Indian Journal of Surgery Medknow Publications on behalf of Association of Surgeons of India ISSN: 0972-2068 Vol. 65, Num. 4, 2003, pp. 317-319

Indian Journal of Surgery, Vol. 65, No. 4, July-Aug, 2003, pp. 317-319

Editorial

The shifting paradigm in Oncology - Redefining the Surgeon's role

Praful B. Desai

Department of Oncosurgery, Bombay Hospital Institute of Medical Sciences, Marine Lines, Mumbai 400020.
Address for correspondence Dr. Praful B. Desai, 307, Samudra Mahal, Dr. A. B. Road, Worli, Mumbai 400036. E-mail: praful@bol.net.in

Paper Received: January 2003. Paper Accepted: January 2003. Source of Support: Nil

Code Number: is03064

The practice of medicine has witnessed a sea change in the last decade. A clinically oriented science has rapidly changed into a technology-oriented profession. Change is necessary with passage of time and change we must for the benefit of our patientsnot only to control or cure their disease but more importantly to address quality of life issues which often come to the fore when technology dictates management in a given clinical setting.

Apart from the exciting technological innovations of the last two decades, our increased understanding of the biology of the human system in health and disease has made major impacts on surgical sciences and the way we now need to practise surgery. Nowhere have these factors made a greater impact than in the practice of Surgical Oncology. Let me hasten to add that though we need to modify our surgical approaches to cancer, the age-old surgical principles have NOT changed; indeed, they have been reinforced more than ever before.

This special issue of Indian Journal of Surgery addresses the issue of conservation surgery for malignant diseases. Surgery has been the oldest method of cancer treatment and even today continues to be the major therapeutic approach to solid tumours in most parts of the body, be it be the brain, the head and neck, upper aero-digestive or respiratory organs, the gastrointestinal tract, bone, soft tissues, breast or the genito-urinary system. Surgical principle enunciated more than a century ago about "removing the growth, the growth as a whole and the growing ends of the growth" literally means to adequate removal of the primary tumour with a wide free margin and adequate removal of infiltrated lymph nodes. All the progress in chemotherapy and radiotherapy has NOT altered this surgical principle no matter which tumour we are dealing with. Too often, as happened in wound infections and antimicrobial therapy, the surgeon became a bit complacent in conforming to surgical principles under the umbrella of radiotherapy and chemotherapy to the detriment of the patients' interest. Just as infections increased despite antibiotics, local recurrences after primary surgery increased despite chemotherapy and radiotherapy, entirely due to the neglect of surgical principles while dealing with malignant disease.

Conservation surgery should not sacrifice surgical principles. However, our biological understanding, sophistication in radiotherapy and more efficient chemotherapy drugs now allow us to shy away from mutilating surgery of the past like mastectomies, amputations, extensive lymph node dissections (neck, axilla, groin), radical surgeries in the head and neck region like laryngectomies, and composite commando type of operations. Preservation of the breast, bladder, the prostate, the rectum, and the anal sphincters is now more frequently possible as the strengths and weaknesses of surgery, radiotherapy and chemotherapy are complemented to achieve the overall objective of prolonged control or cure with a good quality of life. Needless to state that when indicated, resorting to the earlier conventional procedures does become necessary if patients present late. Public education is therefore extremely important for early diagnosis and effective conservation surgery. This requires much greater experience as a surgical oncologist. Today there is enough published evidence and documentation to state that conservation surgery in oncology, when indicated, leads to the same end results and hence has become a standard of care.¹ Unnecessary radical procedures cannot stand scientific scrutiny and need to be questioned. Much morbidity can be avoided and quality of life is infinitely superior with appropriate conservation surgery.

The role of palliative resections

Of all the surgical resections performed with intent to cure (for localized disease) only 40% will result in an R₀ resection (complete macroscopic surgical clearance). In more than 60% cases, surgical resections will leave behind either microscopic disease (R₁ Resection) or gross unresectable tumour infiltrations due to proximity to vital structures (R₂ Resection). Current imaging techniques should increase R₀ resections to around 70 %. Despite this scenario, safe surgical resection is still the best form of palliation as it rids the patient of the primary lesion which is the source of metastasis, pain, bleeding, obstruction and other distressing symptoms.

It is imperative, therefore, for the surgical oncologist to know the nuances of adjuvant postoperative therapy (chemotherapy or radiotherapy)-depending on the biology and natural history of the primary disease. Even more importantly, it is necessary to predict the need of neo-adjuvant chemo/radiotherapy before definitive surgical procedure when the primary tumour and nodal burden is too large for a clean and safe surgical resection. Mapping out the total profile of the disease by routine investigations and imaging techniques like the CT, MRI, EUS, and systemic scans (when indicated), is therefore crucial for the most appropriate initial therapy in a given clinical setting. The TOTAL profile of a disease should dictate the initial therapy approach.

It is now standard care to treat solid tumours (breast, head and neck, oesophagus, gastrointestinal tract, bone and soft tissues, genito-urinary tract, etc.) by appropriate neo-adjuvant chemotherapy (prior to surgical intervention) when the local primary tumour is advanced and/or has metastasized. This not only reduces the primary lesion but may even allow organ conservation by appropriate local radiotherapy (breast, larynx, pharynx, oesophagus, etc.). These nuances of appropriate interpolation of surgery, radiotherapy and chemotherapy need to be understood by a general surgeon to be able to offer a state-of-the-art therapy to the patient and improve quality of life.

