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December 17, 2020

Happy Holidays,

I am so pleased to be wishing you joy in the upcoming season (for a change!) rather than hoping that your holidays were joyful.  After such a long year we all need some extra joy.  And I do hope you are able to be safely together with your family and loved ones this holiday season. 

IN THE NEWS

Well, it has been an unusual year, I must say.  It started out normally, rapidly went south, and we are now—hopefully–in recovery.  I remain optimistic and will carry on while being careful. My patient care activities have continued relatively unabated except in May and June when we were in the lockdown.  As what I primarily do is treat patients with cancer, most of my patients have had to weigh the risk of COVID exposure versus cancer progression.  They generally have chosen to deal with the known, and that is their cancer.  They have also chosen to trust that we at Houston Methodist do all in our power to protect them and their health from the virus.  Thank you again for placing your faith and trust in us and your health care in our hands.

As is my norm, I would like to share some highlights in prostate cancer research and treatment that have emerged this past year, along with some of my thoughts. 

GENETIC TESTING

I use genomic tests in men we are considering for active surveillance as a way to manage their prostate cancer.  A number of men are candidates for active surveillance, however, a percentage (15% or so in Caucasians and up to 30% in African-Americans) actually have changes in the genetics of their cancer that tell us that even though pathologic examinations of the cancer indicate it is a slow-grower, their cancer will actually behave like one that is much more aggressive.  Therefore, in these cases, we recommend treatment and not surveillance. 

The genomic test I use is the Oncotype DX that looks at changes within the cancer.  Patterns of genetic/somatic changes are very predictable of cellular behavior.  In men with low-grade, low-aggressive appearing cancer or very small volume intermediate cancer, these patterns helps us know if they are part of the group of men whose cancer will really behave much more aggressively.  The genetic tests for these men I described are very helpful, but again not definitive.  Cancer for men on active surveillance can still progress and change, so these men will still need periodic biopsies, PSA testing, and even repeat genomic tests.  Surveillance is just that—informed observation.

The BRCA-I and BRCA-II genes are very interesting and are advertised as being important in genetic testing.  Knowing whether there are mutations to the BRCA-I and BRCA-II genes does have value, but the value is predominantly in men with advanced/metastatic cancer, as they define which therapies might be best to treat the disease that has spread to their bones. 

It is estimated that up to 10% of men with prostate cancer have genetic changes to BRCA-I and BRCA-II.  The problem is that knowing you have this genetic abnormality is not particularly helpful in telling you whether or not you are going to get the disease.  In a study done in Israel, 7% of the men with these BRCA changes actually got prostate cancer during the study.  Some say the risk could be as high as 1 in 5—definitely higher than the overall risk of the population developing prostate cancer, which is 1 in 9 men.  So, if you get genetically tested and are positive, what do you do?  Well, you get tested/screened earlier, at age 40.  But this is the general recommendation for all men with a family history of prostate cancer and also for African-American men.  Testing your male children in their 20s is also, in my opinion, not to be encouraged.  It can be done, but none of us would recommend earlier screening than age 40 unless Dad was diagnosed in his 40s, in which case screening at age 35 or 37 could be considered.  This is not to say one should not get genetic testing!  My question is, what will you do, what can you do with the information except follow the guidelines that are already in place? 

IMAGING PROSTATE CANCER

Great advances are being made in imaging of prostate cancer.  Current radiologic imaging techniques include CT scans, MRI scans, and bone scans.  These are helpful but limited in their ability to find extremely small volume disease.  PET scans have been extremely helpful in other cancers in the finding of small-volume disease; prostate cancer, however, is very slow growing, so PET scans have had limited usefulness until very recently.  PET—which stands for positron emission tomography—is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes. New PET scans that are effective in prostate cancer have been developed, such as the Axumin PET and the PSMA PET.  The Axumin PET is FDA approved and a welcome addition to our armamentarium for detecting and managing prostate cancer.  

