I thought about this extensively when deciding which oncological career to pursue. I won't rehash the radiation-will-become-irrelevant arguments that we've all heard. But I did give them serious consideration, and I envision an different future based on the following points of reasoning. I'm just about to start intern year, so I am by no means yet an oncologist, so don't flame me if some details are inaccurate... unless they show a flaw in my broader logic, in which case, let's discuss!
1) How good do I think targeted therapies will get? Based on what they currently do, I think they'll get good at control... really good maybe. I believe targeted therapies for solid malignancies perhaps in conjunction with "personalized medicine" will allow medications to shrink and slow the growth of tumors. I don't think there are many examples of targeted therapies curing solid malignancy. They hold them at bay. They buy time. I imagine they'll buy more time in the future. Time to pursue a definitive approach. Surgery or radiation. So as med onc advances evolve and reliably halt the growth of tumors including metastatic disease, I believe the relevance of well-targeted (ie having benefited from all this lovely physics research) will be increasingly important in eradicating disease that medications have held in check. I'm less optimistic that any cocktail of targeted therapies is going to kill all cancer cells... it's just now how these agents work.
2) Investment in radiobiology is a promising way to make a systemic therapy (chemo, targeted, etc.) locally active and cancer specific. Radiation causes a dramatic change in cellular function. It alters transcription of myriad genes and activates numerous cell survival and cell death effectors. These processes occur differently in malignant versus normal cells. I view this as presenting a unique opportunity to use radiation to promote sensitivity to various potential targeted therapeutics. "Radiosensitization" is often discussed... I sorta view it the other way. Use radiation to activate survival pathways that we can attack with targeted therapies. I don't see the field as being particularly far along with this idea, despite its long history in the literature and being essentially the topic of research for all bench scientists in rad onc. Cancer is flipping hard to cure if you can't cut it out or zap it good. This difficulty is solidly grounded in the many ways cancer cells evolve and overcome seemingly slam dunk attempts at eradication. I believe there's a bit in The Emperor of All Maladies that discusses the discovery of Ras in 1982 and the foretold end of cancer within a few years as soon as we develop an inhibitor. Well. Here we are with no Ras inhibitors, and really no targeted therapies that cure solid tumors despite a dramatic increase in knowledge of how cancer works and agents that hit many oncogenes. This is not to sound pessimistic. It's to point out that the lack of fruit borne of attempts to use radiation and medical therapies together well is not surprising, and it's not too far out of step with advances in pure medical oncology. I do believe the field itself has to invest in this heavily. I'm not entirely sold on the idea that rad onc will become irrelevant without harnessing radiobiology, but for the sake of moving the field forward and improving patient outcomes, this is a no brainer.
3) Despite dramatic potential that I believe will be realized, I believe the potential of all medical therapy for cancer (chemo, targeted, immuno) is inherently limited by human and cancer biology. Put simply, they're very similar, and any "cancer specific" agent (say a nice cocktail of agents targeting the "driving" mutations of a malignancy) selects for resistance. It's like antibiotics... except instead of starting with evolutionarily distant cellular machinery to target, we're targeting our own stuff... this means we will be forever locked in a battle between off target effects and development of resistance. In general I don't believe in betting against future possibilities (with science!), but there are a limited number of small molecules, a limited number of targets, and a lot of incredibly complicated biology to unravel that argue strongly against counting on medical agents as the future whole answer to cancer. This relative pessimism for medical oncology as the absolute cure is simply recognition for what I believe: Cancer is multidisciplinary... local therapy with surgery and radiation are going to be important for the future of cancer care and will co-evolve with medical advances.
4) I agree that increasing doses ad infinitum and improving accuracy have been hugely important for the field, but are also approaching their limits. Ultra high dose requires precise delivery. These are excellent capabilities to have, but there are many instances where the strength of radiation lies in our ability to give it to a larger area for disease that may not be as localized as the dose we can give. So, since we can't give huge doses to lots of normal tissue, I believe we gotta figure out how to make radiation/targeted therapies work better with less radiation (see point 2).
5) Maybe my thinking on this is flawed, and this is kinda an evolution of point 4, but if radiation were to get as targeted as a surgeon's scalpel, are we giving up a hidden strength of radiation: the inexactness of its targetability? Meaning if I could zap a prostate and just a prostate, then I miss "the margins". Something I've thought about a bit, and I wonder if anyone else has thoughts on that concept.
Just some thoughts on these topics. As I was told on the interview trail (by the chair at the program to which I matched, btw): it's clear that I'm a novice in this field. I'm good with that, and I'm incredibly excited to join a field that I believe has a very bright future.
Cheers.
