Principles of surgical oncology

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Contents

Introduction

Surgical resection of cancers remains the cornerstone of treatment for many types of cancers. Historically, surgery was the only effective form of cancer treatment, but developments in radiation therapy and chemotherapy have demanded that surgeons work with the other disciplines of medicine in order to achieve best results for the patient with cancer.

This type of interaction between the medical disciplines together with the supportive care groups required by cancer patients is defined as multidisciplinary care. It is now widely recognised that for optimal treatment of cancer a multidisciplinary team with the surgeon as part of this team is essential.

Surgery is effective treatment for cancer if the disease is localised. Defining the extent of the cancer before surgery has become much more accurate with modern imaging methods including computed tomography (CT), positron emission tomography (PET) scanning and high resolution ultrasound. The exploratory operation to determine the extent of disease, or attempting a ‘curative’ resection when the disease has already spread beyond the bounds of a ‘surgical’ cure, is not part of the modern surgical treatment of cancer. Oncological trained surgeons are now distinguished from more general surgeons because of the particular needs of the cancer patients.

Clinical trials are required to evaluate new treatments and treatment combinations. The struggle against the scourge of cancer has seen an explosion in basic research directed towards cancer. This academic element to cancer care is a constant feature as all those involved in cancer care endeavour to advance the understanding of the management of cancer patients.

These preceding paragraphs define the discipline of surgical oncology. In summary, surgical oncology is the involvement of a specialty trained surgeon as part of a multidisciplinary team program, the use of appropriate surgery in an adequately staged patient and the involvement of the surgeon in academic programs particularly involved with clinical trials.

The use of effective techniques in the operating theatre, the careful management of the patient undergoing surgery and supportive post-operative care are similar requirements to those of all other disciplines of surgery.

Communication with the patient and family, the obtaining of informed consent and the careful honest, realistic but where possible optimistic explanation of the results of surgery, are all matters of high importance to all surgical practice. However, the ability to talk sympathetically to cancer patients and their family is particularly important in the field of surgical oncology.

Multidisciplinary care

Surgeons need to understand the principles and practical consequences of the treatment offered by radiation oncologists, medical oncologists and the paramedical disciplines in order to be able to work in a team to treat cancer patients.

Radiation oncology

Ionising radiation is usually delivered to tumours as external beam therapy. This is generated by linear accelerators. Radiation kills living cells both by direct DNA damage and by the formation of free oxygen radicals in the cells. Free radical formation is the predominant effect and depends upon the level of oxygenation of the cell. Hypoxic areas of tumours are thus protected from the effects of radiation and large necrotic tumours will not respond well to this form of treatment.

When a linear accelerator is used to supply external beam therapy to a tumour, the patient goes through a series of planning exercises to accurately delineate the tumour and direct the radiation as accurately as possible to the tumour to minimise the impact on normal tissues. The linear accelerator is usually located in a large concrete bunker, often underground to provide protection to staff and patients.

An alternative method of administration of radiation is by using a local radiation source applied close to the tumour. This is known as brachytherapy. It is a highly effective form of therapy in tumours such as cervical cancer, other gynaecological cancers and prostate cancer.

Both normal and neoplastic cells are affected by radiation, so the dose which can be given in any situation is limited by the tolerance of the surrounding normal tissues. Tissues particularly at risk include the bone marrow and gastrointestinal tract, which contain rapidly dividing cells. The spinal cord is also at risk as it does not have repair mechanisms able to manage radiationinduced injury. However damage to DNA in cells from radiation can be repaired by a complex series of intracellular mechanisms. The normal tissues thus can recover from radiation provided the dose is not extreme, but malignant cells can also repair such damage. The actual dose of radiation (unit of measurement is a Grey) required to kill a particular tumour varies. Some cancers, for example Hodgkin's disease and cancer of cervix and some breast cancers, can be sterilised completely with acceptable degrees of damage to the surrounding tissues. Other cancers, for example melanoma and sarcoma, can rarely be eradicated using acceptable doses.

Fractionation of the dose of radiation over a period of time, by utilising daily low doses does provide better tumour response and less damage to normal structures than a single large dose.