I am excited by the PSMA PET scan.  PSMA stands for prostate-specific membrane antigen.  An antigen is a protein marker.  The membrane antigen is a binding site on the surface of the prostate cells, not inside the cells.  PSA intuitively seemed like a better candidate to target, but PSA is made in the cell and tagging it is much more difficult.  Furthermore, PSMA is over-expressed in prostate cancer than it is in benign prostate tissue making it (hopefully) a great tool for finding disease that heretofore we have been unable to see or detect.  I am happy to announce that with the support of the Houston Methodist Research Institute and its President, Dirk Sostman, M.D., we have a Gallium 68 PSMA PET scanner now.  This one of only fifteen in the U.S. and less than thirty world-wide.  I am now starting to use this too in research projects which I will discuss shortly.

TREATMENTS FOR METASTATIC DISEASE

Much of the news in prostate cancer surrounds metastatic disease.  There is a lot of industry research going on in different biologics and chemotherapeutic agents, and much progress has been made.   These medications will certainly help extend the lives of men, hopefully for years rather than months, but this remains to be seen.  I am sure you will continue to see more on this, but of course these therapeutics are only of value to men who already have metastatic disease, and I am dedicated to trying to prevent cancer from spreading.  My research is on localized disease and trying to cure men, to keep them from moving on to the need for these new agents that are being developed. 

RESEARCH UPDATE

STEM CELLS!  Finally!  After a few years of animal trials and financial challenges I am about to launch my stem cell trial in men undergoing radical prostatectomy.  As you know, removal of the prostate is an important tool in our armamentarium to manage prostate cancer.  The other methods include external beam radiation therapy and high-intensity focused ultrasonography (HIFU).  The major possible complications for all of these treatments include impotence, or erectile dysfunction, and urinary control issues.  These issues are due to the proximity of the nerves involved in erectile and urinary function to the prostate. 

A patient’s own stem cells are a critical component in healing injured tissue throughout our lives.  As we age the quantity of our stem cells decreases dramatically.  We just don’t “bounce” as well in our 60s or 70s as we did in our 20s.  My goal/trial is to give men hundreds of millions of their own stem cells during and after surgery to see if I can eradicate these issues as a complication of surgery.  This is going to be an expensive trial for me to run—over $5000 per patient—which I will be paying for out of research dollars.  I am trying not to charge patients to be part of the trial.  Although depending on overall cost they may have to share a small portion of the total cost involving obtaining their stem cells.  I have just submitted an IND (Investigational New Drug) application with the Food and Drug Administration (FDA) to conduct this exciting and never-before-carried-out trial.  Stay tuned for results which I hope to be able to provide at the end of 2021.

PET SCANS:  As I alluded to in my introductory paragraphs, we are one of only a few centers in the world to have the new Gallium 68 PSMA PET scanner.  I have two trials underway to evaluate the role of this technology in men with newly diagnosed high-risk prostate cancer and men with biochemical recurrence.  Biochemical recurrence means that the PSA, which should be undetectable at less than 0.1, has in fact become detectable.  This means there is prostate cancer somewhere in the body but just not identifiable by the standard radiographic means.  Hopefully PSMA will be able to identify areas of cancer that I can treat focally without resorting to systemic hormone therapy or regional treatment with radiation.  Managing the disease each step of the way can add many years of life while maintaining excellent quality of life.

MITOCHONDRIAL & Metabolomic ABNORMALITIES:  The processes I am describing with the Gallium 68 PSMA PET can be thought of as occurring at a microcellular level.  Along these lines, our microcellular work on mitochondrial (the batteries of the cells) abnormalities and their role in the development of prostate cancer continues.  Because the mitochondrial labs have been pulled into important research about the causes and management of the COVID virus, this research has substantially slowed.  However, our studies have led to the development of yet another new PET scan agent targeted to growth factors associated with the mitochondrial changes we have identified.  We have applied to the Department of Defense for grant funding and remain ever hopeful.  Studies will certainly continue in earnest once we get the virus under control. 

Last year I discussed a very interesting new device created by a young professor at the University of Texas which can detect areas of microscopic cancer.  She and I had been working on details of how to use this too intraoperatively to help me be certain that no cancer remains behind.  Unfortunately, this was in March and as you know, things have changed dramatically since then.  We are still in contact and hopefully in the coming year I can bring this project back to life.

