MD Anderson Houston - 011

Mike and I flew to Houston to meet with an oncologist at the “University of Texas M.D. Anderson Cancer Center” (MD Anderson Houston) who specializes in prostate cancer. MD Anderson Houston is a world-renown comprehensive cancer center and the largest of its kind in the United States. “U.S. News and World Report” ranks it the number one cancer treatment center in the nation and ranks it number six in urology. It is also considered a prostate cancer center of excellence.

My oldest brother, Matt, is also a physician and happens to know one of the oncologists at MD Anderson Houston who specializes in prostate cancer. Matt put us in touch, and I immediately scheduled an appointment.

I can’t emphasize enough how important it is for any man diagnosed with advanced prostate cancer to get a consultation with a physician at a prostate cancer center of excellence. Even if you trust your local doctor and feel like they know what they are doing, I feel it is imperative to have a second or third opinion with a doctor at these types of specialized cancer centers.

This is because advanced prostate cancer is considered incurable, difficult to treat properly, and is an extremely heterogenous type of cancer. By heterogenous, I mean tumor types are highly variable from patient to patient and you can have different prostate cancer tumor types in the same individual. Research and treatments of advanced prostate cancer are rapidly evolving, and guidelines can change from month to month depending on the results of the latest clinical trials.

The physicians at these prostate cancer centers of excellence are well-versed on the latest treatment and should be aware of, or at least able to look up all of the clinical trials in the United States, for which you might be eligible. These centers of excellence have multidisciplinary teams who work together to provide the best possible care you can get in the United States (U.S). For example, a multidisciplinary team may consist of a surgeon, geneticist, oncologist, radiation oncologist, and various other healthcare providers who work together to optimize your care.

Based on my experience, many physicians who specialize in prostate cancer, but who aren’t associated with a prostate cancer center of excellence, are not well-versed in the latest research or the rapidly evolving treatment options. Many of them have no idea about the importance of genetic studies to assess for inherited (germline) genes and tumor (somatic) genes in advanced prostate cancer.

Many of these physicians don’t know that, for example, the BRCA2 gene mutation, may be absent in your germline but present in your tumor tissue. Studies show that having BRCA2, especially if biallelic (present in both copies of a gene), may make men with advanced prostate cancer responsive to immunotherapy with drugs called poly(ADP)-ribose polymerase (PARP) inhibitors. While these types of genetic mutations are relatively rare, you won’t know you have them unless your physician tests for them. There are several clinical trials using PARP inhibitor drugs in men with these types of germline and somatic tumor mutations.

Mike and I took the hotel transportation van to the massive MD Anderson Houston campus. It took us into a garage whose building entry resembled a high-quality hotel with multiple lanes and service agents. I had printed out my instructions on what to do once we arrived and we proceeded upstairs to get checked in. While I went off to get checked in, an old and dear friend from high school walked up to Mike in the hallway and asked if he was Michael, Keith’s husband. He was very surprised and said he was. She introduced herself to Mike and told him she and her husband would be in the patient waiting area.

When I got back from checking in, Mike and I went to the waiting area, and there were two of my friends from high school. They were married, he had prostate cancer, and his doctor was the same one I was seeing that day. I already knew he had the same doctor but I had no idea they were going to be there the same day I was. So here was yet another high school classmate of mine with prostate cancer. But in this case, his prostate cancer was advanced like mine.

It was a mixed blessing seeing them both. I couldn’t remember the last time I had seen them though we stayed in touch on Facebook. I immediately walked over to them and gave them both a big hug. Seeing them brought back a lot of really good memories, but my heart hurt for them as I hugged them. Even writing about them now makes me tear up. I know the suffering they are going through. As I hugged him, I said, “I’m so sorry you are going through this.” We sat and talked until it was time for my appointment. They stay in my prayers and I love them both.

My name was called and Mike and I were escorted into a patient exam room. First, the urology fellow came in and performed a history and physical. A while later, the oncologist, his nurse, and the fellow entered the room. The oncologist was very kind but looked tired. The kind of “tired” you see in people who carry an unimaginable level of responsibility and work really hard. Can you imagine being an oncologist in a world-renown cancer center? People come from all over the world to see you, many of them extremely sick, most of whom are incurable, yet many expect you to cure them.

This oncologist is very involved in clinical trials, specifically trials using immunotherapy to treat advanced prostate cancer. We discussed the clinical trial I had found involving the PARP inhibitor, rucaparib, to treat castrate-sensitive men not taking ADT. He agreed that testing the tumor tissue for somatic mutations was a good idea. This is because certain gene mutations were part of the inclusion criteria to even be considered for that clinical trial.

