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How should we introduce clinical positron emission tomography in the UK? Oncologists need to have a (clearer) view
Clinical Oncology (2004) 16: 492–493 doi:10.1016/j.clon.2004.08.001
Editorial How Should We Introduce Clinical Positron Emission Tomography in the UK? Oncologists Need to Have a (clearer) View M. Mac Manus*, L. Peters*, G. Duchesne*, J. Zalcbergy, R. J. S. Thomasz, D. Ballx, R. Hicksk *Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia; yDivision of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia; zDivision of Surgical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia; xLung Unit, Peter MacCallum Cancer Centre, East Melbourne, Australia; kCentre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne, Australia
Introduction
It was with great interest that we read the recent editorial by Price and Laking on clinical positron emission tomography (PET) [1]. Although the article was clearly targeted at clinical oncologists in the UK, we believe that the issues raised are internationally relevant. Therefore, we wish to comment from our perspective as clinicians who work at a large cancer centre that contains the first Australian PET facility primarily dedicated to clinical service provision [2]. Over 15 000 scans in around 10 000 patients have been carried out in our institute. Selective use of PET is now integral to our daily clinical practice because of the major impact it has on treatment decisions. The Strength of the Evidence for PET
Although the great clinical utility of PET is immediately apparent to any oncologist with practical daily experience of its use, our enthusiasm for PET is also based on an active clinical research programme with prolonged follow-up of our patient population [3]. Furthermore, as Price and Laking acknowledge, there is substantial evidence that clinical PET, using fluorodeoxyglucose (FDG), can improve the diagnostic staging of cancer. More than 10 years of publications have demonstrated the superiority of PET over conventional staging techniques. This literature is strikingly consistent. In Author for correspondence: M. Mac Manus, Associate Professor, Peter MacCallum Cancer Centre, Department of Radiation Oncology, St Andrews Place, East Melbourne, Vic 3002, Australia. Tel: C61-3-9656-1111; Fax: C61-3-9656-1424.; E-mail: [email protected] 0936-6555/04/070492C02 $35.00/0
addition, the demonstration that PET robustly stratifies patient survival in many oncological settings is a compelling demonstration of the clinical efficacy of PET as a staging investigation. As clinicians, we regard this evidence of superior staging accuracy as unequivocal evidence of patient benefit, because there are many paradigms in which the current standard of care is solely dependent upon accurate staging. For example, we believe it is impossible to argue that avoiding surgery or radiotherapy in a patient in whom PET correctly determines does not have disease (as confirmed by prolonged remission without active intervention) is not a positive outcome; nor can it be argued that sparing a patient the morbidity of a futile attempt at surgical or radiotherapeutic cure when metastases are correctly identified by PET (as confirmed by progression of disease at these sites) is not worthwhile for both the patient and the community independent of any survival benefit, which might or might not accrue from these changes in management. In addition, increasing evidence has shown that PET significantly and appropriately changes therapeutic decisions in a substantial proportion of people with common malignancies. Unlike Price and Laking, we are not deterred by the lack of multiple large randomised trials looking at patient survival, because it is clear that the ability of PET to influence survival is primarily dependent upon the efficacy and toxicity of competing treatment strategies. Indeed, published evidence shows that patients selected for radical radiotherapy with the aid of PET can achieve much better survival than conventionally staged patients [4], suggesting that existing treatments may be more effective than is generally appreciated, if only patient selection were more appropriate.
