Surgery

Surgery is a major pillar of conventional oncology and the most direct approach for treating cancer. It involves a procedure where a highly-skilled surgeon physically removes cancer from the body. In certain situations, surgery is all that is required to eliminate cancer, but it may also be combined with other therapies, before (neoadjuvant), during (concurrent), or after (adjuvant) the operation [1]. Whether surgery is a suitable treatment option depends on a number of factors such as cancer type, size of tumor, location, whether it has spread (stage of disease), and a patient’s overall health [2].

In cancer care, surgery may be preventive (removal of precancerous tissue), diagnostic (such as biopsy to determine treatment approach), curative (intention to cure), supportive (enhances other treatments), palliative (relieves symptoms), and reconstructive (cosmetic) [3]. Anesthesia keeps you from feeling pain during surgery, which can be local (numbs small area of body), regional (numbs whole part of body) or general (complete loss of feeling and consciousness) [1].

Historically, the rule of thumb of the cancer surgeon was that increasingly radical surgery would enhance cure rates [4]. In more recent years, it has come to light that minimally invasive techniques can significantly reduce the detrimental effects of surgery and improve results [4]. Preservation of form, function, and quality of life is the new golden rule [4]. Surgery is often a crucial part of cancer treatment, but unfortunately it can also have serious side effects, including fuelling cancer growth [5]. A shift in awareness appears to be occuring in the scientific community around the systemic nature of cancer as a disease and the need for a more holistic and individualized perspective on cancer treatment [6].

More than a quarter of people worldwide will ultimately be affected by cancer and surgical removal remains the primary approach to try to cure and control most solid cancers [5]. Research shows that surgery, under certain circumstances, increases survival rates and improves outcomes for patients with various cancer types. However, while surgery can save or extend life, it has also been known for a long time that operations can accelerate tumor recurrence and spread of disease [5]. Both experimental and clinical evidence support the concept that, paradoxically, surgery can increase the development of metastases (secondary tumors) [5]. It is therefore often required for patients to include supportive therapies (rather than surgery alone) to maximize the chance of a successful outcome.

Historical Perspective

Surgery is the oldest form of cancer intervention dating back thousands of years [4]. It has always been, and remains, the primary treatment modality for solid cancerous tumors [7]. Prior to the introduction of anesthesia and antiseptics around 150 years ago, only the brave, desperate, or ill-informed went under the knife [4]. Cure rates were low and risk of death was high [4]. However, over the last decades, surgical techniques, safety and efficacy, has drastically improved [7].

The first recorded references of surgical procedures for cancer date back to around 1600 BC [8].** Ancient Egyptian medical texts such as The Edwin Smith Papyrus and Ebers Papyrus describe cauterization techniques (use of heat) to destroy tumors [8]. **In the 5th century BC, Hippocrates, a famous Greek physician, made observations about breast cancer surgery [8]. However, he cautioned against surgical procedures to treat cancer and proclaimed that it would shorten overall survival [8]. Hippocrates believed that cancer was a systemic (humoral) disease that affects the whole body rather than a specific organ or tissue; and that a cure for cancer can only be achieved by rebalancing the whole system through a holistic approach [6]. His insights still offer lessons for modern medicine and holistic practitioners alike [6].

In the 18th century, John Hunter, who is considered to be the father of surgery, introduced many new concepts into medicine and the field of oncology [8]. Hunter believed that cancer was a localized process, and in certain circumstances, could be treated by surgical removal [8]. However, he was still highly concerned about the potential negative effects on the constitution as a whole [8]. He stressed the importance of total removal of tumors and outlined potential areas of lymphatic spread [8].

It was not until the middle of the 19th century and the advent of general anesthesia that major advances were made in the surgical treatment of cancer [8]. In 1842, Crawford Long first used general anesthesia [8]. Shortly after, in 1846, William Morten publicly demonstrated the effectiveness of general anesthesia for major surgery at the Massachusetts General Hospital [8]. In 1890, William Halsted performed the first radical mastectomy (removal of entire breast and surrounding lymph nodes) for breast cancer [9]. The procedure increased the long-term survival of breast cancer patients from around 5-10% to more than 40% [8]. The technique he outlined for the operation survived as the classical surgical approach to breast cancer until recent times [8].

