Radicals, Robots and Reimbursement


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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.

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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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Prostatectomy compared to Active/Watchful Surveillance


If you would like to subscribe to this blog, click this link and subscribe on the left of the home page. A new article appeared this week with further fuel for those on the side of intervention (and by implication, pro-screening). Let’s remember before we get started, that the two largest trials of screening vs not screening did not show a very big impact, if any, on finding and treating prostate cancer. Moreover, that treatment is toxic to many men who may not have needed it.

The study is about men who HAVE prostate cancer and are randomized to surveillance versus surgery. This is different from the conundrum of screening. These guys were “caught” by whatever means via a biopsy that found cancer. In the NEJM article from Scandinavia, 695 men diagnosed between 1989-99 were randomized to watchful waiting vs. prostatectomy. Their mean age was 65 and 88% of the men had palpable tumors, different from the more common T1c (PSA only) detected in the current era. Here’s a sobering fact: by 2012, 64% of them were dead. Argh….the end is near!

What we care about is their quality of life and how much of that death was attributable to prostate cancer. We are all going to die of something….just don’t torture us please. As regards death, 63/347 (18%) men in the prostatectomy group died from prostate cancer while it was 99/348 (28%) of the surveillance group. However, the overall death rate was 56% vs 69%, so more men in each group died of something else. There are many kinds of additional analyses in the study, including the death rate from low, intermediate, and high risk cancers, effects of age, time on hormonal therapy, and so forth. The benefit of early surgery seems to be greatest in men under 65 with intermediate risk (Gleason 7) cancers.  As regards quality of life, more men had metastases in the surveillance group and as the authors state, “The cumulative incidence of the use of androgen-deprivation therapy at 18 years was 42.5% in the radical-prostatectomy group and 67.4% in the watchful-waiting group (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3)” My conclusion is that men who are younger (you pick the age…) and have higher grade tumors (any finding of Gleason 4) are probably better off electing treatment than watching. It is certainly possible that surgery or radiation therapy are equally good choices, but that is not addressed here.

My conclusion is that men should still think carefully about stopping screening as they near 70 unless their parents lived into their late 80′s or 90′s and they enjoy superb health. If they participate in screening and are found to have a Gleason 7 or higher cancer, they should be treated. Those thoughts are not new. The studies also support treatment for lower risk patients, but the preservation of quality of life (potency, continence) and lower impact on the development of metastases or dying, make the decision much tougher.

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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….

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Should I take vitamins? What can I do???


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These two questions are among the most commonly asked in my clinic, particularly from patients who are recently diagnosed with prostate cancer. Numerous studies have been done on adding various supplements to the diet, and anyone who reads this blog has already seen my thoughts on pomegranate, milk thistle, green tea, soy, etc. You can find dozens if not hundreds of references and small studies purporting to show a beneficial effect on cancer.

Further, there are studies that show the likelihood of cancer patients using supplements is higher among those with the most education (and probably with more disposable income). I have contributed my own body to this question by participating in the Physician’s Health Study II. For more than a decade I faithfully took first 3, then 2, then one pill daily that was either placebo or a vitamin/multivitamin. The results of this study so far are a big, fat ZERO. Moreover, in looking at this study along with many others, it is very hard to see any benefit from most supplements. An exception might be Vitamin D since those of us who are cancer phobic do such a good job of wearing sunscreen. And patients on androgen suppression may benefit from calcium supplements, although this, too, is controversial.

In the most recent Annals of Internal Medicine, there is further evidence of futility in the 28 BILLION dollar/year vitamin industry. “This review included 26 studies (24 randomized, controlled trials and 2 cohort studies) that examined the benefits and harms of using vitamin and mineral supplements for primary prevention of CVD, cancer, or all-cause mortality in healthy individuals without known nutritional deficiencies. We found no consistent evidence that the included supplements affected CVD, cancer, or all-cause mortality in healthy individuals without known nutritional deficiencies.” The accompanying editorial is entitled “Enough is enough: Stop wasting money on vitamin and mineral Supplements”

So, you can read it and weep, or save your money and buy more veggies and exotic fruits and nuts and enjoy your diet. It’s all up to you (and maybe how many years you went to school after you “grew up” and could critically analyze data). Remember, the more schooling, the higher the tendency to buy/take vitamins. Welcome to dreamland! What you CAN do is exercise and avoid fat.