Surgical debulking and metastatectomy

Many techniques are now available for cytoreductive procedures. The principle is to debulk so that the residuum can be more efficiently dealt with by chemotherapy or radiotherapy. Foremost among cytoreductive techniques are palliative surgical resections just alluded to, cryoablation, radio frequency ablation, ethanol injections, embolization, laserization and photodynamic therapies. Each has its own indication and will provide a varying degree of palliation depending on the primary tumour, its natural history and biological characteristics.

Classical examples in surgical oncology for debulking are ovarian and testicular cancers after neo-adjuvant chemotherapy. Palliative liver, lung and pancreatic resections for neuro-endocrine tumours (carcinoids) often lead to prolonged palliation and occasional cures with a much improved quality of life.² The surgical oncologist needs to be conversant with the natural history of a given tumour and should be capable of accomplishing complex surgical procedures with dexterity and safety.

Long-term palliation and some cures are also documented by performing metastatectomy (of liver, lung, brain and abdominal metastasis) arising from a primary cancer of the kidney, GI tract, bone and soft tissue sarcomas.³ Once again nuances of biological behaviour have to be respected. Long-term control of the primary cancer, resectable solitary metastasis (or occasionally multiple) are prerequisites of a successful outcome after metastatectomy. 25 to 30% survivals at 5 yrs are documented after appropriate patient selection.⁴

Even a major right lobe hepatectomy from a colonic cancer is known to afford good palliation. Indeed, there is no place for a reluctant surgical oncologist who is not ready to be surgically aggressive when necessary and indicated.

Biological approaches to cancer: the impact of molecular biology

Though conventionally surgery has been the oldest method of cancer treatment and even today remains the mainstay of the management of most cancers, it is important to realize that surgery and radiotherapy are essentially local methods of treatment and too often surgeons have failed and lost the battle against cancer at a metastatic site. Chemotherapy came upon the scene by 1960 and four decades later has helped the surgeon and the radiotherapist in a very significant manner to improve the results in cancer treatment.

Though we gained some ground, the complementary efforts of the surgeon, radiotherapist and chemotherapist failed to show a quantum leap in cure rates; in fact, the results of cancer treatment reached a plateau by the 1980s and the 1990s.

The current era of biological revolution is slowly and steadily unraveling the fundamentals of the molecular biology of normal and cancer cells. Chemotherapy targets the cell cycle phase when the cell is dividing most actively (proliferative phase) by targeting the DNA, the RNA and protein synthesis. The drugs are generally tumour-selective only if the tumour cells proliferate faster than normal cells, which is not always the case.

Current knowledge in molecular biology has proved the great importance of apoptosis (programmed cell death), tumour angiogenesis, vascular endothelial growth factor vascular endothelial growth factor (VEGF), signal transduction and invasion among other biological processes in the cell to be mainly responsible for cancer transformation and progression. These could be our molecular targets to block carcinogenesis and subsequent metastasis. We now have, albeit in very preliminary studies, biological agents which can block these biological processes and prevent cancer. Thus a combination of molecular target inhibitors (biological agents) and standard chemotherapy drugs may provide real tumour selectivity.

For example, tumour angiogenesis (the formation of new blood vessels) is necessary for tumour growth beyond 2 mm in diameter as well as for invasion and metastasis.⁵ Whereas hypoxia (in a rapidly growing tumour) triggers angiogenesis by generating a series of angiogenic factors including VEGF,⁶ in many tumors angiogenesis is induced by genetic alterations. Like VEGF, oncogene pathways may be targets for anti-angiogenesis cancer therapy. VEGF is currently targeted in cancer patients, in clinical trials using VEGF antibodies.

This scenario in cancer research today may bring such biological agents as an important component in cancer treatment along with surgery, radiotherapy and chemotherapy. It is necessary to state however, that the much promised biological therapy of the 80s and 90s like interferons, interleukins, and monoclonal antibodies have not made any significant headway in improving our overall results. Basic research and its therapeutic impact is a very slow and halting process and it is unrealistic for us or the public to expect quantum leaps towards cancer cure.

REFERENCES

1. Fisher B, Anderson S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. Reanalysis & results after 12 years of following in a randomised clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Eng J Med 1995;333:1456-61.
2. Nave H, Missinga E, Fiest H, Lang H, Raab H. Surgery as primary treatment in patients with liver metastases from tumors: a retrospective unicentric study over 13 years. Surgery 2001;129: 170-5.
3. Melormack PM, Burt ME, Bains MS, Martini N, Rusch VW, Ginsberg RJ. Lung resection for colorectal metastases: 10-year results. Arch Surg 1992;127:1403-6.
4. Dennis L, Rousseau Jr, Gregory P Thidis. Cancer or the colon rectum and anus. In: Anderson MD, editor. Surg Oncology Handbook. 3rd edn. pp. 251.
5. Folkman J. Tumor angiogenesis: therapeutic implications. N Eng J Med 1971;285:1182-6.
6. Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992;359:843-5.

© 2003 Indian Journal of Surgery. Also available online at http://www.indianjsurg.com