The use of more modern methods of imaging and computerised dose planning allows for far more effective delivery of radiotherapy than in the past. The calculation of optimal doses and the delivery through new techniques, such as intensity modulated radiotherapy, has improved results and minimised side effects from radiotherapy.

The effectiveness of radiation treatment can be enhanced by the use of a radiation sensitiser. A commonly used sensitiser is 5 Fluorouracil® given by intravenous (i.v.) injection or by i.v. infusion.

Radiation may be delivered with curative intent, for example in treatment of seminoma of testis or as palliation for advanced or metastatic disease. A common use of radiation in this setting is for treatment of painful bony metastases, seen for example in lung cancer and prostate cancer. Effective symptom relief is often achieved with the use of radiation therapy.

Radiation therapy, often combined with chemotherapy, so called chemoradiation, may be used preoperatively (neoadjuvant therapy) or post-operatively (adjuvant therapy).

Neoadjuvant therapy prior to surgery is designed to reduce the bulk of a large primary tumour in order to improve the likelihood of successful surgical resection. This is now the standard of care in the management of locally advanced rectal cancers. Neoadjuvant therapy in this situation has been demonstrated to reduce the likelihood of local recurrence after surgery.

Post-operative adjuvant radiotherapy is also used when pre-operative therapy has not been given. As an example, this has also been shown to reduce postoperative rectal cancer recurrence particularly when positive glands are removed at the time of resection of the rectum.

There are particular benefits to giving the radiation therapy before surgery. These include the fact that the normal tissue planes allow better oxygenation of tissues without the post-operative damage where scarring and potentially hypoxic areas are left behind following surgery. It is also easier to define and localise the tumour to be irradiated without this scarring. This is associated with less damage to the normal tissues as the radiation can be applied very accurately to the tumour. Again, using the example of rectal cancer, preoperative localisation of the rectal cancer with MRI allows for accurate radiation doses to be given to the rectal tumour. Post-operatively however, the small bowel becomes adherent in the pelvis and thus can receive a significant degree of radiation damage because of its fixed position. Pre-operative treatment is better as the patient can be postured to remove the small bowel out of the pelvis, thus reducing small-intestinal radiation exposure.

Medical oncology

Medical oncologists use cytotoxic agents to modify tumour growth. The drugs interfere with cell division by a variety of methods and can be classified according to the site of action on the cell division process. Recently new classes of drugs have been developed as advances have occurred in the understanding of the molecular and genetic factors involved in cancer. Examples include angiogenesis inhibitors, EGF receptor blockers and most dramatic and widely used Imatinib (Glivec®), a Bcr-Abl protein kinase antagonist which blocks the binding site for ATP. It inhibits the growth of certain tumours, including gastrointestinal stromal tumour, and chronic myeloid leukaemia, with sometimes drastic effects.

Some cancers can be cured with chemotherapy alone. Testicular tumours and Hodgkin's disease are such examples. These are the exceptions however and for most solid tumours chemotherapy treatment produces a limited complete response or partial response.

Many randomised controlled clinical trials have demonstrated survival benefit from the use of chemotherapy even when cure cannot be obtained. Like radiation therapy, chemotherapy is given either as neoadjuvant therapy (i.e. pre-operatively), or postoperatively (adjuvant therapy), where it is used after a surgical resection. Post-operative adjuvant therapy is given where a complete resection has occurred but the potential for metastatic disease remains. Breast cancer and colon cancer are two cancers where landmark clinical trials have demonstrated significant improvement in survival with the use of a course of adjuvant chemotherapy after resection of the primary tumour and adjacent lymph nodes.

Chemotherapy does have significant side effects, particularly haematological and gastrointestinal, as the rapidly dividing cells in these areas are susceptible to the drugs. Neutropenia, thrombocytopenia, and diarrhoea and other gastrointestinal upsets are common side effects. Many of these symptoms can be ameliorated by medication.

Chemotherapy is usually given in cycles to reduce side effects and to improve tumour response by catching new clones of resistant cells as they redevelop after the initial cell kill in the primary tumour.

