Tag Archives: medical economics

3 Articles and a forth


To read this post on my blog site, see other blogs, and sign up for future posts, click here.

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…)

 

4 Comments

Filed under General Prostate Cancer Issues, Prostate cancer therapy, Uncategorized

Olaparib for resistant prostate cancer


To view this blog at my blog’s website where you can sign up to be notified and read other posts relevant to prostate cancer, click here.

In what is the first (and hopefully one of many) example of using modern genomic methods to match treatments to the molecular defects in prostate cancer, the FDA has just granted “breakthrough designation” to olaparib, a drug made by AstraZeneca. This followed a publication in the NEJM with nearly as many authors as patients, illustrating the power of team science and international collaboration.

Cancer cells develop numerous mutations that provide them with the ability to divide, metastasize, escape immune surveillance and so forth. One of the drivers of this mutation cascade is genetic instability, in part due to the accumulation of mutations that keep the cells from correcting DNA alterations. These mutations in DNA-repair enzymes can leave the cancer susceptible to additional inhibitors of DNA repair, one of which is PARP, an enzyme found in the nucleus that detects DNA strand breaks and initiates repair. When olaparib interferes with this enzyme, cells can become so genetically unstable they die.

In the TOPARP-A trial, 50 patients who had castrate resistant prostate cancer and had progressed on second generation anti-androgen treatment and docetaxel were given olaparib. 16 of 49 evaluable patients responded, however the exciting finding was that because these patients participated in the clinical trial and allowed the investigators to biopsy their tumors, it was possible to relate response to the presence of defects in the DNA repair genes. For this subgroup, 14 of 16 responded, indicating that using the repair defects as a biomarker you could predict high response rates, while at the same time, patients without such genetic defects had a much lower response rate (2/33). There is an excellent video that illustrates the results accompanying the publication that you can find by clicking here.

Although this is terrific news for prostate cancer patients, it brings a number of challenges. Testing for genetic mutations is a growing (and somewhat expensive) process. When compared to giving patients a drug that predictably won’t work, however, it can be very cost effective. Second, when you biopsy a tumor, the results can vary depending on where you biopsy as I discussed in this previous blog. “Liquid biopsies” of circulating DNA or tumor cells may provide some help in meeting this challenge.  Third, responses to targeted therapies such as olaparib tend to be rather short-lived, as the cancer cells continue to mutate to find ways around the new agent. The hope would be that combining a targeted treatment like olaparib with an immune approach might bring more prolonged responses. Finally, we must find a way to deal with the extraordinary costs of the new oncology drugs. The actual cost of olaparib is $13,440/month according to this article in the ASCO post. I have previously opined on this issue and invite you to join the discussion by clicking here.

1 Comment

Filed under General Prostate Cancer Issues, Prostate cancer therapy, Targeted treatment

The billionaire cancer researcher


To read this blog on the website where you can find my other blogs and sign up to receive emails, click here.

Several patients/friends told me this week about the 60 Minutes piece highlighting the ongoing efforts of Patrick Soon-Shiong, a surgeon who was involved in the development of abraxane and has become worth $11B as a result. So I did my duty and watched on the Internet tonight and will share my thoughts with you loyal followers. Let it first be said that the optimism in this video is compelling, and for the most part based on science that has been going on for the past decade or so in labs all over the country. The 60 Minutes team working with Dr. Soon-Shiong highlighted in a visually compelling, and mostly understandable way, the progress that is being made using the latest technology and understanding of cancer biology. I will highlight this as follows: 1) massive computer technology and sequencing advances allow “all” of the mutations that characterize a cancer cell to be displayed. 2) Drug development to attack vulnerable biologic pathways within cancer cells is accelerating. 3) The possibility of finding the gene mutations driving these cells by looking at circulating tumor cells portends a [mostly] promising way of sampling what is going on within a patient, yet not having to biopsy the tumors. 4) The recent breakthroughs in enhancing immune responses to tumors by shutting down the innate immune checkpoint controls appears to offer great promise for “wiping out” residual/resistant tumor cells.

With that summary, let me urge anyone who watches/watched the video to pay close attention to my good friend, Derek Raghavan’s commentary. Derek is one of the most insightful and honest translational medical scientists I know. In essence, he points out that although Dr Soon-Shhiong is applying an “all of the above” approach to the attack on cancer, there will still be enormous amounts of work to be done and thereby hints at the problem I have  with the video – overselling hype/hope is a specialty of the media. Presenting the single patient with pancreatic cancer who is doing well is an example of this focus on the “sizzle and not the steak” approach. I take nothing away from what a billion dollars can do to pull the existing technologies together and applaud Dr. Soon-Shiong’s efforts. As a matter of fact, one of the techniques he touches on, using low continuous doses of chemotherapy, is something we may have been the first to try in prostate cancer several years ago and published here.

