Tag Archives: radiation therapy

3 Articles and a forth


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OK, I admit to a sleazy, seemingly misspelled word to attract attention. At least I didn’t tweet it at 3AM. So what about the “forth”? I’m using it to remind you to sally forth in your search for information about prostate cancer. I previously wrote a blog giving some practical instructions on how to find the latest research publications on prostate cancer that you can find here. Another possibility, if you want to be overwhelmed is to subscribe to the Prostate Cancer Daily, published by Uro Today. So far as I can tell it is open to all, presents the original abstracts, and links via PubMed to the article itself. I now realize that the prediction of patients knowing more than their doctors about a given condition is glaringly obvious, something I discussed when I first wrote about the Internet and Oncology two decades ago.

So, on to the 3 articles: Typically, the most important articles in medicine are published in high profile journals. The premier one for medical oncology is the Journal of Clinical Oncology, JCO. The editors recently published a “best of genitourinary cancer, 2017” edition in coordination with what we medical oncologists call “GU ASCO” (actually co-sponsored by ASCO, ASTRO, and SUO). I thought it would be of interest to briefly re-cap the 3 prostate articles chosen for that edition.

ARTICLE 1: Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial. This study compared the more potent anti-androgen, enzalutamide (Xtandi™) to the older drug, bicalutamide (Casodex™) in patients who had become resistant to initial hormonal therapy. About 2/3 of the men had positive scans, while in 1/3 the resistance was detected only by a rising PSA without a positive scan. As we might have expected from the way enzalutamide was developed, it was clearly superior, with progression free survival of 19 months for enzalutamide vs. 6 months for bicalutamide. In an ideal world, we would use enzalutamide instead of bicalutamide in almost all cases where an antiandrogen is indicated. However, the increased cost of this drug is dramatic, and there may be other options or confounding issues with interpretation of the study.

ARTICLE 2: Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer. This article reports on one of many studies looking at whether radiation therapy treatment times can be safely shortened by increasing the dose of radiation given with each treatment and giving fewer treatments (fractions). The underlying principles are that tumor cells cannot repair DNA damage from radiation as quickly as normal cells, so giving radiation in small fractions daily allows killing of the tumor while normal cells repair most of the damage. Giving all of the radiation at once would kill every cell (and the patient).  Experimentally, prostate cancer cells may be more susceptible to larger fractions, and this study demonstrated that a radiation therapy course could be safely shortened from 41 sessions to 28 sessions with similar “cure” rates at 5.8 years of followup. This is a general trend in radiation therapy for prostate cancer. Using newer radiation focusing technologies (IMRT, IGRT, Stereotactic radiosurgery, etc.) it is possible to treat prostate cancer with as few as 5 treatments, although the long term efficacy is still unknown, and the addition of androgen deprivation to radiation treatment at any dose also improves efficacy. How to combine these approaches, the optimal duration of ADT, and which patients should stay with the older methods is still uncertain.

ARTICLE 3: Improved Survival With Prostate Radiation in Addition to Androgen Deprivation Therapy for Men With Newly Diagnosed Metastatic Prostate Cancer. Proudly, many of the authors on this article are from the University of Colorado Cancer Center. The authors used the National Cancer Database to determine whether patients with metastatic prostate cancer, traditionally treated with hormone therapy (ADT) only (although more recently with hormone therapy plus chemotherapy) benefit from also radiatiScreen Shot 2015-10-30 at 11.02.16 AMng the prostate itself. The analogy would be burning down the barn after the horse has left (with apologies to my radiation therapy colleagues who never like to compare radiation
treatments to burning). The patients who had their prostates radiated
had a 5 year survival of 49% compared to 33% for those receiving ADT alone. Removing the prostate surgically also worked. The prostate may also be a site where metastatic cells from another location return, as illustrated in this picture and discussed here. The take home message is that the cancerous prostate may continue to “seed” cancer cells to the rest of the body, or be a home for circulating tumor cells and getting rid of it, even though not curative, may be a good idea (toxicities and costs aside).