Supportive care

The holistic approach to the care of the cancer patient encompasses a range of supportive and coordinating services through the management phase of the illness. This is often delivered by a range of nursing and allied health professionals. Psychosocial support includes investigation and treatment of cancer patients by suitably trained nursing staff, social workers, psychologists and psychiatrists. Each discipline can offer some support depending on the problem faced by the cancer patient. A nurse coordinator often aids in the management of the patient. The use of such professionals has been shown to improve outcomes for cancer patients. The most extensively studied model is the breast care nurse who acts as a facilitator and informant for breast cancer patients. This type of support is likely to spread to the management of other cancer patients.

Surgeons treating cancer patients learn to recognise that they are members of a team rather than the sole arbiters of the patients' treatment programs.

Palliative care services

Modern palliative care programs are part of the services offered to cancer patients. These services include ambulatory and hospice programs for management of the end stages of life when attempts to cure or actively treat the cancer have ceased. Physical and psychological symptom control is an important part of modern multidisciplinary care. Palliative care physicians also help in pain control and symptom control in the earlier stages of the illness and thus broaden their influence in the journey of the patient with cancer.

Principles of surgery for malignant disease

The principles involve screening and diagnosis, assessment of the patient, staging of the extent of cancer, decision about treatment by multidisciplinary team, principles of operative surgical oncology, rehabilitation and follow-up. Each of these will be dealt with in turn.

Screening and diagnosis of malignant disease

Screening

Surgical resection has the potential to cure early or localised cancers which have not metastasised. In general early cancers equate with curability. For example, a malignant polyp in the colon is usually curable by surgery. However, this does not always hold true. Small breast cancers may metastasise early with cure not inevitable from surgical excision alone. However the principle of early diagnosis, or an early asymptomatic cancer, is accepted as the most effective way of reducing the mortality from cancer. Screening for cancer to detect early asymptomatic cancers is now commonplace.

For screening to be effective, the test must be able to detect a common cancer at a stage when it can be cured by treatment. The test must be sensitive, specific and acceptable to the public. It must also be offered to the population age at risk. For screening to be effective it must be introduced on a population basis. Screening of individuals by a doctor is known as case finding.

Controlled clinical trials of population screening have been carried out and do show survival benefit in a number of diseases. The most effective screening program has been cervical screening where, since its introduction, there has been a substantial fall in mortality from cervical cancer in all age groups. Similar less dramatic effect is seen with breast cancer screening by mammography, colon cancer screening using faecal occult blood testing and follow-up colonoscopy. Cancer of the stomach is screened for in Japan but the disease is now of low incidence in Western countries making screening not cost effective. Barrett's mucosa is common in Western countries but the incidence is not sufficient to make endoscopic screening for this condition effective. Lung cancer in high risk groups (heavy smokers), although an apparently attractive group for screening, has not been used in a general population program because it is not cost-effective or clinically useful using current technologies.

Surgeons are involved in screening programs performing endoscopies and biopsies (e.g. abnormal Barrett's mucosa), excising polyps from the colons at colonoscopy and biopsying mammographically detected breast lesions.

Diagnosis

A tissue diagnosis is essential prior to the creation of any management plan for a cancer patient. The consequences of many cancer treatments are so severe that only rarely can treatment be commenced without a pathological diagnosis. Tissue is obtained by fine needle aspiration, core biopsy or by excisional biopsy.

FINE NEEDLE ASPIRATION CYTOLOGY

Fine needle aspiration cytology (FNAC) and core biopsy can be done on an outpatient basis and provides a rapid diagnosis of accessible lesions such as breast lumps, head and neck lymph nodes and thyroid swellings. For less accessible lesions ultrasound guidance for the biopsy needle is necessary and commonly used. Core biopsies (Trucut®) can give a definite tissue specimen and can be performed in the clinic as well as by radiologists using ultrasound or CT radiological guidance. Internal lesions in for example the lung, peritoneal cavity or any solid organ can also be accessed by these methods.

