“It was a great shame,” a correspondent writes, “that the lead investigator for the first Provenge pivotal trial, Dr. Eric Small, had his flight cancelled by his airline so he was not able to join the panel in time. Dr. David Penson, however, has been an investigator on all three clinical trials for Provenge. During the public commentary section, he clearly articulated how his patients benefited. Dr. Penson came to the CTGT public commentary meeting of his own accord and did not discuss his testimony with the sponsor.”

And so it begins: “of his own accord and did not discuss his testimony with the sponsor.” Why is a disclaimer needed? Why is it even there? Certainly isn’t true in any deep way. Unlike Dr. Small, Dr. David Penson carries a bundle of declared financial interests. He’s a patient’s friend in need, he’s a clinical trials investigator in a field (immunology and oncology) outside of his sphere of training and expertise (urology) and he’s a paid consultant for Dendreon, Sanofi-Aventis and AstraZeneca and a hired speaker for Pfizer and Boehringer Ingelheim. What matters more is whether he thinks clearly enough to know the difference between testimony and evidence.

Dr. Penson is known at USC/Norris cancer center as a urologist who “combines expert care with deep compassion to treat men undergoing radical prostatectomy.” He’s a an expert also in prostate cancer screening and mortality. He co-authored a case-controlled study of a group of men in Veterans Affairs (VA) medical centers who were diagnosed with prostate cancer between 1991-95 and who died between 1991-98. This study drew headlines for its conclusion: “These results do not suggest that screening with PSA or DRE is effective in reducing mortality.”

Dr. Penson doesn’t stand behind that study, though. In an “Expert Interview” with Medscape he said: “The findings may have been different had we looked at prostate cancer-specific mortality, used a more generalizable population, or followed the patients for a longer period of time. I certainly wouldn’t make policy decisions regarding screening on the basis of the current study.” The study used some junk data.

Asked “Did the study show anything new about the digital rectal exam?” Posner said “Not really. You have to remember that the DRE info was taken from VA medical records, and was often obtained by residents. I don’t have a lot of faith in the DRE data in this study.” Can doctors learn anything from it at all? “No. Physicians should be explaining to patients that we really don’t know if screening is a good thing or not, and that it is their choice if they want to get the test. Most men do choose to be screened, and that’s very reasonable. The one thing providers must do, particularly if the patient states that he doesn’t want to be screened, is document that the test was offered. Beyond that, we’ll have to wait for the results from the randomized clinical trials.”

So, why did Dr. Penson sign off on that study, one that muddied the stream of evidence? Dr. Penson was a staff surgeon at Veterans Affairs and won a Veterans Affairs (VA) Career Development Award (2001). VA struggles with costs of treating patients, but they found money for a research project, this one, to confirm that screening men for prostate cancer is unnecessary. Asked by Medscape “Did this study simply confirm what you suspected or was there anything that surprised you about the results?” Dr. Penson said “No surprises here.” And he frankly admits some of its weaknesses.

“The study doesn’t have adequate follow-up, nor does it examine prostate cancer-specific mortality. The men most likely to die in the 5- to 7-year period following a diagnosis of prostate cancer are the ones with the most advanced disease at presentation or the ones with the most associated comorbid disease. Therefore, it is unlikely that you would see any overall mortality benefit of prostate cancer screening in this short window.”

The truth is the method was ludicrous. They would take the records of a patient, Penson explained, say Mr. Smith, a 65-year-old man, diagnosed with prostate cancer February 1, 1991 and died on April 1, 1995. “We then looked at the center’s ambulatory care clinic roles for February 1, 1991 and found all men age 65 who were seen in the clinic that day who were alive on April 1, 1995, when Mr. Smith died. We then randomly selected one of these men to serve as the matched control for Mr. Smith.” If Mr. Smith, who died of prostate cancer with 7 years of diagnosis, had been screened for prostate cancer and his “control” twin, never diagnosed with prostate cancer and still alive, had not been screened, that was taken to show that PSA screening doesn’t work.

If taken seriously, this research would help the budget. Money for screening Vets for prostate cancer and treating those found to have prostate cancer at an early stage could be spent elsewhere.

Junk medical studies, even if not skewed as this one was by economic and political biases, can do damage to the people they are about, in this case older men who depend on the VA as their mainstay medical center. PSA rising ran a brief report on that VA study last year (Screening for Prostate Cancer May Not Reduce Men’s Risk of Dying from the Disease) and also ran a critique by Ralph Valle, who heads up Arizona US Too. His article began: “I see this study as a huge piece of misinformation. They set out to prove a point using very weak data. . . . ” (Critique of the Recent VA Study of Prostate Cancer Screening, Jan 11 2006).

So, the co-author of that piece of misinformation (as Ralph kindly terms it), which made sense as a career stepping-stone but may have left some men to wander untreated onto the road to advanced prostate cancer, now turns up addressing the FDA Advisory meeting as compassionate advocate for men with advanced prostate cancer. After being hired as a principle investigator in Dendreon’s clinical trials, Dr. Penson talked to Dendreon’s investors and told them what they wanted to hear — patients would be crying out for the vaccine. Now he’s a media spokesman.