Consider yourselves updated! (sort of…)

 

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No pain, no gain?


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One of my patients last week had a heartfelt discussion regarding the survival benefit of ADT vs his quality of life. He enjoys body building and showed me some pretty dramatic pictures of himself during his last ADT cycle (on intermittent therapy) versus now, when he had been off treatment for ~6-9 months. Added to his concern was his decline in libido and sexual function during ADT, a common complaint especially among younger patients. The question of quality vs quantity of life was,of course, utmost on his mind.

Starting from the initial diagnosis, every (maybe that should be every !!) prostate cancer patient will experience a decrement in quality of life. Those who elect “watchful waiting” will nevertheless experience anxiety regarding the shadow of CANCER following their footsteps. Sure, you can put it out of your mind, but turn around and there it is, like the neighbor’s unwanted cat stalking you. Then there is the anxiety over what the next PSA will be. And if on active surveillance, what will that next biopsy show?? These issues are both real, disturbing, and often under-appreciated in the discussions surrounding screening…”we should still be screening, but not treat the men who don’t need it…” Really? What about the 80% of men who die at age 90 with prostate cancer at autopsy who never had to deal with the shadow? (The inevitable counter-argument is, “yes, and what about those who had early detection of a high grade cancer whose life was saved?”)

We also tend to ignore the impact of competing mortality in our discussions. “Sure you had a stent placed last year, and you already survived that small colon cancer, so why wouldn’t we be aggressive in treating this new problem?” Dr. Sartor provided an elegant discussion of this in an editorial on the PIVOT trial you can read here. Whatever the flaws in that study, it remains clear that we are not very good at predicting the non-prostate cancer “future” for our patients, and the older you are, the thinner the ice gets regardless of how many marathons you run.

When patients choose one form of primary treatment vs another, they are weighing the different side effect profiles of surgery or radiation as much as which is “most effective”. I often give patients a copy of this article from NEJM and encourage them to spend some time looking at the graphics in Figure 1 to get some idea of what they will face in the way of side effects from treatment. As any honest physician would tell them, treatment will involve side effects, some permanent, in the best of circumstances.

In the setting of more advanced disease, for example a patient who presents with metastases outside the pelvis, the recent CHAARTED and STAMPEDE trials both suggest an advantage to the earlier use of docetaxel chemotherapy in combination with ADT as opposed to ADT alone. These data suggest that “pay me now or pay me later” analysis favors the “pay me now” approach in terms of overall survival. But at what price for quality of life? Fortunately most chemotherapy side effects are reversible, but distinctly unpleasant, potentially making the equation something like “4 months of misery to provide 14 months of longer life….not all of which will be great anyway”.

Even in the very advanced setting, there is some evidence that greater toxicity results in improved survival. A recent analysis of the TROPIC trial of cabazitaxel suggested that the patients who had the most “toxic response” in terms of dropping their neutrophil count benefited the most in terms of overall survival.

While all of this seems incredibly negative (for which I apologize), the history of oncology as a field has been the incremental improvement in survival AND the development of newer treatments that provide such advances with diminishing toxicity. Pediatric leukemia, as discussed extensively in “The Emperor of All Maladies” is a great example of how pioneering patients and physicians worked together to find cures and reduce side effects. We may only be at the beginning of such achievement in prostate cancer, but with the advent of the newer hormonal and imaging agents, increasingly sophisticated surgery and radiation, vaccines and immunotherapy, and even the chemotherapies now available, we have  no doubt reached the end of the beginning. Onward!

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Oh, no! My PSA is going up….do something….


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One of the most frustrating and frightening things that can happen to a prostate cancer patient is for there to be a recurrence of the PSA after he thought he had been cured by surgery, radiation therapy, or both. This is entirely understandable. It is no picnic to go through those treatments in the first place, and when the PSA is clearly going up, it can only mean (with very rare exception) that there are still cancer cells lurking somewhere in the body. The rate of the PSA rise can predict how long it will be until something shows up on a scan, and on average, this is about EIGHT years. The median time to death from prostate cancer after a PSA recurrence is 16 years.

