The Changing Role of the Gynaecologist in the Management of Women with Cancer (SAC Opinion Paper 10)

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• The changing Role of the gynaecologist in the management of women with cancer - SAC Opinion Paper 10

1. Introduction

Cancer accounts for 25% of all deaths in the developed world; 40% percent of all surgical procedures are cancer-related and 65% of all cancers occur in people over 65 years of age. Our population is ageing steadily and thus it may seem reasonable to assume, initially at least, that an increasing proportion of surgical resource will be directed toward the management of cancer in the future.

There have been major advances in the science that underpins medical practice and the pace of advance seems almost exponential. It is now timely that the profession re-examines its strategies for dealing with cancer in general and gynaecological cancer in particular. Fundamental to this review is to ask a simple question; ‘Is an anatomically derived intervention such as surgery appropriate for a molecular disorder such as neoplasia?’ The history of medicine is well-illustrated with examples of surgical interventions that have subsequently been phased out in favour of nonsurgical approaches. Without exception, the forces of change have been an improved understanding of pathophysiology and the application of scientifically derived nonsurgical interventions. This process of translating scientific knowledge into improved clinical care is fundamental to medical progress.

It may seem obvious that a traditional surgical approach, no matter how sophisticated, cannot compare with molecular manipulation and nanotechnology, yet there is still some way to go to deliver the scientific promise via robust translational research. Surgery has evolved significantly and has adapted to many of these forces of change. It is the task of this review to speculate on what further changes we might see in the short to medium term, and what the impact of those changes might be.

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2. Gynaecological cancers

Surgery is still relevant as the starting point for diagnosis and treatment of gynaecological cancers. This is reflected in the training given to gynaecological oncologists, which appropriately retains as a major focus achieving surgical competency. If the individual gynaecological oncologist is not to become marginalised then they must be adaptable so that new technologies and ideas can be incorporated speedily into clinical care. To build this adaptability into modern training we must examine closely the factors driving change and establish a sense of direction. Should training, for example, incorporate more interventional radiology, critical care, reconstructive, minimal access and robotic surgery? Should we train gynaecological oncologists to deliver nonsurgical therapies? There are examples in other disciplines, such as vascular surgery, where surgeons are taking on an interventional radiology role after appropriate training. It seems reasonable to suggest that ultrasound skills, particularly guided biopsy and pelvic scanning, should be included in the training curriculum of gynaecological oncologists.

3. What is driving change in gynaecological cancer?

The major forces for changes viewed generically are:

• Knowledge
  Basic science
  Translational science
• Technology
  Surgical instrumentation
  Teleconferencing
  Information technology
  Robotics
• Culture
  Changing patterns of healthcare delivery
  Multidisciplinary and team working
  Commissioning
  Governance and evidence-based practice
  Changing patient demographics (age and obesity)
  Population expectations
  Accessibility of information

Globalisation

When applied specifically to cancer, the following can be identified as important:

• strategies to reduce the burden of disease
• new diagnostic technologies
• new treatments and new ways of delivering old treatments
• strategies to reduce the morbidity of interventions
• multimodality interventions.

A further factor, which will almost certainly impinge on practice, is the way in which cancer services are configured and delivered. This is outside the scope of this review.

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4. Reducing the overall disease burden

There are, of course, general population-based measures which may impact on the overall burden of disease. These include smoking cessation, obesity control and a more focused sexual healthcare policy. More specific measures that relate to gynaecological cancers include vaccination, chemoprevention and screening.

4.1 Vaccination
The goal of prevention of most cervical cancer through vaccination is now a reality. Evidence of human papillomavirus (HPV) infection can be found in virtually all high-grade dysplasias and cancers. Our current understanding of cervical cancer is that it is a rare end-stage event in cervical HPV infection; thus, attempting either to treat the infection via immune modulation or to prevent infection by vaccination seems logical. Such studies have already been performed with encouraging results.^1,2 The impact of vaccination will take many years to become apparent but, at least in the relatively resource-rich developed world, cervical cancer should become even less common. There may also be reductions in vulval and vaginal intraepithelial neoplasias and vulval and vaginal cancers. However, cervical cancer will not be eliminated, as between 20% and 30% of squamous cancers are probably the result of HPV infection that is not the type 16 or 18 cancers to which vaccines are targeted. Vaccination might also impact on the incidence of adenocarcinoma. One meta-analysis has suggested HPV may be involved in up to 82% of adenocarcinomas;³ hence, one might assume a similar impact as is anticipated for the prevention of squamous cancers. One should add that there are no data confirming that vaccination will prevent squamous cancer, only its precursors, and, by inference, the invasive phenotype. The potential impact of vaccination is likely to be greatest in resource-poor nations, where the burden of cervical cancer is highest.

