Post-surgical enrollment in clinical trials by cancer patients

The national rates of participation in clinical trials by cancer patients have never been particularly high. The National Cancer Institute states that, “less than 5 percent of adults diagnosed with cancer each year will get treated through enrollment in a clinical trial.” Naturally this affects our ability to develop new devices, new drugs, and new diagnostic tests and bring them to market as quickly and as cost-efficiently as possible.

However, according to a new study published recently by Al-Refaie et al., the levels of post-surgical enrollment in clinical trials by men and women in California who received surgery as first-line therapy for any form of solid tumor (prostate cancer very definitely included) are doing nothing to help this situation.

Basing their analysis on data from the the 2001–2008 California Cancer Registry, Al-Refaie and his colleagues showed that:

  • 1,566/244,528 patients with a solid tumor (0.64 percent) enrolled in clinical trials after first-line surgical treatment of their cancer.
  • Black patients were less likely than whites to enroll in trials (0.48 vs 0.67 percent, P < 0.05).
  • Older persons (>65 years), people with early stage cancer, and people with lung or gastrointestinal cancers were also less likely to be enrolled in cancer trials.
  • Results were consistent when evaluated among only non-breast cancer protocols.
  • Black, under-insured, and uninsured patients showed trends toward under-enrollment in clinical trials.

Whether rates this low are only applicable to patients in California who have previously received surgery as a first-line form of treatment for a solid tumor, or whether they are more broadly applicable across the whole of the USA, is not easy to establish. Some states — such as Delaware — have been claiming very high rates of enrollment in cancer trials in the past few years. (We have heard that as many as 20 percent of cancer patients in Delaware participate in clinical trials.) Clearly there is room for some improvement in California if that is the case … or even if the numbers in Delaware are significantly inflated.

The bottom line is that an insufficient number of cancer patients seems to be either aware of or  encouraged to participate in clinical trials. Furthermore, there is significant under-representation by age, by cancer stage, and tumor site.

As a society we need a clinical trials system with a real world perspective. Academic rigor is one thing, but designing and implementing trials that people actually want to participate in is crucial to an efficient clinical trials process. Let’s assume that Delaware is telling the truth, and that 20 percent of all cancer patients in that small state actually do participate in clinical trials. What are they doing right that has escaped the insights of their colleagues in California? After all, we know that enrollment in a clinical trial is actually the appropriate standard of care for large numbers of cancer patients (including some men with prostate cancer after first-line surgery).

Reuters has also commented on this story under the heading ‘ “Abysmal” participation in cancer trials.’

One Response

  1. Here’s the way options after recurrence following surgery for prostate cancer look to me and perhaps to a lot of us. The bottom line is that clinical trials need to offer at least as much likely benefit as these options.

    First, as research from Johns Hopkins has strongly indicated, many recurrences are so mild that follow-up medical steps are not needed. (The initial work, keying on PSA doubling time, Gleason of less than 8 versus 8 or higher, and recurrence to a PSA of 0.2 before 3 years or later, was by Freedland and others.)

    Second, many recurring patients in the remainder from the first situation, those who do need to see a more favorable PSA doubling time or other key characteristics, may be able to achieve that by simple lifestyle tactics. For instance, the UCLA (Pantuck) study showing a striking increase in PSA doubling time (or actual decreases in PSA) from 8 ounces of pomegranate juice, and a similar recent study by Johns Hopkins researchers using pomegranate extract, show clearly that some men can achieve the cancer control needed with such simple steps. (Perhaps mild medications such as the 5-alpha-reductase inhibitors will in the future prove to tip the scale to the good side for some men who are employing lifestyle tactics.)

    Third, many recurring patients who are not covered by the first two situations will be well covered by salvage radiation, possibly with supportive hormonal therapy.

    Fourth, as before in the first situation, some in the remnant of patients in the third situation who were not cured with salvage radiation will have recurrences too mild to merit further medical measures.

    Fifth, as before in the second situation, some patients in the group of patients whose post-salvage radiation recurrences are too aggressive to leave alone will be able to tame those recurrences by simple lifestyle tactics.

    Sixth, for those patients for whom the lifestyle tactics in the fifth situation were not sufficiently effective, modern androgen deprivation therapy (ADT) will offer a high probability of long-term control of the cancer. It appears a consensus is emerging that intermittent ADT is substantially better tolerated by patients and at least as effective at cancer control, with response to ADT indicating whether the patient is eligible for intermittent treatment. I am personally convinced that many of us will do best with triple ADT maintained in the off-therapy period with a 5-alpha-reductase inhibitor. Dr. Mark Scholz, medical co-author of “Invasion of the Prostate Snatchers,” has stated that it appears men on intermittent, maintained ADT3 will be able to successfully control their cancers for either about 10 to 11 years or indefinitely. That is credible to me based on what I’ve heard from fellow prostate cancer warriors on that regimen and on my own response to intermittent, maintained ADT3: I’m now in my third vacation period for a challenging case as I near the 12-year point. Unfortunately, drug companies have been reluctant to support trials of ADT3, which has a bearing on the clinical trial option.

    Isn’t the argument strong that a patient in situations 1 through 5 above would be well advised to avoid clinical trials unless the trial arms were all at least as promising as the indicated solution for those situations (no follow-up needed, lifestyle tactics, salvage radiation, post-salvage no follow-up, post-salvage lifestyle tactics)? At a minimum, the wise patient should be mindful of these well-documented and/or easily implemented and with personal effectiveness quickly verified options for recurrence (e.g., by lengthening of PSA doubling time). The patient should assess how a proposed clinical trial (all arms to which he might be assigned) would be at least as good. If it were me talking to a patient in the sixth situation, I would present the known evidence about intermittent, maintained ADT3 as well, but I recognize that the merits of that approach are still controversial, due to the absence of clinical trials. Frankly, I would be concerned for a patient in situation 6 who was put into a clinical trial that did not involve at least ADT3 or the option to move to ADT3 before his case involved a substantial risk of detectable metastatic disease. I believe those medical oncologists making extensive use of ADT3 in their practices would feel ethically bound to offer ADT3, based on the impressive success rates they have documented.

    This approach — favoring the solutions indicated for situations 1 through 6 — would reduce the likelihood that a patient would enter a clinical trial to test alternatives for these situations. The advancement of science would be slower, but is it not clear that the patient would be better off? I believe the patient is entitled to the approach that serves him best, even if that means that future patients may not gain from his participation in a clinical trial. I was offered several clinical trials shortly after I was diagnosed. The drugs involved were highly experimental and have not panned out. I consider myself profoundly fortunate that I pursued ADT3 instead, encouraged by a very clear sharp decline in PSA.

    If patients are beyond help from the approaches in situations 1 through 5 (1 through 6 for me and those who are convinced of the effectiveness of ADT), then clinical trials are entirely appropriate and participation should be fostered.

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