LOCALLY ADVANCED DISEASE:  In tune with extending life, if not obtaining an absolute cure, we have a protocol for downstaging disease that I am very positive about. If a man has regionally advanced prostate cancer growing into the bladder or pelvic lymph glands, we are now first treating with chemotherapy and hormonal therapy.  If we get a response, and we invariably do, I then remove the prostate and lymph glands.  There is a theory that cancer can only spread to other parts of the body from the primary tumor.  That is, the prostate cancer in the lymph glands cannot spread to the bones from there.  A theory!  The Southwest Oncology Group is running a trial that I am part of that is testing this theory to include men with low volume metastatic disease in the bones.  The only issue for my patients is that there is a “placebo” arm where patients will be treated only with chemo or hormonal therapy (usual care) and not be allowed to have surgery or radiation.  This is difficult and most do not want to participate.  Our goal is to see if we are able to extend life and improve the patient’s quality of life through this protocol.  I have treated approximately 15 men so far and they are all doing well but need to be followed for many years to see what our true impact has been.

ROBOTIC EDUCATION:  I am part of a study with surgeons at the University California and M.D. Anderson Cancer Center which is evaluating our skill sets on the Da Vinci Robot and comparing our movements and how we use our hands and feet compared to early or novice users.  The robot is an amazing tool that can track and record every movement of my feet, arms, hands and fingers.  The goal is to see what we, who have done thousands of robotic procedures, do in common with our hands and to reduce those movements to a critical core group of skills to reduce the learning time and skill acquisition for residents and those who want to become superb robotic surgeons.  I am excited to have been asked to be a part of this study.  Being a long-time educator, I too want to know how to teach this skill set better and more quickly.  And perhaps I, too, can learn from this.  You are never too old, after all.

OUTCOMES STUDIES:  My colleagues and I continue to expand and mine my database for outcomes and surgical technique results to publish and share with the urologic community.  Last year I spent a couple of weeks in Korea with Dr. Rah, a leading proponent of a new approach to removing the prostate called the Retzius-Sparing Technique.  His data showed very early return of complete urinary control in his patient population.  I have been using this sparingly in appropriate men to see if this is in fact true in my patient population, as well.  I also continue to explore and study the role of HIFU in the management of prostate cancer.  I have treated approximately 100 men with this device and am very optimistic about its usefulness as a tool to carry out treatment of portions of the gland or focal areas of the prostate where the cancer is located as opposed to removing or treating the whole prostate.  Of course I can treat the whole gland, but also only a portion of it now.  I liken it to the lumpectomy in women with breast cancer—this is something of a male lumpectomy.   Part of my protocol in men so treated is to carry out a prostate biopsy at nine to twelve months after treatment to see the cancer control I have effected in the treatment zone, and also what is happening to the area that was not treated.  It will take many more months before I can report my results.

THE MEN’S HEALTH CENTER 

The Men’s Health Center, with generous support from The Hamill Foundation, is maturing nicely and doing very well.  We now see an average of 200 patients in the center per week.  Many of these are new patients seeking help, usually for low testosterone or erectile dysfunction.  However, many do need primary care physicians, cardiologists, etc., as they have not really been part of the health care system and not taken great care of themselves.  As I had hoped in my original application to The Hamill Foundation, we provide a “new portal of entry” for healthcare for the aging male.  These things do take time to evolve and grow but we certainly have improved our service to patients. 

To assist and make this center function better and in a timely fashion, I would like to introduce Morgan Wilburn, NP.  Morgan will be working closely with me and many of my patients.  She has a remarkable history within the urologic community.  She first worked on the urology inpatient service where she came to my attention as an exceptional nurse for urologic patients. She then went on to pursue her Masters of Science in nursing to become a nurse practitioner.  Morgan has worked with me for approximately twelve months now and has done an excellent job.  She understands the nature of urologic diseases and is very comfortable in examining and treating both men and women.  She has my complete faith.   She may be seeing you from time to time in my stead or my absence, and is available within a day or two should you need to be seen urgently when my schedule does not allow me to see you promptly.  I think you will be very pleased with Morgan’s presence.  I know you will be pleased with her care.

