The oldest known use of surgery to treat cancer dates back to approximately 1600 BC in ancient Egypt. Of course, surgery today is far more humane than in those early days, thanks to the development of highly sophisticated surgical tools and procedures, as well as anesthesia, sterilization (antisepsis), and antibiotics.

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Mainstream oncologists view surgery as the best first treatment option for most early-stage tumors. If the tumor is small and slow-growing, it may never recur after the operation. Surgical treatment is also beneficial for removing large localized tumors as this reduces the tumor burden and helps prevent further tumor growth. For these large tumors, however, it is often necessary to remove excessive amounts of normal tissue as well, including parts of organs or even whole organs and potential sites of metastases.

In recent decades, improvements in screening practices and surgical techniques have significantly expanded the indications for the surgical treatment of cancer.  Modern approaches include new methods of conservative surgery, reconstructive surgery, laser surgery and microsurgery. The range of reconstructive surgery, which restores both structure and function of resected organs, is constantly expanding.

Nevertheless, surgical procedures are unjustified in the following cases:

  • SurgeryWhen the tumor cannot be completely removed because it has invaded vital structures or organs (e.g., brain tumors)
  • When the surgery becomes excessively traumatic, as in laryngeal cancer (which affects speaking and swallowing)
  • When the surgical approach is complicated by the tumor existing in an inaccessible location

There are different complications of surgery, some of which may become lethal. These include cardiovascular and respiratory disturbances, acute myocardial infarction (heart attack), pulmonary thromboembolism, and occasionally pleurisy. Another important group of complications is wound infections, which carry a high risk of mortality.

Some patients may refuse surgery based on the stage of the tumor, usually because of having a poor medical condition. Thus, patients can benefit from nutritional and lifestyle modifications prior to the operation, in order to strengthen the body beforehand.  In addition, careful assessment of potential dysfunctions of body systems is often recommended.

 

How Photodynamic Therapy Can Enhance Surgery

Photodynamic Therapy, or PDT, is often a better option than surgery when it comes to certain skin cancers (in particular, superficial basal cell carcinoma) because the light-based approach will not damage the skin or other structures. Surgery, on the other hand, can result in substantial morbidity, often leaving the skin scarred and damaged. PDT also has better cosmetic results in the context of skin cancer treatment. But the argument that PDT is the ideal alternative to surgery goes far beyond the cosmetic level.

With targeted photodynamic treatment methods, you can accomplish the same outcome as that accomplished by surgery, yet avoid various problems (e.g., immune suppression and morbidity) that may result from surgery.  When tumors are treated using PDT, PIT, or laserthermia, a process is set in motion that triggers the steady destruction of the cells within the tumor, primarily through various cell-death processes.  At the same time, the blood vessel supply to the tumor is greatly reduced, and consequently many tumor cells begin to die off through the process known as necrosis.

Other tumor cells undergo a kind of programmed cell death or cell suicide (apoptosis), while still others die as a result of being broken down or “digested” by their own enzymes (autophagy). Of these three types of cell death, it is necrosis that seems most critical to attracting the immune cells that will ultimately help eliminate the tumor.

Now, as a tumor starts to break down, it releases proteins called tumor antigens, which eventually are transported to cells of the immune system called dendritic cells. The dendritic cells take in these antigens, and then present the antigens to other parts of the immune system. This sets the stage for possibly alerting the entire immune system to the fact that cancer is present. However, the dendritic cells will not carry out this essential role unless certain other factors, called “danger signals” or “Danger-Associated Molecular Pattern” molecules (DAMPS), are also present. These signals are released in the process of photodynamic treatment.

In summary, even though PDT attacks the tumor directly, its more important effects may in fact be indirect—that is, educating the immune system to recognize and eliminate any microscopic clusters of cancer cells (micrometastases) that have moved to other parts of the body. Those clusters provide the seeds for growing metastases in the future.

Particularly when PDT is combined with other immune-enhancing strategies, its overall effects are not limited to breaking down the tumor, but also to controlling cancer that has spread to other parts of the body. By supporting the body’s ability to eliminate micrometastases, we can help prevent the progression of malignant disease to a more advanced and lethal form.

 

A Possible Future Strategy

Given the potentially adverse effects of cancer surgery, an argument could be made for using it more selectively or in a more limited fashion.  We now know that not all early-stage cancers require surgical treatment. Many breast and prostate tumors, for example, either remain dormant or regress and disappear on their own. These tumors would never develop into an aggressive disease, and thus many thousands of people go through unnecessary surgery every year, thanks mostly  to screening practices that detect those early-stage tumors.  The difficulty is determining which tumors are harmless and which tumors are likely to become aggressive.

A possible strategy in the future would be to postpone surgery and instead try PDT.  This would have to be done with your oncologist’s consent, based on a careful assessment of your tumor status.  Ideally, the tumor would be very small and you would have to be considered “low risk”, based on various considerations such as a low tumor grade (which generally predicts a less aggressive cancer).  Assuming that you, the patient, are monitored on a regular basis with scans and/or tumor marker measurements, you could then try undergoing PDT in order to cause the slow yet inexorable destruction of the tumor.

Another plausible strategy would be to use surgery in a limited or conservative way, to remove the bulk of the tumor.  You would then use PDT to eliminate any residual disease, including any cancer cells in the vicinity (or around the tumor margin) that are invisible to the surgeon’s eye.  This strategy has been proposed by Dr. Clemens Lowik, who heads the Optical Molecular Imaging Group at Erasmus Medical Center in Rotterdam, the Netherlands.

Dr. Clemens has successfully used this method in test animals.  His ingenious idea is to surgically remove the tumor, then stick a light down in the gap or indentation where the tumor had been previously.  The light then activates that photosensitizer that has accumulated in any cancer cells remaining in the vicinity of the surgical site, and this photoactivation triggers the destruction of those remaining cancer cells.

Of course, many tumors need to be surgically removed for specific situations.  Brain tumors, for example, may continue growing and invading the normal brain structures; such tumors may benefit from the Fluorescence-Guided Surgery (FGS) approach. Other tumors may benefit from the more gradual approach offered by PDT.

One might reasonably speculate that if a tumor takes many years to develop, then we should be similarly slow and deliberate in its eradication. By gradually dissolving the tumor using immuno-PDT, or breaking it down with classical PDT, there may be a greater likelihood of totally eliminating the disease and achieving better long-term remissions.

Keep in mind that we are not by any means rejecting surgery as a treatment option. Surgery still plays a particularly critical role for cases involving large tumors (debulking, removing the bulk of the disease) or those in which a vital organ is being impinged upon, perhaps compromising one’s ability to function normally.

Nevertheless, there may be many situations for which PDT as well as Immuno-PDT may be sufficient, particularly given the fact that the treatment also harnesses the anti-cancer immune defenses even as it’s breaking down the tumor. As we mentioned above, a key focus of the photodynamic approach to cancer focuses on “educating” or retraining the immune system so that a recurrence in the future is far less likely.

PDT is unique among other approved therapeutic approaches in its ability to support anti-cancer immunity for the entire body.   This awareness has helped foster growing interest in two promising modalities based on PDT, notably photoimmunotherapy (PIT) and PDT-based cancer vaccines. Though the lion’s share of scientific attention has focused on PDT, there is increasing research interest in these other forms of targeted light-based therapy and how they can complement PDT as well as other treatment approaches.

 

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