So what are the cautionary issues? 1) The sheer number of mutations found in most cancers (and perhaps especially prostate cancer where the term “shredding of the genome” has been used, make attacking ALL of the pathways at once nearly impossible.  If even one cell can further mutate in the face of having, say 6 or 7 drugs being given to shut down the mutations, it will survive to become the dominant and lethal metastatic problem. This is layered onto the challenge of using “all 6 drugs” together, which will more than likely compound the toxicities to the host when compared to using one of them at the optimal dose. 2) Tumor heterogeneity. In an incredible tour-de-force, a team of scientists at the Cancer Research UK London Research Institute  did whole genome analysis of the original kidney cancer in four patients as well as in their metastases. The graphic of how the research was done is shown here:

Screen Shot 2014-12-10 at 10.23.28 PM

Each spot in the original tumor as well as each metastasis had a somewhat unique set of mutations. Thus “personalized medicine”, the favorite buzzword of the moment in medicine, has a huge challenge in cancer, since there might be different combinations of drugs required for each metastatic site in some patients. The same might apply even for the evaluation of individual circulating tumor cells of course, which is now possible. A cell coming into the research syringe at one time might reflect a tumor deposit in one area, while the next cell isolated could be coming from somewhere else. 3) The excitement over using the most clever of the immune approaches, including the checkpoint inhibitors and the CART cell approach have significant challenges, either because of unleashing autoimmunity, or the very high costs of manipulating each individual patient’s T-cells in order to come up with the autologous cancer-fighting cell treatment.

So, here’s to the optimism and billionaire strategies, and we all hope it moves forward quickly and successfully. And here’s to 60 Minutes for highlighting the amazing biology and progress that is being made. Hope is one of the keystones of human progress, whether it is landing on Mars or repairing a broken relationship. Love and hope are what make life worth living. May your holiday celebrations be filled with both!

7 Comments

Filed under General Prostate Cancer Issues, Uncategorized

Yay…Movember is here. Let’s kick Pca


Hi friends and relatives (those who will admit it…),

This Movember, I’ve committed my upper lip to help change the face of men’s health by growing a moustache, now I need your support at http://mobro.co/michaelglode.The Movember Foundation is the leading global organization committed to changing the face of men’s health. I’m passionate about this cause because too many men are dying unnecessarily from prostate cancer. In 2014, more than 233,000 men will be diagnosed with prostate cancer. Even better, join our team and donate to yourself and invite your friends/family to the cause! Our team is here: http://us.movember.com/mospace/index/search/?q=university%20colorado

 The Movember Foundation is working tirelessly with an urgent goal in mind: accelerating breakthroughs in prostate cancer research that will benefit patients and their families. Movember is achieving this with the formation of the largest, global alliance of prostate cancer researchers and clinical specialists, who are tackling the toughest prostate cancer challenges. I had the privilege of hearing the updates on the research they have been sponsoring last week at the PCF retreat. More progress in the last 5 years than in the previous 25. Take a look there for updates/posts yourself!

I need your support to fund this important work. Together, we can create a world where no man dies of prostate cancer.

You can donate by:

– Donating online at http://mobro.co/michaelglode (and follow the pathetic growth of my not-so-manly moustache…)

– Writing a check to ‘Movember’, referencing my registration ID: 5798901 and mailing it to:  Movember, P.O. Box 1595, Culver City, CA 90232

You can learn more about the important work and impact Movember is having at: http://us.movember.com/programsThere’s a lot riding on this moustache, thank you for your support!

 Mo Bro Michael Glode

http://mobro.co/michaelglode

Leave a comment

Filed under General Prostate Cancer Issues

Radicals, Robots and Reimbursement


To view this post on the website and subscribe to receive emails, click here.

So how did the robot take over??? As I recall, it started with “hospital A” buying the fancy robot for their urologists to use, after said urologists insisted that this was the way of the future. The Intuitive Surgical Company did an outstanding job of selling the technology. I remember going to our parking lot, going into a fancy 18 wheeler, and playing with the robot, tying a few knots on a fake surgical template, and thinking “really cool”. Of course any boy (and probably a lot of female surgeons as well) loves new toys. Why only this last Christmas, I bought myself and my adult children several of the very cool (and I still recommend them for your toy loving children by the way…) RC indoor helicopters.