Lymph glands or masses in the neck are a particular situation where a FNAC diagnosis allows for treatment planning which may involve a major neck dissection to remove the entire lymph node field. An incisional biopsy is not recommended as it may compromise the chance to achieve a satisfactory clearance of lymph nodes at a later date.

All of these techniques rely on the expertise of the pathologist to make a definite diagnosis on the basis of either the cytological characteristics of the tumour or more advanced pathological techniques, for example immunohistochemistry.

EXCISIONAL BIOPSY

Where a local mass or skin lesion can be completely excised without significant morbidity, excisional biopsy is the treatment of choice, removing the problem at the same time as making the diagnosis.

This technique is commonly used for skin lesions, particularly suspected squamous cell carcinoma, basal cell carcinoma and melanoma. Usually the procedure can be carried out under local anaesthetic in an outpatient theatre setting with minimal morbidity and discomfort.

HISTOPATHOLOGY

At times the histopathologist cannot accurately define the tissue of origin of a tumour deposit after excision. Many advanced histological techniques are now available to distinguish tumours from one another. For example, monoclonal antibodies against leucocyte antigen may help differentiate carcinoma from lymphomas. S100 antibody staining can distinguish melanoma from anaplastic carcinoma. More recently genomic techniques including array studies have been used to clarify the histological diagnosis of various tumours. Rarely a definite diagnosis cannot be made, particularly of the site of an anaplastic carcinoma. Clinical examinations and investigation have then to be performed to try and define the primary diagnosis, as the therapeutic plan will differ for different primary organ sites.

Assessment of the patient

An important early part of the assessment of a patient with cancer is to determine the health and fitness of the patient. Many cancer treatments are demanding on the physical and psychological resources of the patient. An idea of the ‘health’ of the patient can be gained from a simple clinical assessment, the Eastern Cooperative Oncology Group (ECOG) status. Patients who are ECOG 3 or lower will usually have a poor outcome from any treatment including major surgery.

All patients undergoing major surgery need assessment of the clinical status including, where appropriate, tests of cardiac function, for example scans and angiography if indicated, respiratory status by lung function tests and renal function tests including creatinine clearance.

Modern surgical oncology is required to be precise and accurate in resecting tumours where appropriate and be conducted with minimal morbidity and mortality. Pre-operative testing of the physical status of the patient is mandatory to obtain good results from major cancer surgery.

Staging of malignant disease

Accurate staging of the extent of disease is of great importance in formulating a treatment plan. Clinical stage is that defined by clinical examination and imaging of the patient. It is often not accurate but with the use of high quality CT and PET scanning the accuracy is improved. Pathological staging is that defined after excisional surgery by the anatomical pathologist. It is accurate in defining the extent of disease associated with a primary tumour. Small-volume or micrometastatic disease is not easily detected by any method of examination. The most commonly used staging system used is the TNM (tumour, nodes, metastases) system. The AJCC booklet describes theTNMstaging system for all cancers. Suffixes to the T, N, and M indicate the size of the tumour and presence or absence of nodal disease or metastases. For example, T2 N1 M0 indicates the stage of a tumour e.g. carcinoma of the colon where the tumour has spread into the muscularis propria but not through the wall of the colon where there are adjacent lymph nodes involved (N1) but no metastases detected (M0). The staging system is varied according to the primary site of the tumour.

Rectal cancers have a long-standing clinical and pathological staging system known as the Cuthbert- Dukes staging system. Dukes A is local disease in the rectum not invading muscularis propria; Dukes B, the tumour has extended through the wall of the bowel; and Dukes C, where there is lymph node involvement. Dukes D is when distant metastases are present. The Dukes system is commonly used alongside the TNM system.

Methods of clinical staging include radiological methods such as CT, MRI and ultrasound. Within the area of nuclear medicine are PET scanning and nuclear scanning generally (e.g. bone scanning). For intraabdominal tumours laparoscopy is an added staging method which detects occult disease.