4.2 Chemoprevention
Trials on chemoprevention of breast cancer are well advanced and there may also be scope for applying the same principles to ovarian cancer. The use of combined oral contraceptives significantly reduces the risk of developing ovarian cancer, although paradoxically not to the same extent in those at increased risk through genetic predisposition.⁴ This effect cannot be ascribed to reduced frequency of ovulation, as the reduction is evident even after a relatively short exposure. It may well be an effect on ovarian apoptosis.⁵ Other agents are currently under investigation with a view to cancer prevention in the breast, colon and pancreas. These agents include retinoids and nonsteroidal anti-inflammatory drugs (NSAIDs). In one study the retinoid, fenretinide, appeared to be associated with a significant reduction in the incidence of ovarian cancer, although the effect diminished once the drug was discontinued.⁶ Retinoids and NSAIDs have a positive effect in promoting apoptosis in ovarian cancer cell lines⁷ but, as yet, there are no data from large preventative studies.

Research is focusing on improved evaluation of risk, so that women can receive the optimal chemopreventive agent when diagnosed as being at high risk of cancer. Reducing the overall disease burden in ovarian cancer is a laudable but one suspects it will be a long term goal. A minority of cases of endometrial cancer occur in the premenopausal age group. These cases are seen most frequently in the morbidly obese and in those with polycystic ovary syndrome. These groups might now be considered as high risk for the development of endometrial hyperplasia and neoplasia and consideration should be given to hormonal strategies that could reduce their risk. Progestogen-containing intrauterine contraceptive devices (IUCDs) might realistically be considered partially chemopreventive in this role although as yet there are no data to support them being prophylactic. The POET study (Prevention Of Endometrial Tumours), shortly to be launched, will look at a small group of women who are deemed to be genetically predisposed to develop endometrial cancer at a young age and will evaluate progestogen-containing IUCDs in this setting. One could extend this at-risk category to include obesity in the menopause; successful intervention in this group might result in an even greater impact in the overall incidence of disease than chemotherapeutic agents. While not strictly chemoprevention, the current decline in use of hormone replacement therapy may have an impact on gynaecological cancers, endometrial cancers in particular. Whether this will be offset by the ageing population and increasing obesity remains to be seen.

4.3 Screening
4.3.1 Cervical screening
Cervical screening, appropriately applied and with coverage in excess of 80%, has resulted in a major decline in the incidence of and mortality from cervical cancer.⁸ There has also been some impact on the stage distribution at the time of presentation. The cervical screening programme itself is the subject of change and development through the introduction of new technology. Liquid-based systems are being introduced in the England and Wales and have already been introduced in Scotland, allowing opportunities for automation of the screening process and for investigation and perhaps application of molecular, rather than morphologic, indicators of dysplasia and neoplasia.⁹ Whether this will reduce further the incidence of cervical cancer remains to be seen, although it is likely that the specificity of screening will improve over time. This, combined with the gradual impact of vaccination, will reduce the need for the provision of colposcopy services. Coverage will remain the most important variable in reducing cervical cancer in the population.

