CANCER TREATMENT

Principles of cancer treatment by surgery

Malcolm Reed FRCS

while others are treated in Cancer Centres and Cancer Units (e.g. breast, colorectal). The quality of the evidence is questionable, but it is widely accepted that specialist teams dealing with larger caseloads provide optimal care for most cancer patients. In addition to increasing expertise of team members, specialization and centralization results in the most efficient use of resources. This advantage must be balanced by the inconvenience for patients and carers travelling greater distances and the potential for deskilling and demotivating staff in Cancer Units no longer contributing to the treatment of certain categories of patients. The effect of these changes on surgical services has yet to be realized.

Surgery has been the cornerstone of treatment of patients with solid cancers for more than 100 years. For most of this time, there have been few changes in the technical aspects of surgery, with more or less radical procedures gaining or losing favour periodically. Recently, there has been a resurgence of interest in a more radical, anatomical approach, combined with increasingly complex procedures to preserve function or appearance. The increasing adaptation of radical surgery for recurrent and metastatic disease is also extending the role of surgery in cancer treatment. Traditionally, general surgeons provided the service for a wide range of patients with cancer. Subspecialization in general surgery (see Black, CROSS REFERENCES) started to appear during the 1980s and early 1990s. The publication of the CalmanHine report provided a major impetus to subspecialization into separate disciplines (e.g. breast, gastrointestinal tract (upper and lower), hepatopancreatobiliary). Some of these subspecialties deal almost exclusively with surgery for malignancy (e.g. breast), while others contain a substantial proportion of patients with non-malignant disease who may present with almost identical symptoms. Services have been extensively reconfigured to meet the needs of symptomatic patients who are found to have cancer. Initiatives in the UK (e.g. two-week rule for initial appointment, fast-track diagnostic clinics) are designed to streamline the pathway for those patients recognized by their GPs to be at high risk of malignancy. These patients must now begin definitive treatment within 62 days of referral. Paradoxically, this may delay the assessment and diagnosis of patients with malignancy whose presentation is not regarded as suspicious, and future initiatives must streamline access to treatment for all patients found to have cancer, regardless of the referral route. This review focuses on services in the UK.

Role of surgery in cancer treatment

Surgery in cancer diagnosis Improvements in diagnostic imaging, cytology and interpretation of wide-bore needle biopsies (core biopsies) have markedly reduced the need for open biopsies and diagnostic surgery. Image-guided core biopsy using ultrasound or CT is common and permits accurate diagnosis and treatment planning. Biopsies most centres use core biopsy for the diagnosis of malignancy because much more information can be gained from a core biopsy compared to fine-needle aspiration cytology. Core biopsy can reliably diagnose invasive disease, whereas cytology cannot distinguish invasive from non-invasive malignancy. Estimation of the status of the oestrogen receptor can be done on breast core biopsies, as can the identification of tumour type; tumour grade may be less reliably ascertained by this technique. Patients presenting with enlarged cervical lymph nodes are frequently referred to general surgeons who may carry out an excision biopsy as the initial investigation; this practice should not be used. A needle biopsy may help distinguish those patients with lymphoma from those with secondary epithelial neoplasia. Excision biopsy for the accurate diagnosis of lymphoma may be indicated after consultation with a haematological oncologist. Patients with suspected malignancy of the upper aerodigestive tract should be cared for by a surgeon with a specialist interest in malignancies of the head and neck. Poorly planned excision biopsies of metastatic nodes from malignancies of the upper aerodigestive tract are associated with an increased rate of failure of local control after further surgery. Laparoscopy is used in diagnosis and staging of intra-abdominal malignancy and can dramatically reduce the rate of open and close laparotomy. Curative surgery Early detection of cancer: the most important factor determining the likelihood of cure for patients with cancer is the stage of the disease at presentation. The early detection of cancer depends on a number of factors, including: public education and awareness access to and accuracy of diagnostic services in primary and secondary care introduction of effective screening programmes (Figure 1). Screening programmes a major feature of the NHS Breast Screening programme is the rigorous audit and quality assurance that has been in place since its inception. This resulted in the performance of individual surgeons being compared to standards
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Organization of cancer services

A major configuration of services for patients with solid cancers was initiated after the publication of the CalmanHine report; this fundamentally affected the way surgeons worked and trained. Multidisciplinary teams ensure that patients are treated by recognized specialists in accordance with accredited evidence-based guidelines. These guidelines (typically produced by the National Institute for Clinical Exellence) define how and where patients should be treated. This has resulted in centralized surgical services for many forms of cancer (e.g. upper gastrointestinal tract, hepatobiliary, urological, some gynaecological malignancies)

Malcolm Reed is a Professor of Surgical Oncology at the Academic Surgical Oncology Unit, Royal Hallamshire Hospital, Sheffield, UK.

