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Blood pressure and body mass index in long-term survivors of testicular cancer
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R.G. Rowland / Urologic Oncology: Seminars and Original Investigations 24 (2006) 170 –176
Modeling the cost of management options for stage I nonseminomatous germ cell tumors: a decision tree analysis. Link RE, Allaf ME, Pili R, Kavoussi LR, James Buchanan Brady Urological Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Medical Institute, Johns Hopkins Hospital, Baltimore, MD. J Clin Oncol 2005;23:5762–73 Purpose: Patients with clinical stage I nonseminomatous germ cell tumors (NSGCTs) have been managed with surveillance, chemotherapy, or retroperitoneal lymphadenectomy (RPLND) with similar survival outcomes. Cost factors influencing the choice of therapy were evaluated using computer-based decision analysis. Methods: A detailed model was developed that integrates projected costs for more than 60 possible treatment outcomes. It incorporates primary, adjuvant, and salvage chemotherapy, primary and post-chemotherapy RPLND, and both laparoscopic and open surgical approaches. Starting values and probabilities were derived from a comprehensive meta-analysis of the last 25 years of testes cancer literature. Hypothesis testing was performed using sensitivity analysis. Results: The model predicts a cost premium for both primary chemotherapy (18.7%) and RPLND (51.7%) compared with surveillance. If laparoscopic RPLND was practiced, the cost premium for primary surgery (29.1%) approached that of chemotherapy (26.4%). Open RPLND was 1.25⫻ as costly as laparoscopic RPLND, primarily because of longer hospitalization. The choice of open RPLND yielded a 6.9% cost premium for a surveillance program in this model. For such a program, primary chemotherapy became cost advantageous when the probability of recurrence during surveillance was more than 46%. Conclusion: This model allows a variety of treatment cost hypotheses to be tested. Primary RPLND is never cost advantageous over surveillance or primary chemotherapy. Surgical costs can significantly increase the overall cost of a surveillance program. In stage I patients with high-risk tumor characteristics, primary chemotherapy may have a cost advantage over surveillance.
Commentary This is a report that uses mathematical models to calculate the cost of various primary treatment approaches to clinical stage I nonseminomatous germ cell testicular cancer. The authors clearly show their methods and the source of their figures for cost calculations. They conclude that surveillance is the least costly option, followed by chemotherapy, and finally, RPLND. Further calculations looked at the costs of open versus laparoscopic RPLND. Unfortunately, the authors were unable to ascertain length of stay (LOS) information from open RPLND series at institutions with very high volume experiences. Hospital stay costs were the major contributor to the overall cost of both open and laparoscopic RPLND. The break-even cost point between open and laparoscopic RPLND was a LOS of 5 days for open surgery. The data the authors used to calculate LOS for open RPLND showed a mean LOS of 7.10 days. In this commentator’s experience at two institutions, the usual LOS after open RPLND is 3–5 days. These lower LOSs for open RPLND would change the conclusions of this article. The lower cost of RPLND would also affect the authors’ calculations concerning the risk of relapse based on tumor parameters and the point at which RPLND becomes cost effective. doi:10.1016/j.urolonc.2006.01.007 Randall G. Rowland, M.D., Ph.D. Blood pressure and body mass index in long-term survivors of testicular cancer. Sagstuen H, Aass N, Fossa SD, Dahl O, Klepp O, Wist EA, Wilsgaard T, Bremnes RM, Department of Oncology, Institute of Clinical Medicine, University of Tromso, Tromso, Norway. J Clin Oncol 2005;23:4980 –90 Purpose: To evaluate blood pressure and body mass index (BMI) in long-term survivors of testicular cancer (TC) treated with different modalities. Patients and Methods: One thousand eight hundred fourteen patients treated for unilateral TC in Norway (1980 to 1994) were invited to participate in a follow-up study (1998 to 2002), including measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), and BMI. Of these patients, 1,289 patients (71%) participated in the study. The patients were categorized into four treatment groups: surgery (n ⫽ 242), radiotherapy (n ⫽ 547), and two chemotherapy groups, cumulative cisplatin dose ⱕ850 mg (n ⫽ 