4.3.2 Ovarian cancer screening
Ovarian cancer poses a much larger problem in terms of screening. Unlike in cervical cancer, where screening is aimed at detecting an asymptomatic preinvasive phase of the disease, ovarian cancer screening depends on detecting early-stage disease, which has a more favourable outcome. Population screening is being assessed in two settings by controlled trials. The first, UKFOCS (United Kingdom Familial Ovarian Cancer Screening), aims to screen women deemed to be at high risk , while the second, UKTOCS United Kingdom Trial of Ovarian Cancer Screening), is a general population screen. It will be several years before the results of these studies can inform health policy. If these and other studies indicate that ovarian cancer screening is of benefit and viable in terms of health economics, then there could be a shift away from surgery for advanced and somewhat unresectable disease towards treatment for localised disease. The technology employed in ovarian cancer screening includes both ultrasound examination and the tumour marker CA125. Both have limitations but represent the best technology currently available. It is plausible that proteomics and metabolomics combined with enhanced bioinformatics will deliver more precise disease detection and monitoring within the next decade, with parallel developments in enhanced imaging.

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5. Diagnosis and evaluation

The gynaecologist is usually the first point of referral for women who are suspected of having gynaecological cancer. The diagnostic process is therefore directed by the gynaecologist. Surgery is employed in this role to varying degrees, ranging from simple diagnostic or excisional biopsies to ’diagnostic and debulking’ laparotomies with therapeutic intent. Diagnostic laparotomies are usually preceded by a high index of suspicion of malignancy. Similarly, cervical staging procedures are regularly performed to assess both stage and potential operability. The fact that there is ample evidence demonstrating how inaccurate these procedures are¹⁰ does not seem to deter their continued use.

There have been major advances in imaging technology over the last decade. While these techniques are increasingly used, they have, as yet, not become incorporated in formal FIGO staging assessments. This is largely because of access issues, particularly in resource-poor nations. In areas where this technology is available, its impact on practice has been quite obvious. The array of imaging technologies is now quite extensive. In regular use in gynaecological oncology are:

• ultrasonography (sometimes used with Doppler)
• magnetic resonance imaging
• computed tomography
• positron emission tomography
• routine radiology (including contrast studies).

In addition, there is a vigorous research community assessing adaptations of these and new techniques that employ specific marker enhancement (sentinel node scanning) and other biological adjuvants. Combining imaging with directed biopsy and fine-needle aspiration makes them that much more powerful diagnostically. In the near future, it is likely that such techniques will be able both to confirm diagnoses and give a reasonable assessment of the likelihood of complete resectability in ovarian cancer,¹¹ thus avoiding the need for diagnostic laparotomy with the possibility of the residual disease which occurs in over half the cases. It is worth noting that the continuing CHORUS study of delayed surgery in ovarian cancer accepts image-guided biopsy as an entry point to the trial.

Serological markers and high-resolution imaging with guided biopsies have vastly improved our knowledge of tumour status before intervention, adding another dimension to the planning. Highly focused treatment for the individual is now the norm rather than an ethos of ‘one size fits all’. Similarly, we are now more capable of evaluating and preparing patients before intervention. This is essential, given an ageing population with increasing co-morbidity. Many of the skills and disciplines of intensive care and anaesthesiology can now be brought to bear on cases that previously might have been considered unsuitable for any type of intervention other than simple palliation. These skills could, and possibly should now, be included in the training of gynaecological oncologists to further enhance preoperative optimisation.

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6. Interventions

Surgical intervention, both open and endoscopic, will remain an important aspect of gynaecological oncology for the foreseeable future. Competency in pelvic surgery therefore remains of paramount importance and is clearly recognised as such by the RCOG in its favouring a competency-based curriculum. It has been suggested that the surgical skills of gynaecological oncologists in both the USA and mainland Europe are more advanced than their UK counterparts and it seems timely with the adoption of competency-based curriculum that the skill level is revisited and enhanced. It may also be prudent to consider the overall training of gynaecological oncologists with less emphasis on obstetric skill and earlier introduction of surgical training. This will require a wider debate within the obstetrical and gynaecological community but it is an issue that we can no longer afford to ignore.

Intervention in gynaecological oncology may also involve disciplines other than surgery. We are now also much more capable of evaluating and preparing patients before treatment.

6.1 Vulval cancer
Vulval cancer will remain a very uncommon disease. The future management is likely to change radically, as selective lymphadenectomies guided by the sentinel node technique reduce the need for and morbidity from standard inguinofemoral node dissection, a level of morbidity that cannot be understated. There is also likely to be less radical and function-sparing surgery and a greater uptake of reconstructive surgery. The management of these cases are likely to devolve to a small number of highly specialised teams that can offer a full range of interventions yet maintain a workload consistent with skill maintenance and enhancement.