Decision about treatment at the multidisciplinary conference

Armed with information about the diagnosis of the cancer, the extent of the disease, that is the clinical stage of the disease and the fitness of the patient, decisions can be made about the most appropriate treatment program. Ideally consultation with a multidisciplinary team occurs at this stage, however if the decision regarding surgery is straightforward, the multidisciplinary conference usually occurs after the surgery when a pathological stage has been determined. However many cancers require down-staging with radiotherapy or chemotherapy prior to surgery, and multidisciplinary consultations early are important to facilitate this process.

The provision of written information to the patient and family, with careful and repeated discussions, is necessary to ensure that the patient can give informed consent to any treatment plan offered. Patients have the right to refuse all or some of the treatment plan and they are encouraged to be part of the decision making process.

At this stage discussions regarding involvement in research projects, use of resected tissues and involvement in clinical trials need to be commenced.

Principles of operative surgical oncology

The technical issues in surgical oncology are not different from other surgical intervention. Open surgery, laparoscopic surgery, robotic surgery, ablative interventions and other technical interventions all have a place in modern surgical oncology. However some important oncological principles exist which must be followed by the surgeon for a satisfactory outcome.

Definition of curative surgery

Despite modern staging methods, occult tumour spread is still discovered by the surgeon, for example small-volume peritoneal disease or unsuspected nodal disease. Frozen section examination of the disease is necessary to confirm the diagnosis. So-called curative surgery is only performed when a total excision of all the tumour is possible. The primary tumour and the associated lymph node drainage fields are excised in continuity. A measure of the adequacy of the oncological surgical operation is demonstrated by the findings on pathological examination of the specimen. The operative specimens need to be correctly orientated by the surgeon to allow the pathologist to carefully examine and interpret the specimen given to him. The key issues are:

  • whether the margins of the specimen removed are clear of tumour
  • the total number of lymph nodes excised together with the number of involved lymph nodes.

Standards exist for the adequacy of the surgical excision to be assessed in many tumours.

Palliative surgery

Here the operation is performed to overcome some symptom-producing consequence of the tumour either by resection or bypass. This is to remove a potentially symptomatic lesion even though a cure is known to be impossible. Examples include the following:

  • In case of pyloric obstruction from an advanced cancer of the stomach, a gastrojejunostomy will provide good palliation of vomiting.
  • Resection of a bleeding cancer of the colon is justified even in the presence of metastases.

Many other examples exist. ‘Tailoring’ this type of surgery to the needs of the patient without undue morbidity or loss of quality of life is an important role for an oncological surgeon.

Margins of surgical excision

The degree to which normal tissues should be removed with the primary tumour is a subject constantly being researched. A universal rule is not possible to formulate. In general a margin of 2-5 cm is suggested. Particular examples follow:

  • For excision of melanomas the depth of excision is more important than the extent of surrounding skin. A margin of 2 cm usually suffices in contrast to the 5 cm previously practiced.
  • However for oesophageal resection the majority of the oesophagus needs to be resected because the tumour does spread up and down in the submucosal plane.
  • Soft tissue sarcomas may spread along aponeurotic planes so that complete excision requires the resection of the entire muscle group and fascial compartment to encompass this type of spread.
  • The recognition that spread of rectal cancer occurs into perirectal tissues has led to the use of the total mesorectal excision of the rectum to improve the completeness of resection.

The principle of complete local excision with an adequate margin is paramount in surgical oncology and it needs to be achieved in different ways depending on the type of tumour being resected.

Lymph node resection

Traditionally the draining lymph nodes from a primary tumour are excised with the local lesion. The main benefit of this removal is increased staging information, which will affect the decisions regarding post-operative adjuvant therapy. In some situations there may be a survival benefit from removal of early-involved lymph nodes. However prophylactic excision of uninvolved nodes does not provide a survival advantage to the patient and exposes the patient to increased morbidity from the node removal. An example is the prophylactic removal of groin lymph nodes (radical groin dissection), when these glands are not involved. This operation is nowadays not performed when the glands are clinically not involved as randomised controlled trials have shown that survival rates have not improved but the morbidity from the operation is significant. Poor skin healing and swelling of the affected leg are two such complications.

Rehabilitation

It is necessary to undertake rehabilitation of the cancer patient who has undergone major resectional surgery. This usually involves the allied health disciplines, part of the oncology team. The type and duration of the process will vary according to the type of tumour and surgery performed. Some examples are as follows.

