR’s) are not patient centered or integrated across organizations.

Opportunities: It’s still early. The environment is changing quickly. Dynamic environment. Unified stakeholder needs. Collaboration to support success: clinics, social workers, etc. The value of PROs for health care increases as we increase the ability to compare outcomes.

Breakout groups

I attended the Survivors Working Group. We zeroed in on three topics to work on over the next year:

1.      Update and enhance information in BCAN Support and Discussion Groups

2.     Improving patient access to understanding clinical trial options. BCAN’s clinical trial dashboard can be improved by helping sift through the options.

3.     Travel guides for traveling with ostomy pouches, preparing a summary of information from reputable sources. TSA information is available here and here

SWG members will self-select and join the working groups that are of interest, pick your leaders, set your agenda.

In the afternoon, Bob, Marge, Nancy, Jennifer and I ducked out of the main session and conferred about revamping the BCAN Volunteer and Resource Guide, and internal guide provided to patients and caregivers who agree to take phone calls from people who call into BCAN seeking guidance.