The past 50 years have seen a paradigm shift in the field of surgical oncology with major technological advances, improved techniques, minimally invasive procedures, and daring challenges to established dogmas [4] [7]. Today, cancer surgeries have become routine, safe and effective [4]. Further technological advances are set to increase safety and efficacy, while novel adjuvant treatments and therapies should continue to improve outcomes and long-term survival [4].

Research

According to The Lancet Oncology Commission surgery is an essential part of cancer care in all countries around the world [3]. Of the 15.2 million new cancer cases worldwide in 2015, over 80% were reported to be in need of at least one operation (some several). By 2030, it is estimated that annually 45 million surgical procedures will be required worldwide [3].

A 2005 study evaluated survival rates of women with breast cancer who underwent surgery compared to those who refused surgery [10]. The study included 5,339 patients recorded in the Geneva Cancer Registry between 1975 and 2000. The results revealed that women who refused surgery were more than twice as likely to die from breast cancer compared with operated women. The authors concluded that women who refuse surgery have a strongly impaired survival and that this information may help patients make more informed decisions.

A 2006 study on women with breast cancer and liver metastases (secondary tumors) showed that even for patients with metastatic disease surgery may improve outcomes [11]. The study included 85 patients with breast cancer that had spread to the liver and were treated with hepatic resection (removal of part of liver). The results showed that surgery provided a significant survival benefit for patients compared to medical treatment alone.

A 2015 study comparing the effectiveness of breast-conserving surgery (BCS) and mastectomy revealed that BCS with radiotherapy (RT) led to better survival than mastectomy alone or with RT [12]. The study included 160,880 patients with non-metastatic breast cancers and monitored survival over a period of 8 years. Mastectomy is significantly more invasive than BCS + RT. The authors concluded that patients should be made aware that a minimally-invasive approach can actually produce better outcomes.

Women are increasingly surviving breast cancer. However, a 2019 review explains that up to 90% experience unexpected long-term side effects as a result of cancer surgery [13]. Breast cancer survivors may suffer serious adverse effects that can negatively affect quality of life [13]. Long-term physical changes include chronic pain, phantom breast pain, axillary web syndrome, and lymphedema [13]. Additionally, some patients may experience decreased strength, reduced aerobic capacity, mobility issues, fatigue, and cognitive dysfunction. Emotional and psychosocial changes include depression, anxiety, concerns about body image, and issues with sexuality [13].

A 1992 study on lung cancer surgery survival rates found that patients with stage 1 non-small-cell lung cancer (NSCLC) who underwent surgery survived significantly longer than those who did not have surgery [12]. Around 70 percent of patients who received surgery survived more than five years, while only two unoperated patients survived more than 5 years. The results indicate the importance of early detection and timely surgery for lung cancer.

Paradoxically, research also shows that surgery can accelerate spread of disease and increase the likelihood of recurrences. A 2012 study including 1,506 patients with NSCLC evaluated the effect of lung cancer surgery on the development of metastases [15].** The study revealed a surge in disease recurrence around nine months after surgery followed by two smaller peaks after the second and fourth years. The results support the hypothesis that there are systemic micrometastases (microscopic secondary tumors) that lay dormant around the body [15]. **The removal of a primary tumor may in turn accelerate the growth of new tumors at secondary sites [15].

There is actually growing scientific evidence that supports the concept that surgical removal of a primary tumor can actually spur the development of new tumors and accelerate growth of residual and micrometastatic disease [5] [6] [16]. A 2017 review article explains that surgery increases shedding of cancer cells into the circulation, suppresses antitumor immunity (allowing circulating cells to survive), upregulates adhesion molecules in target organs, induces changes in tissues making them more susceptible to invasion by cancer cells, recruits immune cells that can entrap tumor cells, and enhances migration of cancer cells to new locations in the body [5].

