CHRISTUS Trinity Mother Frances Health System

Steven Curley

A diagnosis of cancer is still fraught with fear and uncertainty for patients and their family members. There have been remarkable advances in the past two decades in cancer genetics, biomarkers, immunotherapy, and other areas of translational research. The role of the microbiome in cancer causation and in response to cancer treatments is better understood and is being actively investigated further. Unfortunately, there were still over 600,000 deaths from cancer in the United States in 2022, and this number will expand as the size of our population grows and the number of people living beyond 65 years of age increases. Cancer is still a disease that disproportionately affects older patients, but there have been alarming trends noticed recently with large numbers of younger patients developing several types of cancer. The worrisome trend for cancer onset at younger ages just led the United States Preventative Services Task Force (USPSTF) to recommend changing the guideline to begin breast cancer screening with mammography at age 40. A decade ago, the age was 50, and a few years ago this was reduced to individuals 45 years old. Similarly, several professional societies now recommend the onset of screening colonoscopy to detect premalignant polyps or colorectal cancer to begin at 45 years of age rather than the prior standard at age 50.

There are several factors associated with cancer being the second most common cause of mortality among Americans. First and foremost is Americans; too many people smoke cigarettes, drink alcohol in excess, are obese, do not exercise regularly, and contract infectious disease agents that cause cancer like hepatitis B (HBV) or C (HCV) virus or human papillomavirus (HPV). A significant portion of our population makes lifestyle choices that increase the risk of cancer.  Another issue is irregular or poor access to healthcare for conversations about cancer screening and prevention. In more affluent urban and suburban areas, up to 60 percent of eligible individuals received age-appropriate cancer screening with mammography, colonoscopy, stool DNA testing, or Pap smears. Conversely, in rural or poor urban areas and among uninsured or underinsured individuals, screening rates fall below 20 percent. Overall cancer screening rates in the US fell to 21 percent during the COVID-19 pandemic. As a result, there has been an increase in the diagnosis of more advanced-stage cancers in the past two years. Cancer survival probabilities are directly related to the cancer stage at diagnosis. Thus, finding more early-stage cancers that can be treated with definitive surgery, ionizing radiation, chemotherapy, immunotherapy, or multidisciplinary combinations are more likely to result in long-term survival. Most Importantly, for most types of human cancer, standard diagnostic screening blood, imaging, or procedure-based studies are not available.

Hopefully, the absence of screening tests for almost all cancer types will cease to be problematic. The development of multi-cancer early detection (MCED) technology to screen for mutated pieces of cancer-specific DNA or proteins (biomarkers) promises to make the detection of cancer quick and simple with a single blood test. These blood tests are currently undergoing large-scale clinical validation studies in the U.S. and other countries. I foresee a time in the next decade where an annual MCED test will be drawn in potentially all Americans and those with cancer detected in the blood tests will be referred for appropriate diagnostic studies and cancer stageand location-dependent therapy. More early-stage diagnoses should result from broad application of MCED technology. This will produce improved long-term cancer survival rates. The significant problem of Americans increasing their risk to develop cancer based on their behaviors and choices is a more daunting public health, education, and political issue that will not be discussed further in this piece.

Imaging technology has also improved markedly in recent years. Dual-energy multi-detector computed tomography (CT), advanced magnetic resonance imaging (MRI) systems, and improved positron emission tomography (PET) hardware and software will permit more accurate cancer diagnosis and staging of disease, detection of primary cancers, earlier detection of cancer recurrence, and more accurate evaluation of the success of cancer therapies. There are several important technological advances in CT imaging including photon-counting detector systems. These systems provide clinicians with far more detailed, high-quality images and the ability to produce image reconstruction to evaluate tumor location in association with critical anatomic structures. Spatial resolution is also improved, and new CT imaging programs use AI and deep learning algorithms to reduce image noise, limit radiation dose, and allow the injection of lower volumes of contrast agents. MRI advances include stronger imaging gradients, enhanced receiver coil arrays, digital receiver technology, faster and more powerful reconstruction computers, and faster image acquisition times. It is now possible to obtain multi-contrast MR images from a single acquisition scan. PET has improved with advanced reconstruction algorithms, integration of AI-based reconstruction to enhance imaging clarity and allow detection of smaller tumors, identification of numerous novel radioisotope tracers to improve detection accuracy and assess treatment response, and development of high-density silicon photomultipliers to detect smaller malignant lesions. State-of-the-art imaging equipment will enhance the detection of metastatic disease, provide more accurate cancer staging information, improve assessment of treatment response to radiation therapy, chemotherapy, and immunotherapy, and aid in detecting early-stage malignant disease in patients who have a potential cancer diagnosis based on MCED testing.