But back to “hospital A”. The results of their investment of about $2M plus several hundred thousand in maintenance costs was that patients flocked to their urologists to get their prostates removed by the “new, improved….step right up sir” technology. And of course our hope was that there would be improvements in cure rates, preservation of potency, and less incontinence since there was NO doubt that the surgeons could see their tissues better, control their shakiness, and relax at a console rather than accomplishing the acrobatic feats required for reaching way down behind the pubic bone to get at the evil prostate. And so….the urologists at “hospital B” started losing cases and lobbied their hospitals to take the plunge and also invest. In the end, robotic surgery replaced open prostatectomy in 85% of cases. But, in the three areas patients care about most – cure, potency, continence – there was no improvement. There were very small improvements in blood loss (which for most patients never requires transfusion anyway), time in hospital (reduced from something like 28 hours to 24 hours), and pain (which has always been very minimal anyway, usually handled easily by a few vicodin tablets for 2-3 days). But Intuitive made out like a bandit. Their stock price soared from $12.75 on Dec 22, 2000 to $540 on Apr 3 of 2014. I should have seen this coming!

And now comes this article in today’s JCO: Comparative Effectiveness of Robot-Assisted and Open Radical Prostatectomy in the Postdissemination Era. The authors use the SEER database to evaluate open versus robotic radical prostatectomy (RP) in 5915 patients who had their procedures done between 10/08 and 12/09. 42% of the patients had open “old fashioned” open RP’s (ORP) while 59% had robotic RP (RARP). As stated in their abstract, “patients undergoing RARP had similar odds of overall complications, readmission, and additional cancer therapies compared with patients undergoing ORP. However, RARP was associated with a higher probability of experiencing 30- and 90-day genitourinary and miscellaneous medical complications (all P ≤ .02). Combined with numerous other articles showing no improvement in cure, potency, or incontinence, this paper adds to the rather sad tale of how sometimes our technology leads to higher costs with minimal if any benefit. You can read elsewhere in this blogsite about similar findings with proton beam therapy. “Let the buyer beware” should become a more frequent paradigm for medical advances. Of course if Medicare did this, we would hear the chorus chant the echo chamber commentary on how “government is stopping us from getting the care we deserve”. If you like this system, just continue to vote for no change in how we deploy our Medicare tax dollars.

5 Comments

Filed under General Prostate Cancer Issues

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.

4 Comments

Filed under General Prostate Cancer Issues

The challenge of new drugs


Long long ago, I had just finished my fellowship in medical oncology and moved from Boston to Denver. In the lab, I was working on an obscure enzyme that seemed to differentiate leukemia from normal cells, cystathionase. In the clinic, we had very few clinical trials, so I wrote a cold call letter to 10 different pharma companies. Only TAP Pharmaceuticals wrote back. They had developed a new drug that ultimately became Lupron, and we had the opportunity to participate in all of the trials that led to its approval. The biggest shock I had in that experience was the cost that TAP charged, although by today’s drug standards, I guess it was a bargain.

A few years later, we were asked to participate in the trials that led to approval of goserelin, or Zoladex™. My anticipation was that if approved, the costs of both drugs would drop as the companies competed for market share. It didn’t happen. There are of course many reasons, the greatest being that physicians generally didn’t worry too much about how much a drug cost….insurance or Medicare picked up the cost. Instead, the two companies competed with favors to physicians. Many urology practices made huge profits from the mark-ups in drug, and ultimately TAP paid one of the largest fines in history for unethical practices.

With the new drugs, notably abiraterone and enzalutamide, there have yet to emerge competitors that are approved. The drugs both work on the androgen stimulation axis, but via different mechanisms I have covered elsewhere. Each is incredibly expensive, around $6000/month. But beyond the above “no compete” story, I am concerned that competitors may never even reach the “podium” to provide competition (whether financial or in marketing). The reason is that prostate cancer is inherently slow and that the FDA requires survival as an endpoint. Add to this, that if a patient is on a new drug with some modest improvement in survival, this can be overwhelmed by patients going onto one of the other actives after they progress (rising psa or new lesions on scans) that will make it difficult to see the contribution to survival by “new drug”. The placebo patients will benefit equally from the new approved drugs. This may well be what happened to orteronel, (TAK 700) that was reported to have missed its survival endpoint needed for approval at last weeks ASCO GU meeting. Although I would  like to think that approval would result in lower prices for all of the new drugs, the experience described above makes me skeptical. So how about a new approval process? If a drug is clearly (and I’m not judging whether orteronel is or isn’t the equal of abiraterone here) a comparable, approve it IF the company will provide its “me too” drug to patients at a substantially reduced price. There would still be an advantage for companies to race to be “first to market” and they would enjoy the high profits of being the winner with a new category of drug. On the other hand, competitors could still expect to enter the arena and do well, perhaps competing for first place by price rather than some minor difference in side effects or similar. HOWEVER…this assumes that Medicare, physicians, and insurers would prescribe based on cost savings, something currently forbidden by Medicare but allowed in the VA administration.  And then there would be the fancy TV ads trying to convince patients one drug is better than another based on sitting in bath tubs and looking at sunsets….

7 Comments

Filed under General Prostate Cancer Issues