Furthermore, a 2011 study on the effects of prostate cancer surgery and chemotherapy on metastatic disease progression revealed 4 important findings [16]. The researchers found that for all 12 patients studied: (1) inception of the first metastasis occurred when the primary tumor was undetectable; (2) inception of all metastases occurred before the start of treatment; (3) the rate of metastasis shedding remained the same regardless of the size of the primary tumor and was only minimally affected by treatment; and most importantly, (4) surgery can cause a dramatic increase (by dozens or hundred times for most patients) in the growth of metastases [16].

These findings support a growing awareness and mounting scientific evidence that cancer is a systemic disease rather than a localized mutation that needs to be eradicated [6]. Therefore, some researchers are pushing for a radical change in cancer care that takes more of a holistic view of each patient’s specific situation [6]. The research also highlights the importance of systemic treatments and reveals the potential shortcomings of surgery as a primary response to treating cancer.

Potential Applications

There are many different types of surgery, which vary depending on the purpose of the operation, the location of the tumor, amount of tissue to be removed, and also, the preferences of the patient [17]. Surgery can be open or minimally invasive. Minimally invasive surgery is less of a physical insult to the body and therefore takes less time for the patient to recover.

• In open surgery, the surgeon makes a single large incision to remove the entire tumor, some surrounding tissue and possibly nearby lymph nodes.
• In minimally invasive surgery, the surgeon makes multiple small incisions and inserts a camera along with special surgical tools to remove the tumor.

Surgery is a primary treatment for many different types of cancer. It is most effective for solid tumors that are contained in one specific area of the body [17]. Surgery is not suitable for all cancer types and situations. Whether surgery will be the best treatment option depends on a range of factors including [2]:

• Cancer type
• Size of tumor
• Stage of disease (if has spread or not)
• Location of cancer
• Age
• Overall health

Sometimes surgery is not possible due to the location of the tumor and proximity to delicate tissues or vital body parts such as major arteries or blood vessels [2]. If cancer has spread to multiple locations in the body, systemic treatments may be required instead, or in conjunction with surgery. There are several types of surgery that can benefit cancer patients. Some are used alone while others are carried out in combination with other therapies. Types of cancer surgery include [18]:

• Curative surgery: Complete removal of tumor or cancerous tissue from the body when it is localized in a specific area in the body. This can be a primary treatment, but can also be combined with other treatments before (neoadjuvant) or after (adjuvant) an operation.
• Preventive surgery: Removal of precancerous tissue that may develop into a malignant tumor such as polyps in the colon.
• Diagnostic surgery: Removal of tissue for testing or evaluation to confirm a diagnosis, determine the type of cancer or stage of disease.
• Staging surgery: A camera is inserted into the body through a small incision and tissue samples may be taken from various sites.
• Debulking surgery: Partial removal of a tumor in circumstances when complete removal would damage vital organs. Generally combined with other treatments such as chemotherapy or radiation.
• Palliative surgery: To alleviate symptoms and relieve discomfort, but not cure cancer.
• Supportive surgery: To help other cancer treatments work better such as the insertion of a port or catheter for chemotherapy.
• Restorative surgery: To help restore a patient’s appearance. It is often used as a follow-up to curative surgery. For example, breast reconstruction surgery after the removal of a tumor.

According to the conventional paradigm in modern medicine and current allopathic understanding of cancer, it is believed that cancer is initiated when one, or a few, cells acquire certain irreversible cancer-causing mutations (amongst other hallmark factors), which disrupt cell cycle controls, programmed cell death regulation, and promote proliferation and invasion of cancer cells [16]. Within this conceptual framework, cancer is considered like an alien entity that progresses through specific stages, which are classified by the extent of its spread around the body (local, regional and distant) [16]. Metastases (secondary tumors) are considered to be independently growing cancers that develop from cancerous cells, which are shed by the primary tumor and take root at various secondary sites [16]. The war-like approach to treatment is to eliminate all cancer cells, as early as possible, and the more aggressive the treatment of the primary tumor the better the outcomes are expected to be [16].