For >95% of patients there is something that CAN be done to stem the rise in PSA. That is to go on hormonal therapy (androgen deprivation, ADT) which will drop the PSA, often all the way to undetectable levels, in over 95% of patients. Voila! Both patient and physician feel much better emotionally. But for the patient, there is a significant price to pay. Namely the hot flashes, loss of energy, weight gain, bone calcium loss, lack of libido and further decrease in sexual function to name a few. The question is whether this is “worth it”.

A study to be presented in the next few weeks at ASCO’s annual meeting, suggests it won’t make much difference if you start ADT early versus waiting until metastases, or perhaps even symptoms occur. Utilizing the CaPSURE database, the investigators evaluated over 2000 men who had PSA relapse. The estimated 5 year overall survival (87% vs 85%) and 10 year overall survival (72% vs 72%) were the same regardless of whether the men received immediate or delayed ADT. The same was true for death from prostate cancer…no significant difference. There are of course other considerations that may come into play like treating those patients who have highly aggressive disease earlier because one knows that there will be metastases within a year, or the patient simply can’t live with himself knowing his PSA is going up.

In my experience, it is the exceptional patient who is willing to go play golf or travel or enjoy his grandchildren and forgo PSA testing on a regular basis. I have trouble even convincing my patients to extend their PSA testing to 6 months from 3 months. The question is, does it make any sense to watch this “number”, any more than it would to have cardiac catheterization every 3 months to follow the slow but inexorable accumulation of calcium in your coronary artery? Or what about the 0.01 mm increase in your abdominal aortic aneurysm? Or the accumulation of two more tangles in the Alzheimer plaque in your brain. Just because we CAN measure PSA so easily certainly doesn’t mean we SHOULD, and I have seen far too many men let this number ruin their otherwise healthy lives.

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No surgery or radiation. Just make my PSA go down!


To read this blog on the website and have access to subscribing and older posts click here. What if you could avoid all of the well-known side effects of surgery or radiation and just take hormone therapy? (aka Androgen Deprivation Therapy or ADT) Given the incredible power of the PSA value to drive thinking of both physicians and patients, this question makes a lot of sense. >95% of patients will have a PSA response to ADT, usually in the form of GnRH agonists (e.g. Lupron, Zoladex, Trelstar, etc) or antagonists (Firmagon, Plenaxis) You might imagine that dropping the PSA would be all that is needed in some men and if they didn’t have too many side effects (weight gain, hot flashes, muscle weakness) they would benefit from the treatment.

A study just reported looked at 3435 men treated in this way between 1995 and 2008 to determine if such treatment would reduce death from prostate cancer and compared them to 11735 men who did not receive such treatment. The age ranged from 35 to >80 and as you might suspect, there was a statistically significant tendency to use treatment in older individuals, in men with higher PSA at diagnosis, and in those with higher Gleason scores. Anyone who received radiation or surgery within the first year after treatment was excluded from the analysis. The bottom line is that there was no effect of using such treatment. To quote the authors, “Our main conclusion is that PADT does not seem to be an effective strategy as an alternative to no therapy among men diagnosed with clinically localized PCa who are not receiving curative-intent therapy. The risks of serious adverse events and the high costs associated with its use mitigate against any clinical or policy rationale for PADT use in these men.”

This study adds to the complexities surrounding prostate cancer diagnosis and treatment. Screening and treating patients with surgery or radiation after age 65 may not produce any positive results in the large screening studies, or at the least, you have to treat a significant number of men who would not need treatment to save one life. While you can make the PSA go down with ADT, it also does not save any lives. Such is the challenge of whom to diagnose, whom to treat, and how to best treat anyone who you think does need treatment. On this blog you will find many entries on these issues, and as I have stated before, when you ask men who are dealing with the disease, they virtually all think their treatment either saved their life or was given too late – illustrating the difference between a population and an individual view. The silver lining is that whether you are diagnosed with pca before you die or not, regardless of treatment choice, you are more likely to die from something else.

