Prostate Theranostics

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Sometimes a great new word evokes curiosity, so I have used it to title this post and see if a few of you thought it would be worth looking at rather than sending to your “junk” email. You can’t find it in the dictionary, interestingly enough, but it’s related in derivation to Theranos, the bizarre company started by Elizabeth Holmes and if you haven’t read “Bad Blood” or seen the video you can find that story here:

For us prostate cancer followers, however, theranostics represent a “new” field in which the same/similar drugs can potentially be used for both diagnosis and therapy. There is a nice review of an ASCO educational presentation on the topic here. The main idea is that a radioisotope can be specifically directed to a target for either diagnosis or therapy. One of the oldest examples of this is radioiodine which is taken up by the thyroid gland. If you have thyroid cancer, the metastases will also take up the radioactive iodine and with nuclear medicine detectors you can see them, or if you inject even more, it will be “hot” enough to kill them.

223Ra is an isotope that seeks bone, just like calcium, and where there is more bone turnover/remodeling, more of it accumulates. As a drug, it was given the name Xofigo, and was approved for treating prostate cancer in men with bone dominant disease in 2013. It emits alpha particles, which are known as “high Linear Energy Transfer” radiation because they go only a very short distance before interacting with cancer cells and killing them. This is important since you would not want the radiation to kill the normal bone marrow cells that live in the same neighborhood. In the study leading to approval of 223Ra, men with symptomatic bone metastases and no visceral (e.g. liver or lung) metastases who received the isotope as a monthly injection for 6 months lived 14.9 months as compared to 11.3 months for placebo (P<0.001) and had fewer skeletal events and less bone pain. I always loved alpha emitters because I had the fun of making a cloud chamber for a science fair when I was in 6th grade. You might want to help a grandchild do that!

177Lutetium (177Lu) is an isotope that allows both diagnosis and therapy because it emits gamma radiation for detection, and high energy beta radiation that can kill cancer cells. When bound to PSMA (see these posts)

177Lu becomes a theranostic that shows considerable promise for treating prostate cancer. There are a number of completed trials of 177Lu-PSMA that have been summarized in this table:

For more details on 177Lu-PSMA treatment, this is an excellent recent review from the European Society of Radiology:

https://epos.myesr.org/poster/esr/ecr2020/C-00307

There are a number of ongoing trials of 177Lu-PSMA that you can find here.

Keep wearing your masks to protect your fellow prostate cancer groupies, be patriotic, and if you want to pay homage to one of the great scientists whose research led to these advances, look no farther than Radioactive, the recent Amazon Prime movie about Marie Curie. As one of the commentators on the trailer posted, “In a world full of Kardashian’s… be Madam Curie.”

9 Comments

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9 responses to “Prostate Theranostics

  1. Juan Rodriguez Ramos

    Hello Dr. Glode,

    Do enjoy your posts.

    I wonder why all these new and exciting therapies are first applied on end stage disease. If the hope is cure why then not use it in early stages of recurrence when the tumor burden is much smaller. I understand that the standard of care is hormonal suppression, however, having been subjected to such treatment I can tell you there is very little quality of life during treatment and at the end of the day is not curative.

    Juan L. Rodriguez Ramos MD

    • Great comment Juan. As you know, the best time to use “effective” therapies is no doubt much earlier in disease. The spectrum goes all the way to “therapy” that would prevent disease in the first place, to the use of adjuvant therapy (e.g. chemo or hormonal treatments immediately before or after radiation or surgery). The issue becomes how to define “effective”. Adjuvant hormone therapy (with its side effects that are unpleasant for sure) improves the cure rate for radiation treatment of locally advanced or high risk prostate cancer. But of course, “we” are then treating a larger number of patients who may have been cured without its use, so the toxicity is experienced by everyone to benefit a fraction. I think the answer really comes down to the toxicity-risk/benefit analysis. Ideally we would have a vaccine with no side effects that could be given to patients with a strong positive family history or genomic analysis that showed they were at high risk (e.g. BRCA2 mutation). When really effective therapies come along (for example platinum based therapies for testis cancer), they are used in earlier disease right away, and then the research focuses more on how to DECREASE the amount of treatment to achieve the same results. Clearly we have a ways to go in pca. It might (or might not) make sense to use a treatment that prolongs survival by a few months in earlier patients, but that’s why we need the clinical trials. Unfortunately, unlike breast cancer, few men with pca are entered into such trials, so it goes slowly. The advances seem to come from places like the UK where “socialized medicine” can more easily do the trials – a political anathema in the U.S.

  2. Tom Remenick

    I thought that was a great question by Dr. Juan Ramos. I have wondered the same thing.
    Just a follow up to your answer Dr Glode – The toxicity issue is easy to appreciate. However wouldn’t a person who is at an earlier stage of the disease presumably be younger and thus more able to tolerate toxic effects. Wouldn’t they be good candidates for earlier treatment with medications that are more typically used for late stage disease? Does the treating physician have much discretion in those situations?

    • Great questions, although there are some interesting issues to consider. Prostate cancer seldom affects “young” people as we know (and of course “young” can be something chronologic as well as biologic. There are 80 year olds in my practice still skiing black diamond slopes, and 60 year olds who spent too much time smoking. The NIH and other agencies encourage registry of all ages (and genders – albeit not in pca obviously) because there is quite a bit of evidence that we shouldn’t “back off” treating older patients. But – you are correct, earlier stage disease generally means better tolerance, and many protocols that test newer (and potentially toxic) drugs, exclude patients with poor performance status to make sure these individuals will really be able to tolerate treatments long enough to see if they work. Treating physicians in clinical trials must adhere to the eligibility criteria which can vary depending on the drug(s) being studied. Outside of a clinical trial, often the discretion to try something new or promising is limited by whether a drug has been approved for a specific stage of disease and is available, or even more frustrating, whether insurance/medicare will pay for it. There is also the issue of endpoints. For most cancers, the most reliable endpoint is survival. This creates a particular challenge in pca where the age of patients means there are many competing causes of death for what is a relatively slow disease. A drug company can seldom afford to wait 20 years for a result, so late stage patients may be the easiest place to get a go/no-go signal. In the SWOG 9921 trial that I had the honor to lead, we looked at whether addition of mitoxantrone to 2 years of hormone suppression would be of benefit. It started in 1999, but we couldn’t get a statistical answer until ~2015. Yesterday, I saw a patient who had his initial prostatectomy in 1994!
      Thanks for the question and hope this helps clarify some of the challenges.

  3. Juan Rodriguez Ramos

    Thank you Dr. Glode and Mr. Remenick for your replies.
    I have no complains at 62 years of age, GS 9 and 9 years post RP, RT/ADT two years ago with undetectable PSA 6 months ago. For now more worried about a bit of RNA given my profession and the fact that my wife is an elementary school counselor in TX. Ha! Talking about living day to day. No worries. However, hoping to learn skiing and go down double black diamonds twenty years from now.

  4. Great post! I like the joke of theranostics and theranos!

  5. Patrick F Gill

    You had me at Prostate. Always read your posts. Would never think of putting them in Junk. I wanna make it into the Black Diamond 80 club, so with 7 years to go, I’ve got to keep reading. Best!

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