Ó 2004 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
CLINICAL PET IN THE UK
Therefore, we strongly disagree that the evidence supporting PET is insufficient to conclude that PET truly benefits patients. We believe that restriction of PET to a limited number of well-funded institutions to carry out more research, when the evidence is already compelling, is waste of resources, may be unethical and will unnecessarily delay the wider availability of an invaluable oncological investigation. It should not be forgotten that evidence hierarchies, such as the one popularised by Fryback and Thornbury [5], are designed to assess societal benefit and are not directly applicable to clinical management decisions. Few of our patients consult us with the benefit of the society at large as their primary concern. Indeed, most patients with cancer want us to give them information and treatment that will allow them to maximise the quantity and quality of their own lives! The Cost of Positron Emission Tomography
One of the major issues considered in producing Health Technology Assessment reviews, and echoed in the editorial opinion, is the perception that PET is a highcost investigation. It is true that PET has been a relatively expensive modality, but economies of scale are already favourably affecting instrumentation and radiopharmaceutical costs. We have seen a significant relative reduction in cost, compared with features delivered, for computed tomography and magnetic resonance imaging, and there is no reason to suggest that this cannot or will not happen for PET as the installed base increases. In our own facility, despite introduction of more complex and expensive PET/computed tomography technology, the unit cost for PET studies has not increased significantly because of much higher throughput and more efficient use of resources. Even without addressing the costs of PET, it needs to be recognised that the major costs of modern oncology practice lie not in the diagnostic process but in the delivery of treatment, such as the costs of aggressive treatments that are used inappropriately in patients with advanced disease, which could have been detected by PET; the direct and indirect morbidity-related costs of ineffective therapies, which could be identified as such by the superior therapeutic monitoring capabilities of PET; and the costs of delayed detection of recurrence at a suitable time to salvage patients with PET-detectable locoregional relapse could potentially completely offset the costs of PET. Consistent with this, various decisiontree analyses have suggested that PET might be cost-effective, compared with current bench-marks, and potentially cost saving [6,7]. The Model of Clinical Positron Emission Tomography Practice
One of the major dilemmas in how to structure and fund PET services relates to various models of PET practice.
493
Traditionally, PET has been used primarily as a research modality, with a low number of scans and a high staffto-scan ratio. This model has provided unique insights into the mechanisms of various diseases [8], but leads inevitably to inefficient use of expensive equipment. On the other hand, a combination of high throughput clinical facilities with staffing levels that are appropriate to clinical service requirements with economies of scale and a competitive FDG production market, would significantly reduce the per scan cost of PET. It is pertinent to note that the expansion of PET throughout the world has been based on the second model. The Way Forward
Although we share the enthusiasm of Price and Laking for the research potential of PET, we believe that entrenching the inefficient models of PET practice and research methodologies that have proliferated in ‘academic PET’ centres throughout the world must be resisted. A ‘too little, too late’ implementation of clinical PET will not only impair the UK’s reputation as a provider of high-quality cancer care, but will also lead to continuing disadvantage to individual patients who are denied access to this technology. FDG PET already provides oncologists with a clearer means for selecting patients for aggressive therapies, assistance with targeting treatments, such as radiotherapy, and it can provide information on the effectiveness of treatment after it has been delivered. We believe that oncologists should act first as advocates for quality health care for their patients rather than as gatekeepers of the public purse. We acknowledge the need for financial prudence, but let us have consistency of application of economic benchmarks to all aspects of health expenditure and indeed to other areas of government expenditure.
References 1 Price P, Laking G. How should we introduce clinical PET in the UK? The oncologists need to have a view. Clin Oncol 2004;16:172–175. 2 Hicks RJ, Binns DS, Fawcett ME, et al. Positron emission tomography (PET): experience with a large-field-of-view three-dimensional PET scanner. Med J Aust 1999;171:529–532. 3 Hicks RJ, Mac Manus MP. 18F-FDG PET in candidates for radiation therapy: is it important and how do we validate its impact? J Nucl Med 2003;44:30–32. 4 MacManus MP, Wong K, Hicks RJ, et al. Early mortality following radical radiotherapy (RRT) for non-small cell lung cancer (NSCLC): comparison of PET-staged and conventionally-staged cohorts treated at a large tertiary-referral center. Int J Radiat Oncol Biol Phys 2002;52: 351–361. 5 Thornbury JR, Fryback DG. Technology assessment: an American view. Eur J Radiol 1992;14:147–156. 6 Valk PE, Pounds TR, Tesar RD, et al. Cost-effectiveness of PET imaging in clinical oncology. Nucl Med Biol 1996;23:737–743. 7 Miles KA. An approach to demonstrating cost-effectiveness of diagnostic imaging modalities in Australia illustrated by positron emission tomography. Australas Radiol 2001;45:9–18. 8 Phelps ME. PET: the merging of biology and imaging into molecular imaging. J Nucl Med 2000;41:661–681.