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Is medicine a profession or a business?


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I have been thinking about writing a blog like this for some time. So first let me make some disclosures: ONE: I am generally a “liberal” and would favor a single payor health care system. TWO: I grew up in a small town in Nebraska where the local doctors were beloved, cared for the families in our town, and drove Buicks (BMWs, Teslas, Lexi, etc. were unknown – the two bankers drove Cadillacs) THREE: Medicine was much less complex, much cheaper, and much less effective. FOUR: I have had a wonderful career in academics where I received a paycheck from the State of Colorado and was usually required to earn >90% of my salary through grants or clinical earnings – I could talk more about “tenure” if anyone is interested. Academic salaries are generally less than private practice, but the advantages of no/minimal night call and working with residents and students and exploring new treatments in the lab and clinic are great rewards that can’t be measured in dollar terms.

With that out of the way, I remain saddened by what has happened to my profession. For all kinds of reasons, many physicians now consider themselves as much “small businessmen” as they do physicians. As the business of medicine has become more and more complex, they provide jobs for increasing numbers of staff, pay higher malpractice premiums than they used to, and look for ways increase their incomes. But few if any are missing any meals, and many are privileged to be in the top 1% of wage earners. Nothing wrong with that.

BUT… This week’s New England Journal article exposes a very disturbing issue that I happen to know a lot about. Some urologists, who only a decade ago were constantly arguing with their radiation therapy counterparts on how much better surgery is for treating prostate cancer, have been buying radiation therapy equipment and hiring “their own” radiation oncologist to run the equipment, then self-referring. The reason is obvious and it has nothing to do with what is best for patients. It is to increase their already very substantial incomes, which (to be fair) have been decreased somewhat by lesser reimbursement for surgery, less for giving lupron, and no doubt other cuts. The outcome of radiation and surgery treatment in terms of cure is the same. The side effects are somewhat different and deserving of discussion with each man who chooses treatment. The figure shows the magnitude of this trend.

Screen Shot 2013-10-27 at 2.06.09 PM

There are many examples of similar trends when doctors stand to make money by ordering tests, buying their own equipment, setting up their own “surgicenters”, or in my own subspecialty, giving one chemotherapy that has a higher reimbursement than another that is equally efficacious. Other articles have dealt with how hospitals maximize their profits with the “chargemaster”. And still others have dealt with the practice of pharmaceutical companies charging huge amounts for novel drugs – expensive to develop for sure, but also hugely profitable.

So the answer to my question seems to be that medicine is both a profession and a business. My view is that the patient should always come first, not the pursuit of profit. Thus there is a built-in conflict if the goal of business is to make as much money as possible. Herein lies the challenge for our health care system. I don’t have any idea if the ACA will help, but I do know that the current system is in dire need of reform, and that the entering medical students who say they want to be doctors “because they love science and love people” will have a long ways to go in realizing that dream if there aren’t changes.

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October 27, 2013 · 5:29 pm

Profiting from “YOUR” prostate


Medicine is a business. I get that. It is also a wonderful professional calling and being both at the frontiers of science like the genome project as well as holding the hand of a patient who is asking about whether he should try one more desperate treatment is a remarkable privilege. Since I started my medical practice 34 years ago, the changes in both business orientation and in the technologies of medicine are breathtaking. All of that said, I remember when the doctor in my home town of Chadron, Nebraska, made house calls, drove a Buick and lived a few blocks away in a very modest house. Making himself rich was really not part of the equation, although he did well enough to send his kids to fine colleges and eventually build a nicer home.

The skewing of medical practice towards being a “small business” and away from a profession bothers me. Even though I agree with my sister who married a wonderful cardiologist and has a remarkable estate that “once doctors could actually DO something, it became a transaction”, it simply bothers me. My introduction to this real world started when we participated in the development of leuprolide, giving the first patients small but increasing doses, assessing saftety, and eventually designing the trials that led to FDA approval. When the price for a 3 month injection was announced, I was astonished. When a “me too” drug came out called Zoladex, I thought that the competition between pharmaceutical companies would drop prices. It didn’t. Instead, companies competed on behind the scenes pricing schemas that began to corrupt the doctors prescribing the drugs. Eventually (though not soon enough to save billions of dollars to our Medicare system), there was a whistle blower who got enough attention to stop the practice.

