Disclosures: Raghavan reports no relevant financial disclosures.
November 25, 2020
5 min read

Out of the dark age

Disclosures: Raghavan reports no relevant financial disclosures.
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On Oct. 25, 2016, HemOnc Today published an editorial titled “Animal Farm, 1984 and The Hunger Games,” which warned members of the electorate to be thoughtful about their imminent decisions and predicted a time of dystopia, contingent on the outcome.

Who could have predicted how prophetic these words were, with a scenario in which political centrists were silenced, physicians and scientists were accused of corruption and dishonesty, and our nation fell prey to a pandemic that killed a quarter of a million of its citizens?

In this year’s historic election, there was (hopefully) a return to the center, a resumption of respect for scientific principles and real evidence, and a new focus on the use of validated medical concepts to overcome disease.

Derek Raghavan, MD, PhD, FACP, FRACP, FASCO
Derek Raghavan

At a sociopolitical level, one can only beseech the political leaders on both sides to create rapprochement to regain the essence of these UNITED States of America. A feature that gave me some hope was the unequivocal evidence of widespread use of facial masking in the cross-nation celebrations when the election results became known, perhaps a new acknowledgement of the reality of scientific evidence about how to protect against COVID-19.

‘An extraordinary time of change’

As I write this editorial in a reflective mood, I should note that (in company with my friend and colleague, John Sweetenham, MD) I will relinquish my role as chief medical editor of HemOnc Today in January, after a run of 6 years.

It has been an extraordinary time of change in cancer medicine, beyond the sociopolitical environment. Although I believe it is important for influential physicians to take a role in social responsibility, and my editorials have done so, I see no reason again to review the political excesses of this time.

However, it is worth considering the changes in oncology since John and I took on our roles in 2014.

From a clinical and scientific standpoint, several key trends have emerged. The increasing understanding of targeted therapies, focused on the genes that drive cancer, has been a game changer. Once validated in second- or third-line contexts, many of these agents have now found their way into front-line use, and this often seems to produce major changes in survival.

The battle of the PD-1/PD-L1 interface — with checkpoint inhibition having application in malignant melanoma and renal cell carcinoma, and now apparently being meaningfully applied in front-line treatment of metastatic bladder cancer, lung cancer and other malignancies — is a real step forward, notwithstanding occasional reports that are too premature for credibility. Many other targeted agents, predicated on clearly defined molecular science, have been introduced into our armamentarium.

Not everything is proven progress. One result that has hit the racing news has been the observation that one of the checkpoint inhibitors, when added as an adjuvant after standard induction chemotherapy for metastatic bladder cancer, may increase survival substantially. At first glance it seems like a breakthrough, but it probably needs some extra work, with clarification of the nature of salvage treatments and follow-up in each arm of the randomized trial (and perhaps a confirmatory study with the same or other agents) before we assume that a new standard has been created.

Powerful randomized trials have shown that second- and third-generation androgen-blocking therapies, when added to the front line, and perhaps as adjuvant therapy, for prostate cancer also seem to have increased survival by periods of months to years (rather than days to weeks). The potential for men with prostate cancer to receive their androgen deprivation therapy in tablet form rather than via uncomfortable abdominal injections will certainly improve quality of life.

In the domain of hematologic malignancy, there seems little doubt that chimeric antigen receptor T-cell therapy is a breakthrough, and seems to be having a much more sensible introduction than some of the early work in bone marrow transplantation, showing that we learn from our errors and excesses.

Nobody has jumped onto CAR-T for breast cancer, although cautious and structured early trials are in progress, and perhaps more interestingly in other solid tumors (kidney cancer, melanoma) where the biology of the disease may lend itself to this type of therapy. The durable responses to CAR-T in lymphoma, myeloma and some leukemias are producing apparently true increments in survival. Hopefully the promising data in relapsed lymphoma will hold up.

Costs and equity

Two other very important domains are not focused purely on therapy.

The long-overdue recognition of the pain caused to patients and their families by the costs of treatment (so-called fiscal toxicity) is finally translating into action. The early work of a group led by Mark J. Ratain, MD, in Chicago — focused on measuring the problem and then taking active pharmacologic steps to alter treatment schedules and doses to ameliorate cost without reduced efficacy — is now being extended widely.

Although this approach is certainly crucial, it is also easily in the hands of every oncologist to address cost — for example, the simple act of prognosticating accurately and honestly, and discussing with patients the likely financial consequences of noncurative treatment and expected chance and length of survival, could make vast differences in the pattern of expectation and also the costs encountered.

Another domain of great importance is equity in treatment.

It must be more than a decade since Otis W. Brawley, MD, and I moved the ASCO task force on health disparities toward actually doing things to improve outcomes in underserved populations. However, as recently as this month, reports have documented the persistence of inferior outcomes for a range of cancers. This is simply unacceptable.

I believe that the published work of my team at Levine Cancer Institute, which has shown true equity of outcomes in the early diagnosis of lung cancer using a mobile CT scanning unit among uninsured and underinsured minority and rural populations, and equal outcomes among wealthy white and poor Black patients with lymphoma and myeloma, should be the paradigms of the future. Our preliminary data indicate that nurse navigation, with a focus on the needs of the underserved and a commitment to action rather than analysis, is a key component of this success.

Hopefully, under the presidency of Lori J. Pierce, MD, ASCO will take this issue up several notches and define an effective set of paradigms for true equity of cancer care worldwide. The cop-out that nationalized medicine fixes the problem is a similar fantasy to some medical concepts that have emerged from Washington, D.C., during the pandemic.

COVID-19’s toll on cancer

Finally, a story not yet written is the likely impact of COVID-19 on cancer cure rates.

Similar to during the 2008 financial crisis, we are seeing delayed presentations and a greater proportion of patients with advanced disease at diagnosis. Screening programs were initially halted for fear of exchanging occasional early diagnosis for increased risk for COVID-19 infection. Although the medical profession has moved past that, the population at large is not so sure, and we need to redouble our efforts to demonstrate safety in screening programs and the hazards of delayed presentation. Perhaps a new federal government will partner with the reputable medical organizations to become effective in disease management again.

Maybe the “hunger games” are over, and we can return to civilized life, effective and thoughtful bipartisan political activity, and a focus on the dangers that face us — COVID-19, global warming, unrestricted firearms and cancer.

There is much to do in the next few years and so much potential if it is done well.

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