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Prerequisites for a successful screening programme

The disease should be curable and early detection should increase the chance of cure The diagnostic test should be acceptable to the target population The disease should be sufficiently common The screening test should have acceptable sensitivity and specificity Resources (skills and facilities) should be available to allow implementation for the entire target population

and targets. Areas of weakness such as the quality of axillary node surgery were identified early in the programme and there has been a steady improvement in performance in this area. Several of the targets have been raised in response to improved performance. The method of quality assurance used in the screening programme has been introduced for patients with symptomatic breast disease and similar models are in place for other malignancies as part of peer review of Cancer Centres and Cancer Units. Plans are well advanced for the introduction of programmes for the early detection of colorectal carcinoma based on studies confirming the efficacy of colonic support screening of the asymptomatic population (see Scholefield and Whynes, CROSS REFERENCES). Many clinicians run ad hoc screening programmes for patients with a family history of malignancy, such as breast or colorectal cancer, based on the well-recognized increased risk to individuals with a number of close relatives affected by these conditions. There is no conclusive evidence that inclusion in such programmes results in a reduction of mortality, but evidence from a number of audits of family history clinics in breast cancer suggest that such programmes can detect disease at an earlier stage and at a greater incidence than would be expected. Attempts to launch a national controlled trial of screening for those with a family history of breast cancer have been unsuccessful. Screening in other groups of patients at high risk of malignancy (e.g. ulcerative colitis, Barretts oesophagus) have not shown a reduced mortality from the associated malignancy. Studies of endoscopic screening of patients with Barretts oesophagus have indicated that this may result in detection of oesophageal cancer at an earlier stage, when it is more likely to be curable by surgery. Staging: the introduction of preoperative treatments such as chemotherapy (see page 66) and radiotherapy (see page 62) for patients with local disease of borderline operability, and alternative methods of palliation for those with incurable metastatic disease, have led to the recognition of the importance of preoperative staging. For instance, it was previously common practice not to investigate patients with colorectal cancer for liver metastases because the primary tumour required excision and therefore management would not be altered. This approach failed to recognize the devastating effect of being told that metastatic disease had been diagnosed at an operation where the patient was hoping for cure. The introduction of alternatives for palliation (e.g. endoscopic stenting) has resulted in meaningful alternative choices for
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patients, and therefore staging is essential. The role of preoperative radiotherapy and chemotherapy in rectal and oesophageal cancer is rapidly increasing. Swedish studies of preoperative radiotherapy in rectal cancer indicate that local recurrence rates can be reduced dramatically, but this results in a local recurrence rate only equivalent to the best that can be achieved by surgery alone (about 5%). Staging systems based on clinical observation alone (e.g. traditional TNM, Manchester staging for breast cancer) are becoming obsolete due to improvements in imaging and pathological staging systems. The local staging of most cancers is now based entirely on histological features, whereas the presence or absence of distant metastases is dependent on imaging. The influence of histopathological assessment in clinical outcomes is subtle and needs to be recognized when interpreting and comparing trends in cancer survival. This effect, known as stage migration can result in apparent improved survival for patients due to more accurate staging. For example, a more rigorous examination of the status of lymph nodes in patients with rectal cancer results in more patients being allocated into the Dukes C group; this results in an improved survival for the patients classified as Dukes B, due to the exclusion of some patients with more advanced disease. The inclusion of patients with minimal involvement of the lymph nodes in the Dukes C group also results in improved overall survival for these patients. Likewise, the introduction of more sophisticated techniques for evaluating distant metastases (e.g. improved resolution of ultrasound scanner, use of CT or MRI) increases the detection of minimal metastatic disease, with a similar effect on the survival figures. The detection of micro-metastases in lymph nodes with the aid of immunohistochemistry or molecular pathology techniques has led to the identification of patients with minimal metastatic disease. Prognosis and adjuvant treatment for these patients, who typically have breast cancer, is controversial, with no clear evidence of the effect of this finding on outcome. In terms of cancer outcomes, the most important statistic is overall disease-specific mortality in the population. This epidemiological data depend on the completeness and accuracy of cancer registration and death certification. Postmortem studies of the accuracy of death certification indicate that a significant proportion of clinical diagnoses of cause of death are inaccurate and epidemiological data on disease outcomes can also be flawed. Curative surgery for primary cancer: there are widespread variations in the surgical management of individual types of cancer. This is shown by the different mastectomy rates for breast cancer, and the variation in the formation of permanent stomas in patients with rectal cancer. Certain principles can be applied to the surgical treatment of cancer with curative intent (Figure 2). Surgery and adjuvant therapy: the advent of multidisciplinary team meetings for common cancers ensures that the involvement of clinical and medical oncologists is introduced early into the care of cancer patients, before surgery and again at the time of review of the histopathological results of surgery. This has facilitated adjuvant therapies before and after definitive surgery. There has been a major increase in the use of adjuvant chemotherapy in cancer of the breast and gastrointestinal tract, as well as radiotherapy in rectal cancer, and a combination of chemotherapy and radiotherapy in oesophageal cancer.