  • Post head and neck surgery, for example laryngectomy, voice production can be learned by
  • development of oesophageal speech. Resection of part of the tongue will require re-education of speech.
  • Gastric cancer resection involving partial gastrectomy produces a major impact on the nutritional status of the patient. Dietetic support is required to reeducate the patient to a new balanced regular eating program.
  • Removal of large muscle groups or amputation will require physiotherapy and orthotic involvement to enable the patient to learn to live with the defect and walk or move as best possible.

The ability to adequately rehabilitate patients who have suffered significant disability as a result of the presence of the cancer and need for resection is critical in understanding the quality of life issues affecting cancer patients. As outcomes research becomes more common in assessing results of cancer treatment, there will be a better understanding of this important issue.

Follow-up of patient after initial treatment program

A program of follow-up is required for cancer patients after their initial treatment. This is for two main reasons. This is to observe the patient and investigate when appropriate to detect recurrent disease, which can then be treated effectively. By definition this is only likely to be useful to the patient when strong effective postoperative therapies are available which will have a real impact on the control of cancer. Where no such therapy exists intensive follow-up is not recommended.

  • One example of this is the early detection of liver metastases after colorectal cancer treatment. Survival gains are possible when appropriately staged patients with liver metastases are successfully resected.
  • Breast cancer follow-up is also intense because of the variety of therapies which are available to control disease. However strong proof from intensive followup of cancer patients impacting on survival is lacking for breast cancer as for most tumours.
  • Detection of asymptomatic but untreatable recurrent cancer does not do the patient any favour.
  • Regular follow-up provides the opportunity to manage the adjuvant therapy programs which are offered to many patients for 6–12 months following the initial treatment for the cancer.

Secondly the follow-up provides an opportunity to support the patient through the psychological upsets which accompany the diagnosis and treatment of cancer. Increasingly it is recognised that severe psychological morbidity exists in cancer patients who have been treated. This exists even if the cancer is apparently cured. This has led to a developing interest in the concept of survivorship, that is understanding the needs of the ‘cured’ cancer patients. Psychosocial support is essential for many cancer patients and is best delivered in the setting of multidisciplinary care.

Clinical trials and research

Clinical research is essential to evaluate the new and previously untested treatments. Surgeons are involved in a number of ways:

  • Provision of tissue for tissue banking. This is a fast growing program throughout the world. The provision of fresh tissues for genetic studies is of paramount importance to the understanding of malignant disease. Highly organised tissue banking programs are now being put in place. These involve the collection and storage of tissues under standardised conditions, the collection of other material, for example blood and bone marrow, and most important and perhaps most difficult, the collection of accurate clinical data to be evaluated alongside the laboratory data. Surgeons provide the tissues and have the chance to be involved in the projects that interest them and so should keep a careful watch on the ethical issues which abound in this complex area of clinical and laboratory research.
  • Surgeons are involved in clinical trials. Surgeons recruit patients for clinical trials which allocate patients to treatment programs directed towards the first stages of treatment of cancer. The recruiter for randomised clinical trials must be able to demonstrate equipoise in relation to the arms of the study and be able to assure the patient that there is no reason why he or she should not enter the trial, as current knowledge suggests that both treatment arms, although different from each other, have equal efficacy.

Patients involved in clinical trials are generally thought to receive better care than those outside the trial. This relates to the level of care and attention given to the patient, which is engendered by the demands of the trial. An increase in the clinical trials recruitment is a major ambition of the surgical oncology movement.

Conclusion

The principles of surgical oncology can be applied to many of the systemic practices of surgery. In simple terms the surgeon operating on cancer patients in the 21st century must have some understanding of the malignant process, be prepared to work as part of a team and offer multidisciplinary care, communicate well with a very concerned sometimes desperate group of patients, operate with a high level of skill and perform an adequate cancer operation, help the patient rehabilitate from the treatment and finally be prepared to be involved in the advancing area of surgical science as applied to cancer patients. As God knows, surgeons cannot cure all cancers on their own.
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