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Active surveillance for genitourinary cancer: An overview
Urologic Oncology: Seminars and Original Investigations 24 (2006) 44 – 45
Seminar section introduction
Active surveillance for genitourinary cancer: An overview Look There he is now, look: There is no interrogation in his eyes Or in the hands, quiet over the horse’s neck, And the eyes watchful, waiting, perceiving indifferent. O hidden under the dover’s wing, hidden in the turtle’s breast . . . —T.S. Elliot 20th Century approach to cancer: Seek and Destroy 21st Century approach to cancer: Target and Control —A. von Eschenbach, Director, NCI
Site by site in genitourinary oncology, a management strategy of surveillance with selective intervention for progression has become established as a valid treatment option. The surveillance approach is usually adopted because of evidence in a site that treatment is not substantially altering the natural history of disease in some patients. In urologic cancer, this concept is more prevalent at the favorable end of the spectrum, where earlier diagnosis, improved imaging, and more aggressive biopsy strategies have resulted in the detection of many nonlife-threatening cancers. There is a range of scenarios in uro-oncology in which skepticism about the value of routine intervention is warranted. These scenarios include: clinical stage 1 testicular cancer, in which retroperitoneal lymph node dissection has a 70% chance of being pathologically negative; indolent prostate cancer, which is not destined to progress during the patient’s lifetime; the Papillary Urothelial Neoplasm of Low Malignant Potential, which carries essentially no risk of metastasis or progression; and the small, incidentally discovered renal mass in an elderly patient. The surveillance approach, with selective delayed intervention for evidence of progression, has the potential to be a cancer treatment strategy for a wide range of malignancies. The concept is consistent the Dr. Von Eschenbach’s view, previously mentioned, that the future of cancer treatment will involve a more nuanced and personalized approach, using molecular, biochemical, and imaging parameters to individualize therapy. The analogy of barnyard animals in a pen is relevant. Life in the barnyard represents local disease; escape outside the fence equates to metastasis. The turtles, which remain in the yard, are optimally treated with surveillance; they will remain stable and show no tendency to metastases. The 1078-1439/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved.
birds fly away early and are also reasonably treated with initial surveillance. For patients with highly metastatic lesions that spread shortly after inception, aggressive local therapy is not likely to alter the outcome. (These patients will receive palliative therapy upon progression.) The rabbits, which hop around inside the yard for a while before jumping out, are the only ones who benefit from early detection and treatment. The limitation is that differentiating accurately between rabbits and turtles in cancer may not be easy. The close surveillance of favorable risk disease to enhance this distinction is a compelling concept. This means incorporating natural history into the decision algorithm, with selective delayed intervention for the subset with rabbit-like features. To extend the analogy, the concept is to tailor surveillance for each turtle-like cancer so that as soon as it is found to have a furry white tail, definitive therapy is implemented. Active surveillance as a model for cancer treatment is only appropriate when certain cancer and treatment characteristics are present. These characteristics include the ability to identify patients who are likely to have indolent cancer or benign disease, in a disease in which slow growth is common. There must be a method to identify patients with progressive disease. There must be significant adverse effects of treatment and evidence that delayed treatment is still effective for those who need it. Surveillance may also be reasonable based on patient characteristics, even if these criteria are not fulfilled. Patients with a limited life expectancy based on age and/or comorbidity, relative to the usual natural history of that patient’s cancer, are obvious candidates. These criteria are met to various degrees in prostate, testis, renal, and bladder cancer. In this series, the case for active surveillance with selective delayed intervention is made for each of these cancers. In prostate cancer, the problem of over-treatment of indolent disease is incontrovertible, and the case for surveillance of patients with favorable risk disease is compelling. In this series, we have included 2 perspectives on active surveillance: the “Hopkins” view, which is strongly supportive of the concept in very carefully select patients; and the “Toronto” view, which takes a more “aggressive” stance toward surveillance in terms of considering a larger proportion of patients to be appropriate candidates. In testis cancer, the disease is rap-
L. Klotz / Urologic Oncology: Seminars and Original Investigations 24 (2006) 44 – 45
idly growing and life threatening, but the opportunity provided by effective salvage therapy for patients who have recurrence enhances the appeal of an initial surveillance approach. The case for surveillance for both seminoma and nonseminoma is made in 2 separate, definitive articles. The article on renal cancer surveillance describes the marked stage migration that has occurred as a result of the routine use of abdominal imaging. This has resulted in many cases being diagnosed that would not have been identified before death in a previous era. Recent data suggest that like prostate cancer, many small renal tumors behave in a very indolent fashion and may not require treatment; the ones that progress are still amenable to cure. In addition, a significant proportion proves to be benign, further strengthening the value of an initial surveillance approach. Finally, it is clear that low-grade superficial bladder cancer is generally not life threatening. A compelling case is made for a “hands off” approach to these patients, rather than routine cystoscopy, intervening only for evidence of symptomatic progression (i.e., gross hematuria or voiding symptoms).