And because I was intolerant of ADT, this clinical trial might be my best bet for effective treatment without the use of ADT. He told me, at that time, all of the clinical trials for advanced prostate cancer being done at MD Anderson Houston involved only castrate-resistant prostate cancer patients. Meaning that all of those men had progression of their cancer while being on ADT.

Ironically, in many of those castrate-resistant patients, the progression was caused by the ADT drugs mutating the cancer into a more resistant and aggressive form. Practitioners who treat advanced prostate cancer will rarely tell you that fact. They just present it as the tumor outsmarting the drugs used to lower or block testosterone, when in fact, mutating to more aggressive prostate cancer, in many instances, is a direct result of the ADT drugs causing molecular changes at the cellular level.

This is partially why advanced prostate cancer is considered incurable. The drugs used to treat it suppress testosterone. In turn, low testosterone levels cause these prostate cancer cells to make molecular changes that mutate the tumor into more aggressive types, which eventually results in death.    

The patient onboarding process at MDA Houston is so thorough that they had already requested and received the tissue from my prostatectomy. That meant they would be able to order the somatic gene mutation testing of the tumor tissue through a company called “Foundation Medicine,” a company pioneering genetic testing in cancer. In comparison, Baptist MD Anderson Jacksonville wasn’t even sure if they would be able to get my insurance to cover the genetic testing.

I discussed with the oncologist my interest in prostate-specific membrane antigen (PSMA) theranostics, which involves a diagnostic PSMA PET scan looking for the antigen, a protein, on the cell surface. If the PSMA PET lights up and shows the antigen is present on the tumor cells, then you can treat it with PSMA radioligand therapy (PRLT).

PRLT involves injecting a radioisotope that attaches to the antigen on the tumor’s cell surface and releases a two-millimeter burst of radioactivity. It’s a precision type of radiation that tends to spare healthy cells. PRLT has been used in Germany for the past ten years and in Australia for the past five years. It’s just now being used in the U.S. but only in clinical trials, none of which I’m a candidate for because I’m not castrate-resistant.

By now you should be starting to see a trend in clinical trials in the U.S. for advanced prostate cancer. The majority require you to be castrate-resistant, meaning you had to have been on ADT long enough to become resistant to ADT. At the time of my appointment at MD Anderson Houston, there was a clinical trial in progress called the “VISION” trial, which was investigating the use of PRLT in heavily pretreated men that were progressing despite ADT. All of these men had also been treated with chemotherapy.

There is clinical evidence coming out of Germany that shows men with castrate-resistant prostate cancer who have been previously treated with chemotherapy, don’t have as good a response to PRLT as others not treated with chemotherapy. My theory is that some men who have been treated with chemotherapy are the sickest of the sick and that pretreatment with chemotherapy only further weakens the patient and prevents PRLT from working well. I will dedicate a future newsletter to PSMA theranostics.

At the time of my appointment with MD Anderson Houston, there were several cancer centers in the U.S. involved in the “VISION” trial, and these centers had been granted FDA approval to use PSMA PET scanning in clinical trials. But because the FDA had not granted approval of the PSMA PET scan outside of clinical trials, I would have to pay cash for the PSMA PET scan.     

The oncologist downplayed my idea of potential involvement in PSMA radioligand therapy (PRLT)saying that even if the therapy got my PSA down to zero, not all of my cancer cells make PSMA. So, what would happen is that all of my cancer cells expressing PSMA would die, but that I would still be left with “the same dilemma,” meaning PRLT would not get all of the cancer cells, and I would remain incurable. Ironically, this scenario plays out in every current treatment strategy for advanced prostate cancer, including those involving ADT, which I cannot tolerate. So why downplay the idea of me potentially receiving PRLT?

He also acknowledged that treatment with an immunotherapy drug would only buy me some time. In other words, neither PRLT nor immunotherapy is curing advanced prostate cancer, only buying you time. And that’s the major issue with therapies for advanced prostate cancer. Unless you are an exquisite outlier or your cancer spontaneously regresses, you probably won’t be cured.

Then he went on to say, “We are not curing everyone.” We are curing a small percentage.” I was surprised he used the word “cure” when discussing advanced prostate cancer and I didn’t press him on what he meant by that. I assumed he was talking about the rare patients who go into “durable remission” with therapies. These types of patients are called living outliers, which means they are exhibiting unexplained prolonged survival given their diagnosis of incurable prostate cancer.