RESIDENT EDUCATION

After the separation occurred with Baylor College of Medicine in 2004, we had to develop a plan to wind down our combined educational efforts with their residency program.  We were an important hospital for Baylor resident education. We were and are saddened by the fact that this had to happen, but we must continue to move forward.  To that end, we created our own residency program which is now in its fifth year and comprised of only Houston Methodist residents.   We have two residents per year for five years of education and we are thrilled to be graduating our first class in June of 2021.  Hoorah!!   All wonderful young men and women (50% of our residents are women).  I think we set the record for approval of a new program by the Accreditation Council for Graduate Medical Education, and the Residency Review Committee in Urology.  It took us six months, which I don’t think has been accomplished before.  Tim Boone, MD, PhD and I are well-known within the urologic community and have been involved in resident education for all of our careers, and I think that had a lot to do with the rapid approval.

EDUCATION AND RESEARCH FUNDING 

In an academic medical institution such as Houston Methodist, an important part of education and research programs are endowed chairs.  A chair is an academic honor recognizing a particular skill set and successful research, an acknowledgment of the reputation and recognition of this.  Besides the clear honor there is an associated endowment that provides a modest amount of money to support research and educational efforts that are not routinely supported by universities or institutions. 

As Vice Chairman of our department, I am working hard to establish a number of endowed chairs in the department to attract highly skilled and respected individuals to help make our department even stronger.  Thanks to the generosity of my wonderful patient Roy Shaw, and his wife, the Judith Helmle Shaw and Roy Gordon Shaw, Jr. Centennial Chair in Urology was established this year.  We hope to use this chair to help attract a top-notch leader as the new chairman of Urology.

The Layton Fund generously established a chair in prostate cancer research that I am privileged to hold. I want to establish a number of other endowed chairs, in particular chairs in neuro-urology/pelvic urologic reconstruction, oncology, andrology, and endourology/stone disease.  Why? you might ask.  Well, to recognize the best and the brightest and to recruit those men and women to further enhance the department and help make it one of the strongest in the country. Chairs are exceedingly important in the world of academic medicine.  The young men and women we want to recruit are the professionals that will change how we practice medicine and treat disease for the BETTER.  We need them.  They need support.  Philanthropic endowments to support academic chairs are not inexpensive, so I have my work cut out for me.  Happily, I have the support of the Houston Methodist Foundation and wonderful people like JoAnn Grisanti.  And, as always, a journey of a thousand miles begins with the first step.  If you would like to know more about this or how to support my research program, please feel free to contact me or JoAnn; she can be reached at 832.567.6542.

RECENT PUBLICATIONS & Academic Activity

Poster Presentations

• 10/2020: High Intensity Focused Ultrasound Treatment of Prostate Cancer: Early Assessment of a New Platform for Focal Ablation of Targeted Lesions (South Central & Mid-Atlantic Section, AUA)
• 10/2019: Expanded Experience with HIFU and Prostate Cancer (Societe Internationale d’Urologie)
• 09/2018: Early Experience with High-Intesity Focused Ultrsound (HIFU) Ablation of the Prostate (South Central Section, AUA)

Publications 

• Neuropeptide Y nerve paracrine regulation of prostate cancer oncogenesis and therapy resistance (The Prostate)
• Influence of the neural microenvironment on prostate cancer (PMID 29131367)
• Moving Beyond Gleason Scoring (Arch Pathol Lab Med.)
• Clinical benefit of treatment for metastatic renal cell cancer at high volume facilities (Ann. Transl.Med)
• Higher neural contribution underlying persistent lower urinary tract symptoms in men with Benign Prostatic Hyperplasia undergoing bladder outlet procedures. (Contemp.Clin.Trial Commun.)
• Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy: A Meta-analysis of Oncologic, Perioperative, and Complication-related outcomes. ( Eur Urol Oncol)
• Histologic features of stromogenic carcinoma of the prostate (carcinomas with reactive stroma grade 3) (Hum.Pathol.)

Thank you, again, for entrusting me and my team with your care.  Here’s to a happy and healthy new year!

Sincerely,

Brian J. Miles, M.D.

Centennial Chair in Urologic Oncology

Professor of Urology, Weill Cornell Medical College

Vice Chair, Department of Urology

Medical Director of Robotic Surgery

Houston Methodist Hospital