45
Readers may notice that many of the surveillance series in the literature emanate from Canada. It is possible that Canada’s socialized health care system, which is overburdened, makes conservative treatment more appealing to health care practitioners. Nonetheless, the data in each of these articles are compelling and speak for themselves. As clinicians, we have an obligation to offer the best possible care for our patients, and minimize the degree to which reimbursement and resource issues influence patient decision making. We also have an obligation to use health care resources wisely. Both of these obligations are met by the active surveillance approach described in this series. This provocative series of articles, linked by the common theme of active surveillance with selective delayed intervention for progression, represents a unique contribution to the literature. Laurence Klotz, M.D. Division of Urology Sunnybrook & Women’s College Health Sciences Centre Toronto, Ontario, Canada
Seminar section introduction
Active surveillance for genitourinary cancer: An overview Look There he is now, look: There is no interrogation in his eyes Or in the hands, quiet over the horse’s neck, And the eyes watchful, waiting, perceiving indifferent. O hidden under the dover’s wing, hidden in the turtle’s breast . . . —T.S. Elliot 20th Century approach to cancer: Seek and Destroy 21st Century approach to cancer: Target and Control —A. von Eschenbach, Director, NCI
Site by site in genitourinary oncology, a management strategy of surveillance with selective intervention for progression has become established as a valid treatment option. The surveillance approach is usually adopted because of evidence in a site that treatment is not substantially altering the natural history of disease in some patients. In urologic cancer, this concept is more prevalent at the favorable end of the spectrum, where earlier diagnosis, improved imaging, and more aggressive biopsy strategies have resulted in the detection of many nonlife-threatening cancers. There is a range of scenarios in uro-oncology in which skepticism about the value of routine intervention is warranted. These scenarios include: clinical stage 1 testicular cancer, in which retroperitoneal lymph node dissection has a 70% chance of being pathologically negative; indolent prostate cancer, which is not destined to progress during the patient’s lifetime; the Papillary Urothelial Neoplasm of Low Malignant Potential, which carries essentially no risk of metastasis or progression; and the small, incidentally discovered renal mass in an elderly patient. The surveillance approach, with selective delayed intervention for evidence of progression, has the potential to be a cancer treatment strategy for a wide range of malignancies. The concept is consistent the Dr. Von Eschenbach’s view, previously mentioned, that the future of cancer treatment will involve a more nuanced and personalized approach, using molecular, biochemical, and imaging parameters to individualize therapy. The analogy of barnyard animals in a pen is relevant. Life in the barnyard represents local disease; escape outside the fence equates to metastasis. The turtles, which remain in the yard, are optimally treated with surveillance; they will remain stable and show no tendency to metastases. The 1078-1439/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved.
birds fly away early and are also reasonably treated with initial surveillance. For patients with highly metastatic lesions that spread shortly after inception, aggressive local therapy is not likely to alter the outcome. (These patients will receive palliative therapy upon progression.) The rabbits, which hop around inside the yard for a while before jumping out, are the only ones who benefit from early detection and treatment. The limitation is that differentiating accurately between rabbits and turtles in cancer may not be easy. The close surveillance of favorable risk disease to enhance this distinction is a compelling concept. This means incorporating natural history into the decision algorithm, with selective delayed intervention for the subset with rabbit-like features. To extend the analogy, the concept is to tailor surveillance for each turtle-like cancer so that as soon as it is found to have a furry white tail, definitive therapy is implemented. Active surveillance as a model for cancer treatment is only appropriate when certain cancer and treatment characteristics are present. These characteristics include the ability to identify patients who are likely to have indolent cancer or benign disease, in a disease in which slow growth is common. There must be a method to identify patients with progressive disease. There must be significant adverse effects of treatment and evidence that delayed treatment is still effective for those who need it. Surveillance may also be reasonable based on patient characteristics, even if these criteria are not fulfilled. Patients with a limited life expectancy based on age and/or comorbidity, relative to the usual natural history of that patient’s cancer, are obvious candidates. These criteria are met to various degrees in prostate, testis, renal, and bladder cancer. In this series, the case for active surveillance with selective delayed intervention is made for each of these cancers. In prostate cancer, the problem of over-treatment of indolent disease is incontrovertible, and the case for surveillance of patients with favorable risk disease is compelling. In this series, we have included 2 perspectives on active surveillance: the “Hopkins” view, which is strongly supportive of the concept in very carefully select patients; and the “Toronto” view, which takes a more “aggressive” stance toward surveillance in terms of considering a larger proportion of patients to be appropriate candidates. In testis cancer, the disease is rap-
L. Klotz / Urologic Oncology: Seminars and Original Investigations 24 (2006) 44 – 45
idly growing and life threatening, but the opportunity provided by effective salvage therapy for patients who have recurrence enhances the appeal of an initial surveillance approach. The case for surveillance for both seminoma and nonseminoma is made in 2 separate, definitive articles. The article on renal cancer surveillance describes the marked stage migration that has occurred as a result of the routine use of abdominal imaging. This has resulted in many cases being diagnosed that would not have been identified before death in a previous era. Recent data suggest that like prostate cancer, many small renal tumors behave in a very indolent fashion and may not require treatment; the ones that progress are still amenable to cure. In addition, a significant proportion proves to be benign, further strengthening the value of an initial surveillance approach. Finally, it is clear that low-grade superficial bladder cancer is generally not life threatening. A compelling case is made for a “hands off” approach to these patients, rather than routine cystoscopy, intervening only for evidence of symptomatic progression (i.e., gross hematuria or voiding symptoms).
45
Readers may notice that many of the surveillance series in the literature emanate from Canada. It is possible that Canada’s socialized health care system, which is overburdened, makes conservative treatment more appealing to health care practitioners. Nonetheless, the data in each of these articles are compelling and speak for themselves. As clinicians, we have an obligation to offer the best possible care for our patients, and minimize the degree to which reimbursement and resource issues influence patient decision making. We also have an obligation to use health care resources wisely. Both of these obligations are met by the active surveillance approach described in this series. This provocative series of articles, linked by the common theme of active surveillance with selective delayed intervention for progression, represents a unique contribution to the literature. Laurence Klotz, M.D. Division of Urology Sunnybrook & Women’s College Health Sciences Centre Toronto, Ontario, Canada