I think the major reason he downplayed the idea of PRLT is that it’s fairly new to the U.S., and at that time, no clinical trials in the U.S. had shown PRLT produced an increase in overall survival. In addition, MD Anderson Houston was not involved in the “VISION” trial, so I’m pretty sure he didn’t want to advocate for PRLT based on those two main factors.

Another issue, which he didn’t seem to be aware of is that Dr. Richard Baum in Germany is showing that in certain individuals with advanced prostate cancer, PRLT can be used as maintenance therapy. In other words, PRLT can be given over and over as needed for recurrence of the tumor with relatively few side effects compared to ADT and immunotherapy.  

He did say that I was an “ideal patient” in that I was young and in great shape. The downside was my inability to tolerate hormone therapy, which is a foundation treatment in advanced prostate cancer. Then he said, “We just need you to tolerate this for a little bit.” He didn’t clarify that last statement and I didn’t ask, but what I assume he meant was that I needed to be on ADT to be eligible for other advanced prostate cancer clinical trials.

Therein lies the catch-22, “a problem for which the only solution is denied by a circumstance inherent in the problem..." ( catch-22, Merriam-Webster. Retrieved July 15, 2021) Theoretically, the solution is therapy (ADT) that provides for a durable remission, or a cure, is denied by the fact that ADT creates pressures in the cancer cells to make them more resistant and more aggressive.

When I brought the rucaparib trial for castrate-sensitive prostate cancer patients to his attention, he shifted gears and made more information-gathering part of his initial plan. This included testing the prostate tumor tissue from my prostatectomy for genetic mutations to see if I had any of the mutations that would make me eligible for that rucaparib trial based in Salt Lake City, Utah.

Even though MD Anderson was not participating in that clinical trial, he felt like it was my best shot for getting into an immunotherapy study for prostate cancer given I was castrate-sensitive and not on ADT. My ticket into this trial would lie in the genetic testing, which needed to be performed on my tumor tissue.

He went on to discuss his second therapeutic plan should the genetic testing of my tumor tissue not make me eligible for the rucaparib trial. This plan involved starting a drug called dutasteride, brand name Avodart. Dutasteride is FDA approved to treat benign prostatic hypertrophy, an enlarged prostate, and male pattern baldness. It works by blocking the conversion of testosterone to its more potent form called dihydrotestosterone. It’s also used “off-label” to help prevent prostate cancer. I also found a clinical trial that showed, over a three-year period, dutasteride prevented the progression of early-stage prostate cancer while under a period of watchful waiting after a prostate biopsy.

He recommended I first start dutasteride to make sure I tolerated it, then add the same drug the urologist at MD Anderson Jacksonville recommended – bicalutamide, brand name Casodex. Bicalutamide is an androgen receptor antagonist, meaning it blocks the receptor that binds testosterone and dihydrotestosterone. This differs from the ADT I received by injection, which helped lower the production of testosterone instead of blocking it at its receptor.

His idea was that I might tolerate that combination of dutasteride and bicalutamide better than I tolerated the injectable form of ADT. In addition, he mentioned I might consider trying venlafaxine, brand name Effexor, an antidepressant, that has been shown to help reduce hot flashes caused by ADT in about 25-40% of prostate cancer patients. He didn’t recommend venlafaxine to address the depression caused by ADT because it has never been studied in men whose depression was caused by ADT. He knows the data just isn’t available to make any specific recommendations regarding treating depression caused by ADT.

He also briefly mentioned other drugs to consider including enzalutamide and apalutamide, which he categorized as second-generation anti-androgen drugs after bicalutamide.

He went on to say that if I tolerated venlafaxine, dutasteride, and bicalutamide, he would then like for me to switch back to an injectable ADT, specifically recommending Lupron. Lupron is a drug with the same mechanism of action as Trelstar, the injectable ADT drug that gave me such horrible side effects.

The plan would be to start on a “baby dose” of Lupron, meaning a one-month long-acting injection versus three months or six months long-acting injection. The one and only time I tried injectable ADT with disastrous results was with a “baby dose” or one-month long-acting form.

Then he mentioned that if venlafaxine wasn’t effective in alleviating hot flashes caused by the ADT, I should consider using gabapentin, brand name Neurontin, an anticonvulsant, which is also shown in clinical studies to help reduce hot flashes caused by ADT. You can read the very long list of side effects of gabapentin for yourself if you are interested, many of which my patients complained about when I prescribed it for other indications.