6.2 Cervical cancer
Cervical cancer will become less common in developed countries. There is a clear advantage of chemoradiation over radiation alone at least in smaller volume cancers but morbidity is still of some concern. Surgery is only considered a realistic option in stage Ib and IIa disease, and as an adjunct to palliative strategies, but the range of surgical interventions has increased to allow for fertility-sparing and when possible, ovarian conservation. An increasing number of gynaecological oncologists are questioning the need for radical hysterectomies in small-volume tumours, particularly as the long-term morbidity of this type of surgery becomes more appreciated. Several published series of fertility-sparing surgery suggest that outcomes are as good as radical hysterectomy for small-volume cancers, although there has not as yet been a formal comparison of radical versus non-radical surgical treatment. It is now appreciated that knowledge of nodal status before any planned intervention is likely to result in more appropriate and effective interventions and, in this role, laparoscopy has an obvious application. Whether its use will be superseded by more specific imaging in the future remains to be seen but, for the present, the gynaecological oncologist managing these cancer requires a broader range of skills applied, albeit, to a diminishing population of patients.

6.3 Endometrial cancer
Western population dynamics indicate that there will be an increase in the incidence of endometrial cancer as a function of increasing age and obesity. For early-stage disease it seems likely that a straightforward hysterectomy and bilateral oophorectomy will suffice (PORTEC Trial), with adjuvant radiation given postoperatively for those with known risk factors for pelvic relapse. Neither the PORTEC trial¹² nor the more recent ASTEC trial has suggested a meaningful role for pelvic lymphadenectomy, although sampling of the nodes remains a part of FIGO staging. In high-risk or more advanced disease, the future lies in multimodality care and gynaecological oncologists will play a role in delivering this difficult therapy. The surgical challenges are largely going to be those of operating on the obese and elderly.

6.4 Ovarian cancer
Ovarian cancer is increasingly being regarded as a chronic disease. The majority of women present with advanced disease and most of these will eventually die of disease. Stepwise advancements in therapy over the last 20 years have seen moderate incremental improvements in survival, with more women being offered useful interventions at the time of relapse. In the centres where these women are now treated, it is not unusual to see long-term survivors who may have had two or more successful courses of chemotherapy. We are also just beginning to see the fruits of extensive laboratory research as they translate into clinical care, specifically with targeted therapies. These agents will offer an increased scope and breadth of management options for this challenging disease, adding to that which has already been achieved.

This concept, of a relentless yet manageable disease, is new in gynaecological oncology and requires a re-evaluation of treatment endpoints and long-term treatment strategies. Relapse and symptom-free survival are perhaps the more important endpoints when considering the outcome of intervention therapies during the course of a chronic disease. To date, most attention has been focused on the role of initial disease cytoreduction (primary laparotomy) and of medical interventions, including conventional chemotherapeutic agents and, latterly, biological agents. Surgery may also have a role in prolonging life and maintaining a good quality of life. The older literature contains references to so-called secondary cytoreduction surgery where it has been possible in selected cases to demonstrate enhanced and prolonged survival following re-resection of disease. Before the inception of cancer centres and networks, most of these women were managed by a variety of gynaecologists, many of whom lacked the training or skills to undertake more complex reoperation that is implicit in this type of approach to recurrent disease. Ovarian cancer, above all, demonstrates the need for multidisciplinary working and the extensive range of surgical competencies required to achieve maximal resection with least morbidity.

6.5 Palliative care
Approximately 50% of the women who present with a newly diagnosed gynaecological cancer will eventually die as a direct result of their disease. These figures are an approximate and will vary geographically as a result of case mix and stage at presentation. Nevertheless, it is salutary to consider that palliative effort receives disproportionately less time and study than does our continued effort to ‘cure’ patients with gynaecological cancer.

Surgical intervention is not normally regarded as a front-line palliative approach. However, there are well-recognised areas within gynaecological oncology where this type of intervention has a major role. These include:

• alleviation of symptoms of gastrointestinal tract obstruction where medical interventions are either inappropriate or ineffective
• removal of cutaneous lesions and recurrence in wounds and port sites
• bypass of either bowel or urinary tract, or both, if they are causing severe fistula-related symptoms
• removal of a localised intra-abdominal mass causing symptoms.

