New nanoparticle-based PSA test: preliminary data

A new article to be published in the Proceedings of the National Academy of Sciences is claiming that nanoparticle-based technology may predict prostate cancer recurrence much earlier than standard or even ultrasensitive PSA testing.

The abstract of the article by Thaxton et al. became available on line on October 24. However, reports about the article had appeared earlier on Bloomberg News, on WebMD, and on HealthDay

According to Bloomberg News, the “new method detected a protein specific to prostate cancer” — prostate- specific antigen (PSA) — “in 86 percent of blood samples compared with 25 percent for conventional tests.” According to HealthDay, the “ultra-sensitive PSA test uses gold particles that are just 30 nanometers in diameter and have antibodies to PSA as well as strands of DNA, the basic genetic molecule, attached to them.”

One of the researchers is also a director of the company (Nanosphere, Inc.) that is developing this technology, and so it would be wise to interpret what is very early data with some caution. However, according to this researcher, the nanotech gold particles allow “detection of PSA at levels 300 times lower than is now possible.” A media release from Nanosphere, Inc. (the company developing this technology) is also available on line.

While the ability to detect a rising PSA extremely early after initial treatment may be highly beneficial in some cases, it has to be said that the benefits may be less evident in others. To illustrate this, we offer the following (relatively common) case example.

Gerry was diagnosed with prostate cancer in 1994, when he was 69 years of age. His PSA was 3.7; he had T1c disease; and there were two small foci of cancer found in one lobe of the prostate in an 8-core biopsy. His Gleason score was 3 + 4 = 7. He went up to New York, got a radical prostatectomy from one of the best prostate cancer specialists in the country, and his pathology report showed only one change — a Gleason score of 4 + 4 = 8. However, his surgeon said, “I am as sure as I can be that I ‘got it all.’ Obviously I can’t promise that a few cells might not have escaped, and we are going to be rigorous about following your PSA, but I think and hope that you are in good shape.”

His surgeon seemed to be right. In 2006 Gerry had had a small heart attack, but recovered well. For 13 years, until June 2007, Gerry’s PSA was < 0.1 ng/ml. He was fully continent and (until his late 70s) pretty much as potent as he had been before the surgery. In his mind he had been cured. Then the PSA started — very slowly — to climb.

By July 2009 the PSA had reached 0.45 ng/ml, and Gerry was starting to wonder whether he needed second-line therapy. By this time Gerry had reached 84 years of age, and on September 15, 2009 Gerry died in his sleep after a second, massive heart attack.

Now if we had had this new nanoparticular PSA test in 1994, then by 1995 we would presumably have been able to tell that Gerry had a rising PSA. He would (probably) have undergone a whole bunch more investigations and treatments for his prostate cancer. He would have been worried about all of this. Further treatment might have affected his contience and his potency. And at the end of the day, nothing good would have come of any of this because Gerry had a classic case of slowly growing prostate cancer that had micrometastasized to his bone marrow, where it couldn’t be found, but it was placing him at minimal risk of death from his disease (especially compared to his heart condition).

While this new form of PSA test (if approved by the FDA, and if it is really as sensitive as projected) will certainly have value, it is also going to need to be used with great caution. It is bad enough already that we over-treat men who may not need treatment at all. It certainly won’t improve the situation if we compound the problem by further over-treating men with very slowly progressive (or even indolent) micro-metastatic disease on the basis of a PSA test that is so sensitive it is detecting clinically insignificant progression.

Caveat emptor!

2 Responses

  1. The example you gave is exactly why I don’t get the ultrasensitive PSA test now. I don’t want to spend the next however many years watching an ultrasensitive test go up and down. Nobody will give you any kind of secondary treatment until your PSA is above 0.1 ng/ml anyway. So until that day comes I’ll take living ignorantly about my PSA.

    My pretreatment PSA was 2.76 and had only risen 0.35 in 5 years and I was organ-confined, Gleason 6, with tertiary grade of 0. I am hoping it will take 10 years before my PSA breaks 0.2 — if it does. I don’t want to watch a slow rise and sweat it out for the next 10 years. Ignorance is bliss …

  2. This was exactly my reaction when I read this in the NY Times yesterday — yet another test which could lead to overdetection and overtreatment! “If you look for more cancer, you will find more cancer”.

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