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Surgical treatment of cancer with curative intent

Patient care should be undertaken by a multidisciplinary team comprising surgeons, pathologists, radiologists, oncologists and specialist nurses. Macroscopic clearance of disease should be achieved wherever possible. The surgery is classified as palliative if this is not achieved. Resection margins should be wide if there is a danger of microscopic infiltration. Dissection of lymph nodes does not improve survival, but may yield valuable information for prognosis and selection of adjuvant therapy in patients with several types of cancer. Sentinel node biopsy permits the restriction of axillary surgery in breast cancer and, potentially, melanoma patients to those with proven nodal disease. This reduces the unnecessary morbidity associated with negative lymph node clearance while ensuring good local control in patients with node involvements. Unnecessary surgery in patients with inoperable disease should be avoided by adequate and accurate preoperative staging. Alternatives to surgery in patients with incurable disease should be actively considered. 2

Postoperative care: early postoperative morbidity resulting from the complications of surgery and suboptimal management in the perioperative period contributes to the mortality associated with cancer treatment. A significant improvement in outcome may be seen if this problem could be reduced, but this would require: an increase in the availability of HDU and ICU facilities a more active preoperative optimization of patients before major surgery an increased awareness of the importance of postoperative fluid balance and the early detection of serious complications (e.g. anastomotic breakdown). Significant resources are required to improve these aspects of patient care. Studies have indicated that a substantial proportion of patients admitted as emergencies with colorectal cancer have been referred as elective patients or are in the process of being worked up for surgery; this group of emergency patients carry a high risk of mortality compared to patients admitted for elective surgery. The introduction of targets to accelerate the referral and diagnostic process and the potential effect of screening could have a substantial effect on the mortality associated with surgery for colorectal cancer; a similar situation may exist with cancer of the upper gastrointestinal tract and oesophagus. The realization of this benefit depends on the accuracy of the referral and rapid diagnosis of malignancy. Curative surgery for metastasis: in some circumstances, patients with metastatic disease can undergo further surgery with a reasonable prospect for cure. For instance, hepatic resection for liver metastases from colorectal cancer has become widespread. The traditional indications have been challenged and, in many
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Cancer Centres, the indications for surgery are purely technical, whereby the most patients with resectable disease may be offered such treatment. In experienced hands, this procedure is associated with a low morbidity and mortality. This is an area of rapid expansion in service demand given the frequency of colorectal cancer in the population and the fact that >50% will develop liver metastases. A further area where resection of metastases is possible and can result in long-term survival is sarcoma surgery, where surgery of lung metastases has been practised for some time. Sarcomas are rare tumours and this type of surgery is uncommon. The possibility of further curative surgery for diseases such as colorectal cancer and sarcoma has greatly altered the way these patients are followed up. It is routine practice for patients with colorectal cancer to have ultrasound of the liver and regular monitoring of the concentration of carcinoembryonic antigen in their serum. Patients with soft-tissue sarcomas should be followed-up in dedicated clinics where imaging for lung metastases can be scheduled and access to thoracic surgical expertise facilitated. There is no evidence for benefit in the follow-up of patients with previous breast malignancy, and this follow-up could be done by GPs. However, it is now a requirement for hospitals to produce long-term survival statistics after the treatment of all malignancies, and the only reliable way to collect this data is for patients to be followed up at hospital; this will remain the case until improvements in sharing information technology in the NHS are implemented. For patients with previous breast cancer, a further aspect of follow-up is the detection of new malignancies. Most of these could be detected by mammographic screening alone but, for patients previously treated by conservation surgery, clinical examination, ultrasound and MRI imaging are required to distinguish postoperative fibrosis from recurrence. The recent publication of clinical trial data indicating benefit from ongoing endocrine therapy beyond the standard five years of tamoxifen treatment may also result in patients continuing hospital-based follow-up for a further three years at least. Reconstructive surgery Oncoplastic surgery has become increasingly recognized, particularly in breast surgery. Plastic and reconstructive surgeons have traditionally provided the surgical input for a number of cancer subtypes (e.g. large skin cancers, some cancers of the head and neck, delayed reconstruction after surgery for breast cancer). Most surgical teams have close links with reconstructive surgeons in the specialized field of soft-tissue sarcoma surgery. The major cause of psychological distress in cancer patients is coping with the diagnosis and the possible outcome (see Medical and psychlogical effects of palliative care, page 53). Studies suggest that women who undergo breast conservation have improved body image compared to patients undergoing mastectomy or mastectomy with immediate reconstruction. In terms of overall psychological outcome and social adjustment, there is little evidence of difference between patients treated by mastectomy or mastectomy and reconstruction. However, the altered body image associated with mastectomy and the inconvenience of an external breast prosthesis contribute to psychological distress. A rapid increase in primary reconstructive surgery for patients undergoing mastectomy and wide local excision for breast cancer has been seen recently in many centres.