He was hoping to segue me back into ADT via the use of venlafaxine. Now I must admit that this was the first physician in my prostate cancer journey to have come up with such a well-thought-out plan of attempting to ease me back into ADT. I should have known he would be the one to think “out of the box” since he is considered one of MD Anderson Houston’s gurus in prostate cancer care.

This is why I can’t emphasize enough the importance of getting a consultation with a prostate cancer specialist at one of the prostate cancer centers of excellence. The physicians at these centers see some of the most difficult patients, keep up with the scientific literature, are super smart, and are innovative in their approach to cancer care.

I was impressed with his recommendations, but I had already decided I was not going back on ADT. Besides the horrible quality of life I’d experienced on it, I had also done the research and found that 99.9% of hormone-sensitive prostate cancer patients go on to develop mutations of their cancer cells, many of which are acquired. By acquired, I mean that the mutations are directly induced by the androgen receptor axis blockers including the oral and injectable forms, as well as the first- and second-generation drugs he had named.

Then I posed the same question to him that I’ve posed to all the other prostate cancer physicians.

“Can you help me understand why after almost eighty years, we are using androgen deprivation as first-line therapy when the research shows that it causes these acquired genetic mutations and turns them into highly aggressive tumors, including the very deadly neuroendocrine type tumors? Why aren’t we studying more immunotherapy drugs and PARP inhibitor drugs earlier in the castrate-sensitive setting before your body is overwhelmed with metastases and has had your immune system severely compromised by chemotherapy? It seems like we’re not using a common-sense approach here with advanced prostate cancer.”

His response was “Yeah, that’s a great question.” Then he went on to say, “So it’s because there are very few drugs that seventy-five percent of men respond to and respond well. Even chemotherapy doesn’t give you that response rate.” He then went on to explain that pharmaceutical companies are running clinical trials for prostate cancer because they have billions of dollars to do so.

He used the example of abiraterone acetate (AA), brand name Zytiga, saying this drug first came into awareness in the late 1990s. He said at that time, the only way drugs were approved for prostate cancer was if they impacted overall survival. He opined that when you are looking at overall survival and “time is of the essence,” pharmaceutical companies are going to create clinical trials involving the sickest patients. And they do this because the time frames they choose will need to happen rather quickly with these sickest patients, therefore; clinical trial results will generally be published within one to two years in this patient population.

He said that at the time researchers began studying AA, the only other drug available to treat metastatic castrate-resistant prostate cancer (mCRPC), outside of first-generation anti-androgens, was the chemotherapy agent docetaxel. Researchers found that AA was effective in these mCRPC patients previously treated with docetaxel, and then decided to do clinical trials with AA in mCRPC patients not previously treated with docetaxel and they “got a win there.”

So then researchers asked themselves, “Can we successfully use AA even earlier?” Then they designed a clinical trial for men with metastatic castrate-sensitive prostate cancer (mCSPC), meaning in patients with metastatic prostate cancer who had never been treated with ADT. In that clinical trial, they combined AA with ADT to see if they could maximize overall survival in this group of men, “and that trial won.” He bottom-lined it by saying because the pharmaceutical companies are making money off of their earlier successes in men with very advanced disease, they can then design more clinical trials for prostate cancer patients with earlier disease.

My response to him was that the seventy-five percent success rate he mentioned isn’t truly a success because you are using ADT drugs that are actively creating mutations, which will ultimately result in resistance to these drugs, including the second-generation anti-androgens.

I asked why researchers aren’t doing genomic testing on newly diagnosed prostate cancer patients and using immunotherapy with the ones who have actionable germline or somatic mutations. His response was that he knew of a group of researchers in Vancouver germline testing men with localized prostate cancer with the intent to treat some of them with actionable germline mutations.

Since this appointment at MD Anderson Houston in July 2019, several clinical trials for early prostate cancer have popped up using germline and somatic tumor mutations as inclusion criteria for entering their clinical trial.

Before we ended our appointment, he was kind enough to offer his assistance in getting me set up for PSMA testing. He offered to make a phone call to physicians at UCLA where they were studying PSMA PET scanning and help set up my referral.    

At the end of our appointment, he made a statement that was very telling. He said,

“You are part of the MD Anderson family, and when I say that, not that Jacksonville is MD Anderson. I mean it’s not like you have people like me training and going there. It’s sort of like Trump. Sorry I hate to use that as an example.”

Then I said, “I understand Jacksonville is licensing the name like Trump licenses his name. My experience at MD Anderson Jacksonville showed me it doesn’t come close to what MD Anderson Houston has to offer as far as the same level of high-quality care.”  

