This news release reports the results of a phase 3 trial of a cancer treatment called vascular-targeted photodynamic therapy (VTP), which involves injecting a light-sensitive drug into the bloodstream and then activating it with a laser to destroy tumor tissue. Researchers in Europe randomized 413 men with low-risk prostate cancer, assigning half to VTP and half to the current standard of care, active surveillance, and tracked their progress over 24 months.
The news release reports quantified benefits and harms and mentions that the research was funded by a company that holds a commercial license for the therapy. However, it does not state the full extent of harms, offers no discussion of study limitations, and hypes the findings with speculative quotes, a faulty comparison with breast cancer treatment, and a patient anecdote that includes scary language.
This poorly done news release was also rehashed nearly verbatim by Reuters. We also reviewed that story, which earned one star.
Medical practice is evolving away from treating low-risk prostate cancer, in which the cancer is small and expected to grow very slowly. The current standard of care is active surveillance, in which no treatment is given and periodic tests are performed to see if the cancer is growing. For most men, treatment is never required or can be postponed for years without lowering the chance of a cure. Researchers in this study argue VTP is a “safe, effective treatment for low-risk, localized prostate cancer” and “might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy” on the off chance that their cancer were to grow and require more invasive measures. But in an accompanying editorial, Stephen Freedland, M.D., of Cedars-Sinai Medical Center, argues it’s “not readily apparent” who might benefit from VTP, which he says amounts to over-treatment for patients with low-risk disease and under-treatment for patients with aggressive cancers. A larger question is, are the financial costs and potential adverse effects of this therapy worth a marginal short-term improvement for patients who have a low risk? Any discussion of the merits of this potential treatment must address that uncertainty. While VTP apparently was derived from bacteria that thrive with little sunlight, that’s a property not shared by science.
There’s no discussion of the costs of either VTP or of active surveillance, the current standard of care for low-risk prostate cancers. Given that VTP is a new commercialized therapy involving both a drug and a device, it’s likely to be considerably more expensive than monitoring.
Furthermore, the study indicates that 75 of the 197 patients who started the therapy were retreated within 2 years. Because cancer was still being detected during follow up, this implies that these patients will need the same monitoring as those undergoing active surveillance.
The news release states that the study found that 49% of patients treated with VTP went into “complete remission” compared with 13.5% in the control group. It further states:
In the trial only 6% of patients treated with VTP needed radical therapy compared with 30% of patients in the control arm who were under active surveillance.
While it’s good to see some numbers, we have concerns about the “radical therapy” statistic and what it means, which we’ll address below in the “Evidence Quality” criterion.
We also call foul on a patient quoted in the release who says. “I’m now cancer-free with no side-effects and don’t have to worry about needing surgery in future.” Unless he has a crystal ball, there’s no way to know with certainty whether he’ll need surgery or not in the future.
Perhaps the biggest issue, however, is that the outcomes reported in the news release–and the study–are only surrogate markers. They are proxies for the things we care about like length of life and quality of life. The key question–which would take at least a decade to answer–is whether men undergoing initial VTP are less likely to die from prostate cancer than those opting for active surveillance. And the release doesn’t make this clear.
We’re also uncomfortable with the release’s description of patients achieving “complete remission,” a phrase that we’ve never seen used to describe prostate cancer treatments. All we know is that these men had no evidence of prostate cancer on repeat biopsy. However, biopsies sample only a small portion of the prostate and often miss areas of cancer. Using the phrase “complete remission” is likely to give readers a false sense of how beneficial this treatment really is.
The release states VTP “only caused short-term urinary and erectile problems which resolved within three months, and no significant side-effects remained after two years.” While it’s good that harms were mentioned, it’s a disservice to patients to downplay their impact with the word “only.”
Further, the news release does not give the proportion of patients on VTP who experience adverse events, which was 80 percent. Nor does it mention that 30 percent of VTP patients versus 10 percent of those in the active surveillance group had serious adverse events.
Finally, the news release glosses over the fact that over 1/3 of subjects needed repeat treatment within 2 years and that men undergoing VTP appear likely to need to be on the same monitoring protocol as those on active surveillance (meaning they will need biopsies, which carry risks). VTP and prostate biopsies can cause harms.