Editorial How Should We Introduce Clinical Positron Emission Tomography in the UK? Oncologists Need to Have a (clearer) View M. Mac Manus*, L. Peters*, G. Duchesne*, J. Zalcbergy, R. J. S. Thomasz, D. Ballx, R. Hicksk *Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia; yDivision of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia; zDivision of Surgical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia; xLung Unit, Peter MacCallum Cancer Centre, East Melbourne, Australia; kCentre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne, Australia
Introduction
It was with great interest that we read the recent editorial by Price and Laking on clinical positron emission tomography (PET) [1]. Although the article was clearly targeted at clinical oncologists in the UK, we believe that the issues raised are internationally relevant. Therefore, we wish to comment from our perspective as clinicians who work at a large cancer centre that contains the first Australian PET facility primarily dedicated to clinical service provision [2]. Over 15 000 scans in around 10 000 patients have been carried out in our institute. Selective use of PET is now integral to our daily clinical practice because of the major impact it has on treatment decisions. The Strength of the Evidence for PET
Although the great clinical utility of PET is immediately apparent to any oncologist with practical daily experience of its use, our enthusiasm for PET is also based on an active clinical research programme with prolonged follow-up of our patient population [3]. Furthermore, as Price and Laking acknowledge, there is substantial evidence that clinical PET, using fluorodeoxyglucose (FDG), can improve the diagnostic staging of cancer. More than 10 years of publications have demonstrated the superiority of PET over conventional staging techniques. This literature is strikingly consistent. In Author for correspondence: M. Mac Manus, Associate Professor, Peter MacCallum Cancer Centre, Department of Radiation Oncology, St Andrews Place, East Melbourne, Vic 3002, Australia. Tel: C61-3-9656-1111; Fax: C61-3-9656-1424.; E-mail: [email protected] 0936-6555/04/070492C02 $35.00/0
addition, the demonstration that PET robustly stratifies patient survival in many oncological settings is a compelling demonstration of the clinical efficacy of PET as a staging investigation. As clinicians, we regard this evidence of superior staging accuracy as unequivocal evidence of patient benefit, because there are many paradigms in which the current standard of care is solely dependent upon accurate staging. For example, we believe it is impossible to argue that avoiding surgery or radiotherapy in a patient in whom PET correctly determines does not have disease (as confirmed by prolonged remission without active intervention) is not a positive outcome; nor can it be argued that sparing a patient the morbidity of a futile attempt at surgical or radiotherapeutic cure when metastases are correctly identified by PET (as confirmed by progression of disease at these sites) is not worthwhile for both the patient and the community independent of any survival benefit, which might or might not accrue from these changes in management. In addition, increasing evidence has shown that PET significantly and appropriately changes therapeutic decisions in a substantial proportion of people with common malignancies. Unlike Price and Laking, we are not deterred by the lack of multiple large randomised trials looking at patient survival, because it is clear that the ability of PET to influence survival is primarily dependent upon the efficacy and toxicity of competing treatment strategies. Indeed, published evidence shows that patients selected for radical radiotherapy with the aid of PET can achieve much better survival than conventionally staged patients [4], suggesting that existing treatments may be more effective than is generally appreciated, if only patient selection were more appropriate.