Before testifying at the public hearing about how much his patients benefited from Provenge, he did an interview with Joanne Silberner at National Public Radio’s Morning Edition. “Penson is bullish on Provenge, but only for the type of men it was tested on,” Silberner said. “‘These are men who have cancer all over their body which no longer responds to the traditional hormone therapy,’” Dr. Penson told Silberner. He said the same thing in an interview with CBS. “This is a very desperate group of patients who have no other options. The cancer has spread all over their body, so that four-month survival advantage really means a lot to these men.”

How did Dr. Penson, a urologist, make the leap to treating men who have cancer “all over their body”? Urologists are not the best doctors to treat advanced prostate cancer patients nor to run clinical trials for them. Men with advanced, androgen-independent refractory prostate cancer are generally advised to consult medical oncologists. Veterans tell other patients this all the time.

Maybe what’s important is that Dr. Penson can switch tracks in a flash if, say, Provenge needs to fit into a different niche than the one proclaimed at the hearing and to the media. A hint was transmitted in May 2006 when Dendreon arranged for Dr. Penson and another Dendreon trials’ investigator, Dr. Evan Roy Berger, to address investors. They teamed up for a “prostate cancer expert” call hosted by JMP Securities and moderated by Dr. Charles Duncan, Senior Biotech Analyst. Surprise, they didn’t say much about men with advanced prostate cancer except, indirectly, to assure investors that patients could be relied on to cry out for this drug.

Who are the patients doctors like these may actually recruit onto Provenge if it is approved? Men with early recurrence, caught as soon as primary treatment appears to have failed. What a market — the market Tap and AstraZeneca mined in the 90s:

Evan Roy Berger: Well, right now, we don´t have anything but hormones in this group of patients who fail.

Charles Duncan: And if they work, how long do they – how much do they delay things? In your view. Just, you know, …

Evan Roy Berger: Well, it’s a difficult question to answer because when a patient first fails a radical prostatectomy or primary therapy and their PSA goes up, it depends on a lot of variables. Because these patients can fail within a year or they can fail four or five years later. And that tells us something about the inherent biology of the disease. We know that some patients’ doubling times are very rapid and others are very slow…… But I think that hormones and hormonal therapy is not particularly a wonderful treatment, as far as patients are concerned. Their quality of life deteriorates. They get weak. They get bellies. They get forgetful. They become anemic and they become osteoporotic. And the quality of life the longer you’re on it is not so good. If we had something that really allows us to withhold hormones for even six months to a year – and we´re seeing a four month difference in metastatic hormone refractory disease – if you can take three infusions of a drug and stop it for six months to a year from progressing, I think we´ve made progress. I expect it to be better than that. But that’s my feeling. I´ll ask Dave what he thinks.

David Penson: Yes. I – you know, it’s as you said. It´s a tough question to answer. What´s the right number. But I completely agree with everything you said. You know, there´s no real good evidence that treating someone with hormones in the setting of a biochemical failure is ultimately going to affect outcome. So to ask,”Well, what’s going to make you use it?” I can’t tell you that. Here’s what I can tell you. Is that in the 90s, if you look at the use of hormone therapy in this country, it’s gone through the ceiling. It’s just gone up and up and up. And a lot of that use is in the biochemical failure setting. Because patients, when they get a PSA – detectable PSA – after surgery or their PSA starts going up after radiation, as any provider will tell you, they go a little crazy. And they want to be treated. That craziness is offset by six months or a year of hormones when they have all those side effects and you’re – you know, as Roy said, you just end up – these patients feel crappy and they want to get off the drug at that point and they start talking about intermittent therapy.

I personally think that patients given a choice between a drug that they can take three times over the course of six weeks and then not have to worry about it again and maintain their libido, maintain their erections, maintain all the nice part of being in the golden age of retirement, as opposed to a drug that gives them hot flashes, that makes them feel run down, they’re going to always opt for this – for the immunotherapeutic agent. I mean that’s just the way I look at it.

What’s it going to take to make me use it? I’m not sure it makes a difference what I think. It’s going to be patients coming in driving this because that’s what happens with hormones right now.

Evan Roy Berger: Most people think that PSA stands for prostatic specific antigen when, in fact, it means prostatic specific anxiety.

Dr. Duncan brought up a final topic:

Charles Duncan: Drs. Berger and Penson …. I’m going to ask you a simple question. What do you think about the awareness, out there, in – within the prostate cancer patient community? Do the advocacy groups have knowledge of Provenge? Are they keeping track, do you think – do you think they’re willing to get behind this drug, perhaps, even if it goes to a panel, and speak up for it?

Evan Roy Berger: Absolutely. I’m on the board of advisers; the medical board of advisers to two support groups, the largest being US Too. And I know that they have published in their online publication, as well as their newsletter to patients, about the trials and how important it is to accrue patients so that we can get the drug out there because of the excitement. So they’re aware….

David Penson: Yes. I can’t add anything to that. I mean, it’s there and the advocates drive things here and they know about this. So they want it.

Charles Duncan: OK. Good deal.

by Jacqueline Strax, April 20, 2007.