He kindly ended our meeting by saying he would be happy to take over my care but understands Houston is far for me to travel. The last words he said to me were, “When I take over, I’m a control freak.” I know what those words mean because I’m a recovering control freak. It means were he to take over and direct my care, it would be “his way or the highway.”

Given my unique circumstances of being diagnosed with incurable cancer and being intolerant of the primary pharmaceutical treatment options, I didn’t feel comfortable giving anyone complete control of treatment decision-making no matter how qualified they may be. That’s because, from this point forward, every decision I make regarding the treatment of my cancer involves a delicate balancing of my quality of life with the prolonging of my life.

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As a physician who understands my prognosis and the therapies available for advanced prostate cancer, I’ll remain open to suggestions for therapies, but I won’t let another physician call all of the shots. No other person could ever understand my unique experience on ADT and no other person will be the decider of my quality of life.

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Some may say that I’m being selfish by denying therapy that could prolong my life; that I’m not taking into consideration my loved ones. Thankfully, I don’t have children and my husband is fully on board with the decisions I make regarding this cancer. As far as my friends and other family members, I don’t think they would be selfish enough to insist I choose a poor quality of life over living longer. That argument would be different if the treatment options could potentially cure me, but no study has shown that any treatment option available at this point has that potential for me.

What I do know is that unexplained spontaneous remission of stage four cancers is well-documented in the medical literature. Science has also documented therapeutic cures for people who once were considered to have incurable cancers. The scientific literature calls those people living outliers. The odds of being an outlier who responded to therapies for advanced prostate cancer with a cure are probably about the same odds of experiencing a spontaneous remission of their cancer.      

After the oncologist and his team left the room, a geneticist entered and went over in detail what it means to have genetic testing and the ethics of protecting the results of those tests, among a few other details. From what I have read, clinical geneticists are in short supply, and this is why many oncologists don’t do a lot of genetic testing. This is because to perform genetic testing in the most medically ethical way, you are supposed to be counseled by a professional regarding the medical necessity and potential implications of test results. Most, if not all, comprehensive cancer centers have clinical geneticists who do this counseling.

I had already done the “Color” hereditary cancer test. It was a genetic test suggested by the urologic surgeon who performed my prostatectomy. It uses your saliva to test for various germline cancers - hereditary cancers that run in your family’s bloodline. That test was done in his office, and I received no genetic counseling prior to agreeing to the test. Did I care at the time? No. I was just interested to see if there were any genes, such as BRCA2, that ran in my family. My “Color” test showed no germline mutations that would put me at risk for cancer.

Genetic mutations, even the ones that put you at risk for cancer, are rarely going to automatically cause you to have cancer. These mutations are considered one of many risk factors, along with others like smoking, that put you at risk for certain cancers. As a genetic risk factor, most require an epigenetic influencer, such as prolonged stress, hormonal abnormalities, or smoking to trigger these mutations to cause disease.  

Genetic aberrancies that run in a family’s bloodline are called germline mutations. For men with advanced prostate cancer, it can be helpful to test for germline mutations to know if you have inheritable cancer mutations that can be passed down to family members such as your sons and daughters. If you are found to have an inheritable cancer germline mutation such as BRCA1 or BRCA2, your family can make better-informed decisions about testing other family members for these mutations. In addition, knowing inheritable cancer germline mutations run in your family, this information can be used to start certain cancer screenings at an earlier age.

The downside of knowing your family has inheritable cancer germline mutations is that it can cause significant emotional distress, mainly in the form of worrying if other family members will eventually be diagnosed with cancer. This is a perfect example of why it’s so important to be counseled before submitting yourself or family members to genetic testing.   

We then went downstairs to the blood draw area, which was one of the biggest phlebotomy stations I’ve seen in my medical career. There were video screens directing you to your station. Once that was done, we headed to the airport.

While we were sitting on the airplane just after boarding, I received a call from the oncologist’s nurse who gave me all of my lab results. He also made sure I understood how to access the patient portal so that I could access my labs and be able to message him and the doctor.

Overall, my experience at MD Anderson Houston was fantastic. It represents the pinnacle of cancer care in the U.S. It was well worth the trip and the information I gathered helped me to make a better-informed decision about my care. It also made me aware that MD Anderson Jacksonville is like any other highly qualified cancer treatment center that offers multidisciplinary cancer care, but is in no way a cancer center of excellence like MD Anderson Houston.

In the next newsletter, I describe my trip to Los Angeles for PSMA PET scanning at UCLA. While I’m there, another September 25 synchronicity occurs! What are the odds?!?

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