Tiresias: Scorched Earth versus Precision

"…precision is next to godliness "

Samuel Beckett

My friends,

Tiresias is not particularly fond of military metaphors in medicine, but given the times we live in, the military metaphor in cancer treatment seems quite apt. Cancer treatment has a long history and for most of the history the treatment has done more harm than good, caused more suffering than relief, more deaths than lives saved. In the 20^th, century when some treatment began to be of some benefit to the patient, it was at huge cost in terms of suffering and disability to the patient. Most of the treatments were very radical, untargeted, and very destructive. To use military metaphors, it was, and largely still is, “carpet-bombing” or “scorched earth”. Or to Peter Arnett, reporting from the Vietnam War, quoting a Major after a military action, "we had to destroy the village in order to save it.” This has been, and Tiresias is afraid, often still is the nature of cancer treatment. There have of course been some improvements in the last twenty to thirty years. Super radical heroic commando surgery, blunderbuss widefield untargeted high dose radiation and highly systemically toxic chemotherapy, which destroyed normal tissue and resulted in chronic pain and suffering have definitely improved in the last 30 years. Super radical mastectomy, in breast cancer, has been gradually modified till now most patients undergo just lumpectomies. The excision of half the chest musculature ribs and all other structures has finally given way to somewhat targeted surgery. But with this comes with the new problem of incomplete excision, failure of margin detection and of leaving behind cancer cells. Chemotherapy and radiotherapy have also become more targeted, and though better targeted and better dosed, are by their very nature a form of “localised scorch earth” therapy. There has to be a better way. And there is. The better way in precision in diagnosis, and precision at the time of surgery, precision and targeted treatment of cancer cells, and precision in cellular level with real-time digital histopathology using Optiscan’s Confocal Laser Endomicroscopy (CLE).

Tiresias would like to illustrate this with an example, a summarised example of a not uncommon cancer, Cancer of the Urinary Bladder. Tiresias is of an age in whose peer group, cancers are common, and discussions of cancers form a common subject of table and café talk. Of the recent period several of his friends have been diagnosed with cancer of the bladder, and Tiresias has watched these friends undergo the diagnosis, treatment, and surveillance for bladder cancer. For his friends not familiar with bladder cancer, the best analogy would be to consider bladder cancer would be to think of it as skin cancer, but just located in the “skin of the bladder”. So, most skin cancers or precancers are seen early and either frozen with liquid nitrogen or locally. Lack of in-vivo microscopy makes the adequacy of this treatment and subsequent surveillance largely hit and miss. It is similar, though a lot more complicated, with cancer of bladder. Bladder cancer usually presents with blood in the urine. The urologist, via cystoscopy, performs a macroscopic inspection looking for the site of the bleeding. If something is seen it is cut out and sent off for histopathology. The pathology results come back with several weeks. The pathologist has looked at this bit of tissue, and adjudges whether there are cancer cells there, and makes a judgement if there is a margin of normal tissue, and thus that the cancer has been wholly removed. This is at best wishful thinking. At the time of the first cystoscopy, the urologist cannot tell any of this and cannot tell if there are cancer cells left in the bladder, if there are isolated cancer cells away from the lesion if the cancer has invaded through or all is clear. If there is cancer left behind then further surgery localised can be done, again blind, not being able to see the cancer cells. Even if there are no evidence of invasion on the conventional histopathology, further treatment is undertaken, because everybody understands that the histopathologist cannot comment on what cells may be left behind in the bladder to proliferate. There is no precision at all in this next stage of treatment. This truly “carpet bombing” of the bladder, and literally leaves a “scorched earth”. It consists repeated monthly administration of BCG, a vaccine for tuberculosis and leprosy. It is administered through the catheter and left in the bladder for several hours, causing an acute inflammation of the bladder, and local and systemic symptoms of a urinary tract infection. In terms of our skin cancer analogy, this would be like after you've had your skin cancer excised or burnt off, covering the entire skin with a bacterial solution to cause most excruciating inflamed red burning rash of the whole skin to cause peeling of the whole skin to remove any unseen cancer cells, which may not be there at all. This is then repeated monthly thereafter to kill off and prevent recurrence of the cancer, or to cause inflammation which will “burn” the remaining cancer cells, as well as the whole surface layer of normal bladder mucosa. In terms of the” scorched earth” metaphor, let us imagine that your farm has been found to have had a single plant of toxic a noxious weed, let us say Box Poison. Rather than seeking the individual plants or having a precision targeted the treatment, one sets fire the whole farm on fire, burning everything to ashes, and then repeatedly burning as it starts to regenerate. There must be a better way and there is.

At this stage Optiscan is concentrating on malignant brain tumour, oral cancer diagnosis and treatment, and breast cancer surgery margin detection and post-lumpectomy surgical histopathology. Optiscan in conjunction with Pentax had developed, an FDA approved GI endo-microscope, on hold since the GFC and the takeover of Pentax by Hoya. Many other cancers, including my friends’ bladder cancer will come. Optiscan real-time 3-D digital confocal endo-microscope, with AI assistance and new targeted markers will stop the carpet-bombing scorching of the patient and bring in a new era of precise real time diagnosis and precision therapy. And it can’t come soon enough.