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More progress – Merry Christmas!


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Men who have metastatic prostate cancer at presentation are now quite rare. In the days before psa screening (which clearly works, but picks up way too many patients with low grade disease whom we don’t need to find…see multiple blogs elsewhere) we used to see 70 year old men come in with new bone pain, and then it turned out to be prostate cancer. In any case, since the discovery of the taxanes (docetaxel and cabazitaxel), the first drugs to prolong survival after castrate resistant disease sets in, we have all wondered if they were used earlier whether there would be an advantage. The earliest they could be used would be immediately after surgery – but the trial that attempted to study this was abandoned after 2 years because not enough men/doctors would sign their patients up. (see blogs on this elsewhere as well)

So… what about using taxanes at the time hormone therapy is first started? (This could be after surgery or radiation…many years…or when a rare patient first presented with metastatic disease. They HAD to have metastases, however, not just a rising psa. The study (which we called CHAARTED – and my colleagues at CU and I offered this trial to many patients and we treated quite a few who were willing) randomized to hormone treatment alone vs hormone treatment (ADT) combined with 6 cycles over 18 weeks of docetaxel. The trial has been reported now in preliminary form and shows significant improvement in survival in the men who received the docetaxel. This is really a trial between “early vs late” docetaxel, since I am relatively certain the men who got ADT alone would have eventually received docetaxel as well when they became castrate resistant. This is a BIG deal. It means that we have a shot at eliminating some of the cells that don’t fully die off from ADT alone right at the start. It also paves the way to go back and look at doing similar treatment right at the time of surgery or radiation, like we tried to do a decade ago. And if we add the newer hormonal agents (abiraterone, enzalutamide, Tak700, etc) up front, the results could be even better (please lobby the companies who make these agents to provide them for free to men willing to be treated in such trials)

Hats off to the men who agreed to this practice changing trial and to their physicians. And congratulations to my good friend Chris Sweeney who headed up the trial. (He and I have had some great times together over the years) Gentlemen, this is what our sisters did to advance breast cancer treatment 30 years ago! Don’t ever tell me it isn’t good to sign up for randomized trials, or that just doing what we always have done is adequate. Support research! Only 4% of U.S. cancer patients participate in clinical trials. Let’s work together to beat this disease. Happy holidays!

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Lengthen your telomeres this week


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For journal club last week, I selected an article that looks at length of telomeres as a prognostic variable for prostate cancer. Telomeres are DNA protein complexes that are added to the tips of chromosomes by an enzyme, telomerase, that carries its own little RNA unit and was involved in one of the authors (Elizabeth Blackburn) of the story below winning a Nobel prize. As you get older, the length of your telomeres shortens, eventually giving rise to loss of important chromosomal information that can lead to cancer. In the journal club article, it was found that men who had shorter and more variable telomere length in their prostate cancer or the surrounding tissue, had a higher chance of developing metastases or dying from their disease. Of course this is bad news, and you might think there is nothing you can do about it. Not so fast….

Blackburn and her colleagues at UCSF have been studying men with prostate cancer to see if exercise and diet can influence telomere length. In a 2008 study, they found that peripheral blood cells had increased telomerase after 3 months of improved diet and exercise intervention. In their most recent study, they find that the continuation of the diet/exercise program results in actual increases in the telomere length in the peripheral blood cells. Since these are men with low risk prostate cancer who are being followed on a study with active surveillance, we will also be learning how such improved life style affects other genetic changes in serial biopsies of the cancers.

For now, the bet is that (as usual) you will benefit from increasing your exercise program, dropping red meat from your diet, and probably watching less football and doing more hiking this week with your family as you celebrate Thanksgiving. I’m just saying….

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