As with other forms of palliative intervention, the principle is to do that which has least morbidity and will effect greatest symptom relief.

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7. Summary

In the short to medium term, there is unlikely to be a major reduction in the overall caseload that is referred into gynaecological cancer centres. There will continue to be a gradual decrease in the numbers of cervical cancer and further reductions might depend upon the impact of vaccination. This, however, is likely to be offset by an increase in endometrial cancer and possible smaller increases in ovarian and vulval cancer as the population ages. An increasing appreciation of genetic predisposition will also contribute to the surgical workload by identifying women who may benefit from risk-reducing surgery, although the numbers are likely to be small.

Non-surgical intervention and improved diagnostic technology might bring about reductions in the actual number of women requiring some form of surgery, yet the variety of surgical interventions and the necessary expertise to deliver them safely will increase. Surgical and medical competence must therefore remain high on the training agenda. A further variable that will need to be factored into the training and manpower debate is the possible change in overall surgical competence in those who adopt a ‘nononcological’ career stream. If gynaecological oncologists are going to be required to take on the complex but benign work that hitherto has been undertaken by those who have received a more traditional training, then manpower calculations and training requirements need to be adjusted accordingly.

Finally, the trained gynaecological oncologist should not be regarded as a ‘finished product’. From the above observations, it will be apparent that all clinicians in the future need to be allocated the time and resource to incorporate new technologies and competencies into their routine clinical roles. For this to occur, more than ‘lip service’ has to be paid to effective in-service training, with a more liberal approach to sabbatical training and exchanges. This will also impact on the overall manpower needs of an effective and modern service.

References

1. Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, et al. GlaxoSmithKline HPV Vaccine Study Group. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004;364(9447):1757–65.
2. Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus–like particle vaccine in young women: a randomised double-blind placebocontrolled multicentre phase II efficacy trial. Lancet Oncol 2005;6(5):271–8
3. Castellsague X, Diaz M, de Sanjose S, Munoz N, Herrero R, Franceschi S, et al; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst. 2006;98(5):303–15
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6. De Palo G, Mariani L, Camerini T, Marubini E, Formelli F, Pasini B, et al. Effect of fenretinide on ovarian carcinoma occurrence. Gynecol Oncol 2002;;86(1):24–7.
7. Rodriguez-Burford C, Barnes MN, Oelschlager DK, Myers RB, Talley LI, Partridge EE, et al. Effects of nonsteroidal anti-inflammatory agents (NSAIDs) on ovarian carcinoma cell lines: preclinical evaluation of NSAIDs as chemopreventive agents. Clin Cancer Res 2002;8(1):202–9.
8. Baker D, Middleton E. Cervical screening and health inequality in England in the 1990s. J Epidemiol Community Health. 2003;57(6):417–23.
9. Dallenbach-Hellweg G, Trunk MJ, von Knebel Doeberitz M. Traditional and new molecular methods for early detection of cervical cancer. Arkh Patol. 2004;66(5):35–9
10. Nguyen HN, Averette HE. Biology of cervical carcinoma. Semin Surg Oncol 1999;16(3):212–6.
11. Byrom J, Widjaja E, Redman CW, Jones PW, Tebby S. Can pre-operative computed tomography predict resectability of ovarian cancer at primary laparotomy? BJOG 2003;110(8):369–75.
12. Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ; PORTEC Study Group. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet 2000;355(9213):1404–11.

This opinion paper was produced on behalf of the Royal College of Obstetricians and Gynaecologists by:
Professor DM Luesley FRCOG
and peer reviewed by:
Dr LJ Cassidy FRCOG, Greenock, Scotland; Mr RAF Crawford FRCOG, Cambridge; Dr JA Davis FRCOG, Glasgow, Scotland; Dr ID Duncan FRCOG, Dundee, Scotland; Professor WP Soutter FRCOG, London

The final version is the responsibility of the Scientific Advisory Committee of the RCOG.

The review process will commence in November 2010 unless otherwise indicated

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