Ó 2004 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
CLINICAL PET IN THE UK
Therefore, we strongly disagree that the evidence supporting PET is insufficient to conclude that PET truly benefits patients. We believe that restriction of PET to a limited number of well-funded institutions to carry out more research, when the evidence is already compelling, is waste of resources, may be unethical and will unnecessarily delay the wider availability of an invaluable oncological investigation. It should not be forgotten that evidence hierarchies, such as the one popularised by Fryback and Thornbury [5], are designed to assess societal benefit and are not directly applicable to clinical management decisions. Few of our patients consult us with the benefit of the society at large as their primary concern. Indeed, most patients with cancer want us to give them information and treatment that will allow them to maximise the quantity and quality of their own lives! The Cost of Positron Emission Tomography
One of the major issues considered in producing Health Technology Assessment reviews, and echoed in the editorial opinion, is the perception that PET is a highcost investigation. It is true that PET has been a relatively expensive modality, but economies of scale are already favourably affecting instrumentation and radiopharmaceutical costs. We have seen a significant relative reduction in cost, compared with features delivered, for computed tomography and magnetic resonance imaging, and there is no reason to suggest that this cannot or will not happen for PET as the installed base increases. In our own facility, despite introduction of more complex and expensive PET/computed tomography technology, the unit cost for PET studies has not increased significantly because of much higher throughput and more efficient use of resources. Even without addressing the costs of PET, it needs to be recognised that the major costs of modern oncology practice lie not in the diagnostic process but in the delivery of treatment, such as the costs of aggressive treatments that are used inappropriately in patients with advanced disease, which could have been detected by PET; the direct and indirect morbidity-related costs of ineffective therapies, which could be identified as such by the superior therapeutic monitoring capabilities of PET; and the costs of delayed detection of recurrence at a suitable time to salvage patients with PET-detectable locoregional relapse could potentially completely offset the costs of PET. Consistent with this, various decisiontree analyses have suggested that PET might be cost-effective, compared with current bench-marks, and potentially cost saving [6,7]. The Model of Clinical Positron Emission Tomography Practice
One of the major dilemmas in how to structure and fund PET services relates to various models of PET practice.
493
Traditionally, PET has been used primarily as a research modality, with a low number of scans and a high staffto-scan ratio. This model has provided unique insights into the mechanisms of various diseases [8], but leads inevitably to inefficient use of expensive equipment. On the other hand, a combination of high throughput clinical facilities with staffing levels that are appropriate to clinical service requirements with economies of scale and a competitive FDG production market, would significantly reduce the per scan cost of PET. It is pertinent to note that the expansion of PET throughout the world has been based on the second model. The Way Forward
Although we share the enthusiasm of Price and Laking for the research potential of PET, we believe that entrenching the inefficient models of PET practice and research methodologies that have proliferated in ‘academic PET’ centres throughout the world must be resisted. A ‘too little, too late’ implementation of clinical PET will not only impair the UK’s reputation as a provider of high-quality cancer care, but will also lead to continuing disadvantage to individual patients who are denied access to this technology. FDG PET already provides oncologists with a clearer means for selecting patients for aggressive therapies, assistance with targeting treatments, such as radiotherapy, and it can provide information on the effectiveness of treatment after it has been delivered. We believe that oncologists should act first as advocates for quality health care for their patients rather than as gatekeepers of the public purse. We acknowledge the need for financial prudence, but let us have consistency of application of economic benchmarks to all aspects of health expenditure and indeed to other areas of government expenditure.
References 1 Price P, Laking G. How should we introduce clinical PET in the UK? The oncologists need to have a view. Clin Oncol 2004;16:172–175. 2 Hicks RJ, Binns DS, Fawcett ME, et al. Positron emission tomography (PET): experience with a large-field-of-view three-dimensional PET scanner. Med J Aust 1999;171:529–532. 3 Hicks RJ, Mac Manus MP. 18F-FDG PET in candidates for radiation therapy: is it important and how do we validate its impact? J Nucl Med 2003;44:30–32. 4 MacManus MP, Wong K, Hicks RJ, et al. Early mortality following radical radiotherapy (RRT) for non-small cell lung cancer (NSCLC): comparison of PET-staged and conventionally-staged cohorts treated at a large tertiary-referral center. Int J Radiat Oncol Biol Phys 2002;52: 351–361. 5 Thornbury JR, Fryback DG. Technology assessment: an American view. Eur J Radiol 1992;14:147–156. 6 Valk PE, Pounds TR, Tesar RD, et al. Cost-effectiveness of PET imaging in clinical oncology. Nucl Med Biol 1996;23:737–743. 7 Miles KA. An approach to demonstrating cost-effectiveness of diagnostic imaging modalities in Australia illustrated by positron emission tomography. Australas Radiol 2001;45:9–18. 8 Phelps ME. PET: the merging of biology and imaging into molecular imaging. J Nucl Med 2000;41:661–681.