Nanotechnology has been touted as an avenue for exploration to improve cancer detection and therapy. Nanoparticles made from a variety of materials have shown great promise as improved imaging contrast agents, as cytoprotective agents in normal non-malignant tissue during ionizing radiation, and as drug delivery vectors or agents that are intrinsically cytotoxic in cancer cells. A potential advantage of nano-material delivery of cytotoxic drugs is a reduction in normal tissue toxicities, which led to the approval of Nab-paclitaxel used to treat lung, ovarian, breast, and pancreatic cancer, as well as Kaposi sarcoma. Gold nanoparticles have demonstrated cytotoxicity against pancreatic and liver cancers in preclinical studies with no significant toxicity, but this must be confirmed in human clinical trials. Generally, nanoparticle-based drug delivery may improve the pharmacokinetic profile of anti-cancer drugs, enhance the delivery and retention of drugs in the tumor microenvironment, improve tumor-specific targeting, and reduce side effects to the patient. Numerous nanomaterial formulations are in clinical trials and these physico-chemically unique compounds are very promising to improve diagnostic and therapeutic efficacy in cancer patients.

" Nanotechnology has been touted as an avenue for exploration to improve cancer detection and therapy "

Historically, cancer treatment has been invasive and toxic to patients with considerable short-and long-term consequences and implications. Patients' quality of life can be adversely impacted during and for years after treatment with ionizing radiation, cytotoxic chemotherapy, immunotherapy, or major surgical procedures. Cancer patients desire and hope for successful cancer treatment, but frequently do not recognize the long-term effects of standard therapies. Surgery is the ultimately invasive anti-cancer treatment, and open surgical procedures can be lengthy, associated with not insignificant risk for mortality or complications, produce severe pain and protracted recovery periods, and often result in major changes in physiologic function or deformity. Robotic surgery is now being used more frequently every year to treat cancers in a variety of sites in the body. Robotic operations do require a learning curve for surgical practitioners, but once adept, these operations can be achieved through a series of small incisions that produce less pain and lead to decreased length of hospital stay and overall recovery time. Multiple studies have demonstrated oncologic equivalency with robotic compared to open surgical approaches to treat cancer. Advances in three-dimensional real-time visualization and haptic feedback, along with development of different robotic systems in a competitive marketplace should increase the experience with minimally invasive robotic surgery to treat cancer throughout the body. Surgery times will decrease with increased surgeon utilization experience.

Even minimally invasive surgical procedures usually require general anesthesia and are associated with post-procedure pain and potential complications. The ultimate direction in effective cancer treatment should be to develop non-invasive, minimal, or non-toxic treatment options. Focused, pulsed ultrasound microbubble destruction of solid tumors is becoming available to treat primary and metastatic liver cancers, and will soon be used to treat kidney, pancreatic, prostate, breast, thyroid, and skin cancers. This novel approach is entirely non-invasive and has caused minimal or no side effects or symptoms in treated patients. This technology has the added benefit of potentially enhancing the presentation of cancer antigens to the immune system to produce an abscopal effect with the killing of subclinical metastatic cancer deposits in lymph nodes or other organs. Patient-specific vaccine development using non-thermally destroyed cancer tissue should be effective using this treatment approach. Investigation of numerous other frequencies of non-ionizing radiation in the electromagnetic spectrum are ongoing in basic science and preclinical studies, all to be non-invasive, minimally toxic, not associated with long-term side effects, and to be used when appropriate with existing available multidisciplinary cancer treatments to improve destruction of primary malignancies, metastatic foci, and improving long-term treatment success rates while maintaining a better quality of life for cancer survivors.

The next decade holds immense potential for major strides in improving the detection of early-stage cancer throughout the body, enhancing the accuracy and utility of diagnostic imaging equipment, developing patient-specific anti-cancer therapies, and realizing the goal to create more effective and less invasive treatments with reduced toxicities and consequences for patients. The personal physical, emotional, and financial impact of a cancer diagnosis is profound, and the socioeconomic cost to human society is staggering. Improving the probability of meaningful long-term patient survival while reducing toxicities and side effects is a lofty goal for researchers and clinicians involved in cancer care, but one we must pursue with vigor!