A new paradigm of understanding regarding the nature of cancer as a disease has recently begun to emerge based on more than 100 years of extensive scientific research [16] [19] [20]. According to the new paradigm, cancer is considered to be an organ-like entity that exists in a dynamic homeostatic relationship with its surrounding environment, which can either fuel or suppress disease progression [16]. A key aspect of this balance is the dormancy of microscopic secondary tumors at various sites around the body and a large number of cancer cells in the blood and lymph circulation [16]. Primary and secondary tumors engage in a complex biochemical interaction that generally results in the suppression of smaller tumors by larger tumors. In addition, the seeding of secondary tumors appears to occur long before the primary cancer is actually clinically detectable, which makes cancer a systemic disease, even at very early subclinical stages [16].

Furthermore, wound healing processes following surgery of the primary tumor may promote the growth of secondary tumors and angiogenesis (formation of new blood vessels to fuel cancer growth) [16].** **Trauma and inflammation have long been correlated with accelerated tumor growth [5]. The innate immune system is activated systemically and locally as a result of surgical tissue trauma, which precipitates a complex inflammatory response. The inflammation is fundamental to the healing process and elimination of pathogens. However, the systemic and local inflammatory response in tissues also appears to provide fertile ground for circulating tumor cells to invade, and then subsequently fuels their growth [5].

Under normal conditions, metastasis is an inefficient process and the majority of cancer cells reaching circulation are quickly destroyed [5]. However, surgical trauma to the tissues elicits a cascade of inflammation that has the potential to capture cancer cells and support metastatic tumor growth [5]. Proinflammatory cytokines (signaling molecules that control inflammation) such as IL1 and TNFα have been shown to stimulate the adhesion of cancer cells to secondary sites around the body [5]. Furthermore, manipulation of the tumor during surgery has been shown to result in increased shedding of tumor cells into the blood and lymphatic circulation [5]. In fact, it can result in a 10-fold increase (or more) in circulating tumor cells. Additionally, the trauma of surgery can suppress immune function. It has been shown to diminish natural killer cell and macrophage activity, which are directly responsible for controlling and eliminating cancerous cells [5].

As a new understanding of cancer progression emerges, some researchers are calling for a paradigm shift in cancer care [6]. Rather than waging war on cancer as an invading organism that must be rapidly and brutally destroyed, some are advising to reframe cancer as a systemic disease and organ-like structure that functions within a complex system [6]. From this standpoint, cancer as a disease cannot necessarily be surgically separated from the host organism and is more likely caused by homeostatic imbalance and systemic inflammation among other factors [6].

Therefore, to legitimately cure cancer (rather than artificially induce remission for a period of time), treatment strategies must be based on holistic principles that take into account the physical, mental, and social wellbeing of the entire organism, that is, a human being (not just a patient) [6].

Risk and Side Effects

Cancer surgery side effects and risks depend very much on the type of operation. In general, most operations come with a risk of [21]:

• Pain: It is very common to experience pain after an operation, but this can often be well managed with pain medication.
• Infection: It is possible to get an infection after surgery, but appropriate wound care can reduce the risk of complications.
• Loss of organ function: Surgery may require the complete or partial removal of an organ such as a kidney or lung. For some operations, such as removal of a kidney, it may not cause significant problems. On the other hand, the removal of a lung could make it harder to breathe.
• Fatigue: After surgery, you may experience low energy and difficulty concentrating. This is quite normal and resolves after some time.
• Bleeding: All operations come with a risk of bleeding.
• Blood clots: Recovering from surgery puts you at a higher risk of blood clots. The risk is small, but can be very serious. Movement and blood-thinning medications may be advised to reduce the risk.
• Bowel and bladder function disturbances: After surgery it is common to have difficulty with bowel movements and urination, but this generally resolves after a few days.

Risk is inherently involved in any surgery. There is always a possibility of anesthesia complications and side effects. Nevertheless, through advances in medical technology surgery has become ever safer and more reliable [22]. In many cases, the positive effects on survival outweigh the potential risks [22]. However, the risk of any surgical procedure depends greatly on each patient’s specific situation and overall health.