The news release describes the scope and methodology of the study, including the number of patients and treatment sites. But it does not discuss some important limitations described in the study, including the fact that more research is needed to determine the long-term efficacy of tissue-preserving therapies such as VTP in controlling prostate cancer.
As pointed out in the accompanying editorial, applying more rigorous criteria to define low-risk cancer would likely identify men who clearly would not benefit from any active treatment. Moreover, one of the outcomes reported in the release — the need for radical prostate surgery, which the researchers say is lower with VTP — is problematic because neither the release nor the article say how it was determined that additional treatment was needed. One reason that men switch from active surveillance to surgery is that they are uncomfortable not treating their cancer. In this study, the men in the intervention group may have been more comfortable not aggressively treating their cancer because they were getting the VTP. The cancer progression reported in this study is actually much higher than has been reported in other studies.
The news release contains an inflammatory quote from a patient who signed up for the trial because, he said, “Some men prefer to delay treatment, but I couldn’t live with the fear of the cancer spreading until it either couldn’t be treated or needed a treatment that would stop me living a normal life.” That’s one man’s take, certainly not representative of all men — and it exaggerates the risk of small prostate cancers.
Quotes from the investigator are also questionable. Active surveillance is described as monitoring and treating only “when” the cancer becomes more severe. The correct phrasing would be “if and when” the cancer progresses, because many of these cancers will not progress. Moreover, we are not still “commonly” removing or irradiating the whole prostate–studies have shown a marked increase in the uptake of active surveillance.
The news release states that the trial was funded by Steba Biotech, which holds the commercial license for the treatment. However, it does not mention that all of the study authors received compensation from Steba, and some also receive money from other biotech firms.
In some cases, the news release accurately compares VTP with the control, active surveillance. However, it also misleads readers by comparing VTP with aggressive treatment for higher-risk prostate cancer. For example, it states:
Radical therapy causes lifelong erectile problems and around one in five patients also suffer from incontinence. By contrast, VTP only caused short-term urinary and erectile problems which resolved within three months, and no significant side-effects remained after two years.
Moreover, the wording used by the release is misleading–radical therapy does not always cause lifelong erectile problems as suggested. Nerve-sparing procedures can preserve potency for a substantial proportion of patients.
But with respect to VTP, even short-term problems are unacceptable if the treatment is not actually necessary.
The news release passes the bar with this statement at the very end:
The VTP treatment is currently being reviewed by the European Medicines Agency (EMA), so it is likely to be a number of years before it can be offered to patients more widely.
The news release also quotes a researcher stating that the treatment’s implementation at 47 sites “without complication” indicates it’s “safe, efficient and relatively easy to scale up.” That’s an optimistic take but we’ll give the benefit of the doubt here.
The news release does not appear to overstate the novelty of this treatment. According to the research paper, “To our knowledge, our study is the first prospective comparative rial of the efficacy and safety of focal therapy and the first assessment of active surveillance for prostate cancer in a comparative setting.”
A researcher’s statement that VTP represents a “a huge leap forward for prostate cancer treatment” is overblown. Further, we don’t like that same researcher’s flawed comparison of VTP with advances in breast cancer treatment:
In 1975 almost everyone with breast cancer was given a radical mastectomy, but since then treatments have steadily improved and we now rarely need to remove the whole breast. In prostate cancer we are still commonly removing or irradiating the whole prostate, so the success of this new tissue-preserving treatment is welcome news indeed.
It remains to be seen whether VTP will “steadily improve” treatment for prostate cancer.
We also take issue with this data-free speculation from a researcher:
We can now pinpoint prostate cancers using MRI scans and targeted biopsies, allowing a much more targeted approach to diagnosis and treatment. This means we could accurately identify men who would benefit from VTP and deliver treatment more precisely to the tumour. With such an approach we should be able to achieve a significantly higher remission rate than in the trial and send nearly all low-risk localised prostate cancers into remission. We also hope that VTP will be effective against other types of cancer – the treatment was developed for prostate cancer because of the urgent need for new therapies, but it should be translatable to other solid cancers including breast and liver cancer.
We submit that the “urgent need” is to find tumor markers that better identify low-risk patients who do not need any treatment at all.