Now we find that business and profit have become the (maybe that should be THE) driving force in medical decision making. Urologists who used to make large sums of money off of the drug markup schemes with lupron, changed over to doing more orchiectomies as soon as the profits fell off. The study documenting this found the following: “The use of medical castration increased from 2001 to 2003, whereas, over the same period, surgical castration decreased. Total allowed charges for medical castration peaked in 2003 at $1.23 billion. After the enactment of the MMA, surgical castration rates increased, and medical castration decreased. Total allowed charges for medical castration in 2005 dropped 65% from the 2003 peak.” In other words when the profits for giving Lupron fell, surgeons started doing more surgery and stopped giving leuprolide shots in their offices.

Now the focus has shifted to seeing if more money can be made doing radiation therapy than surgery. Medicare has decreased the compensation for doing prostate surgery.  Some large urology groups have formed and purchased their own radiation therapy equipment. .No problem with that if their practice of recommending surgery versus radiation for patients hasn’t changed. However the data for some of these groups suggests that is not the case. In a recent article from Bloomberg, the profit motive influences more and more urologist’s decision making. “one in five U.S. urologists add to their income by billing for the type of treatment in question, according to the journal Urology Times. Called intensity- modulated radiation therapy, or IMRT, it uses imaging software to focus multi-angled X-rays on tumors, aiming to deliver bigger doses with fewer side effects than prior technologies. This side business pays doctors up to $40,000 per patient from Medicare, or 645 times what a urologist gets for a standard office visit, and as much as 20 times what the federal insurance program pays a surgeon to remove a cancerous prostate gland, according to published studies. Reimbursement from private insurers for IMRT can be even higher, urologists say.”  Dr. Cooperberg, of UCSF is quoted as follows: ““Doctors do what they’re paid to do” Cooperberg said. “If you tell them they can earn $2,000 for surgery or $37,000 for IMRT, what do you think will happen?”

The article goes on to state: “When urologists have a financial stake in IMRT, the portion of patients referred for it roughly triples within about two years, according to preliminary data presented at a radiation oncology conference in Miami Beach last year by Jean Mitchell, a health-care economist at Georgetown University.”
I find all of this very sad. I know dozens of urologists who are absolutely terrific and would never let profit influence their decisions on a treatment recommendation. I also know radiation oncologists who are incensed that urologists are invading their own profit making world, and of course there is no shortage of medical oncologists who “struggle to make ends meet” by giving the most expensive chemotherapy when they should be referring patients to compassionate hospice care. My point is that I don’t think very many medical student applicants start off with making money as their motive for going into medicine. I am disappointed in what my profession seems to do to some of them. I love medicine as a profession, not as a business.

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HDR as an alternative


I don’t think I have previously covered this, but an article in the Journal of Urology is a good reminder of another modality that is not often discussed with patients. High Dose Rate brachytherapy is a method of treating cancer by inserting a highly radioactive seeds into the prostate via catheters and leaving them for a brief time to radiate the tumor. It is different from LDR brachytherapy or “seeds”, which you can read about here. In the LDR procedure, the seeds remain in the body for the rest of your life, while in the HDR methodology, they are inserted, and then removed several times, depending on the way the radiation oncologist wishes to plan the delivery of the radiation dose. As with LDR, HDR can be combined with external beam treatment and/or androgen deprivation. There are several centers with expertise in this technique, including our own, headed up by Dr. David Raben. Whether this is the “best” treatment for any individual, unfortunately, can’t be answered because of the lack of randomized studies. As I have said before,
“there must be 18 ways to destroy your prostate”, and each of them has advantages and disadvantages.

 

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