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The simple option of a subpectoral expanding implant at the time of primary surgery is diminishing, and more sophisticated approaches using latissimus dorsi myocutaneous flaps to cover a prosthesis are becoming more common. This has dramatically reduced the incidence of the major complication of primary reconstruction: infection and extrusion of the implant. The cosmetic results of a latissimus dorsi flap and implant are superior to a simple subpectoral expanding implant. The use of latissimus flaps to reconstruct after wide local excision to permit a larger volume of tissue to be removed is also increasing, as is skin-sparing mastectomy, where a relatively small amount of skin is excised. This oncoplastic approach has disadvantages. The risk of infection is probably greater than a mastectomy without reconstruction, and can take several weeks to resolve. This may have a significant psychological effect and can delay adjuvant therapy. Radiotherapy after primary breast reconstruction may be indicated if, for example, axillary nodes are positive or the tumour is close to the deep margin. Advanced radiotherapy techniques can be utilized, but radiotherapy in the presence of a breast implant is technically challenging and the long-term results are usually disappointing. Reconstruction using abdominal flaps (e.g. TRAM, DIEP flaps) can achieve the most satisfactory cosmetic results, but at a greater risk of flap loss and donor site problems. The overall appearance of the reconstructed breast can be enhanced by nipple reconstruction. The techniques are increasingly within the repertoire of specialist breast surgeons who have appropriate training and expertise in oncoplastic techniques. Role of surgery in palliative care Palliation should be an integral part of all steps in the patient pathway, starting before diagnosis and continuing after death; palliative care involves the care of patients who believe they have malignancy, but are subsequently found not to and, at the other extreme, bereavement support for relatives of terminally ill patients. Most patients with common solid malignancies treated by surgeons will be free of obvious metastases at the time of surgery. Many will subsequently develop metastases and thus their original surgery was palliative. In this sense, one major role of surgery for malignancy is the relief of presenting symptoms and the prevention of distressing symptoms due to the local progression of malignancy. These include ulceration, bleeding, infection and pain in breast cancer and anaemia; obstruction, perforation and peritonitis in gastrointestinal malignancies. Nearly all malignancies cause distressing symptoms due to local progression if not treated adequately and surgeons preoccupation with local recurrence rates is entirely appropriate in this context. For patients to undergo major surgery only to develop early local recurrence is a failure to fulfil the aims of cancer surgery and can result in symptoms that are extremely difficult to palliate (e.g. pelvic recurrence after surgery for rectal cancer). Some solid malignancies are commonly associated with local failure before the development of terminal distant disease, such as pelvic, gastro-oesophageal and pancreatic malignancies. It is in these areas that the role of adjuvant radiotherapy and chemotherapy requires extensive exploration and the technical aspects of surgery; balancing radical excision with acceptable quality of life is crucial. The role of reoperative abdominal surgery for complications due to recurrence of gastrointestinal malignancy within the abdomen
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is a common dilemma for surgeons. Standard investigations often underestimate the extent of recurrence and it is not possible to resect the disease at laparotomy. Occasionally, a localized recurrence may be resectable or a palliative bypass or stoma can be done. Most surgeons believe that the terminal care of intestinal obstruction is difficult and should generally be managed by nonsurgical treatments to reduce gastrointestinal secretions. Orthopaedic surgeons play a major part in the provision of palliative surgery for patients with secondary bone disease, particularly in breast malignancy. Patients presenting with painful metastasis can be treated by localized radiotherapy in addition to analgesia, but patients whose plain radiographs indicate imminent fracture of a long bone (e.g. femur) may benefit from additional prophylactic internal fixation. A substantial group of patients present with a pathological fracture at some stage after their primary treatment; these will not heal by conservative management and internal fixation or arthroplasty improves the care of these patients in terms of symptom relief, mobilization and return home.

Summary
Surgeons are centrally involved in the diagnosis, care and follow-up of patients with a wide number of malignancies. The important skills required in the management of malignancy require further definition and reflection in the training of future surgeons. In this way, surgeons will remain vital to the multidisciplinary approach to cancer management.

CROSS REFERENCES Black J. Is increasing subspecialization going to improve surgical care? Surgery 2003; 21(1): iii. Scholefield J H, Whynes D K. Screening for colorectal cancer in the UK: is it worthwhile? Surgery 2003; 21(7): iiivi.

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2006 Elsevier Ltd