402) and cumulative cisplatin dose more than 850 mg (n ⫽ 98). A control group consisted of healthy males from the Tromso Population Study (n ⫽ 2,847). Results: At diagnosis, age-adjusted regression analyses showed no differences between the treatment groups for any variables. After a median follow-up time of 11.2 years, age-adjusted SBP and DBP were significantly higher for both chemotherapy groups compared with the surgery group. Chemotherapy-treated patients had increased odds for hypertension at follow-up compared with the surgery group, and the odds were highest for the cisplatin more than 850 mg group (odds ratio ⫽ 2.4; 95% CI, 1.4 to 4.0). The cisplatin more than 850 mg group had a significantly higher 10-year BMI increase and a higher prevalence of obesity at follow-up than the surgery group. Compared with healthy controls, chemotherapy-treated patients had, at follow-up, increased SBP, increased DBP, excessive BMI increase, and a higher prevalence of hypertension. Conclusion: Five to 20 years after therapy, cured TC patients treated with cisplatin-based chemotherapy had significantly higher levels of blood pressure, a higher prevalence of hypertension, and an excessive weight gain compared with patients treated with other modalities and compared with healthy controls
R.G. Rowland / Urologic Oncology: Seminars and Original Investigations 24 (2006) 170 –176
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Commentary This report compares blood pressure, the incidence of hypertension, and body mass index (BMI) between a healthy male population and testicular cancer survivors treated by surgery, radiation or cisplatin-based chemotherapy. Patients treated with up to 850 mg of cisplatin or over 850 mg of cisplatin had a small but significant increase in systolic and diastolic blood pressure and hypertension compared to the patients treated with surgery. The higher dose chemotherapy patient group also had a significantly greater BMI than the surgery group. Chemotherapy patients had a higher systolic and diastolic blood pressure, a higher BMI increase, and a higher incidence of hypertension than control patients. These differences held true even though the healthy, control population was older than the testis cancer survivors (63 versus 44 years). If age equivalent control data were available, these data would be likely to show even greater differences. Since testosterone levels may influence BMI, the authors controlled their data for serum testosterone levels and still observed the above-noted differences. These observations may help us to further define and understand the long-term toxicity of various treatment modalities for testicular cancer. doi:10.1016/j.urolonc.2006.01.008 Randall G. Rowland, M.D., Ph.D. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP, MRC TE19 Collaborators and the EORTC 30982 Collaborators, Department of Medical Oncology, St. Bart’s and the London Hospital, London, United Kingdom. Lancet 2005;366:293–300 Background: Adjuvant radiotherapy is effective treatment for stage I seminoma, but is associated with a risk of late non-germ-cell cancer and cardiovascular events. After good results in initial studies with one injection of carboplatin, we undertook a large randomised trial to compare the approaches of radiotherapy with chemotherapy in seminoma treatment. Methods: Between 1996 and 2001, 1477 patients from 70 hospitals in 14 countries were randomly assigned to receive radiotherapy (para-aortic strip or dog-leg field; n ⫽ 904) or one injection of carboplatin (n ⫽ 573; dose based on the formula 7 ⫻ [glomerular filtration rate ⫹ 25] mg), at two trial centres in the UK and Belgium. The primary outcome measure was the relapse-free rate, with the trial powered to exclude absolute differences in 2-year rates of more than 3%. Analysis was by intention to treat and per protocol. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN27163214. Findings: 885 and 560 patients received radiotherapy and carboplatin, respectively. With a median follow-up of 4 years (IQR 3.0 – 4.9), relapse-free survival rates for radiotherapy and carboplatin were similar (96.7% [95% CI 95.3–97.7] vs. 97.7% [96.0 –98.6] at 2 years; 95.9% [94.4 –97.1] vs. 94.8% [92.5–96.4] at 3 years, respectively; hazard ratio 1.28 [90% CI 0.85–1.93], p ⫽ 0.32). At 2 years’ follow-up, the absolute differences in relapse-free rates (radiotherapy-chemotherapy) were ⫺1.0% (90% CI ⫺2.5 to 0.5) by direct comparison of proportions, and 0.9% (-0.5 to 3.0) by a hazard-ratio-based approach. Patients given carboplatin were less lethargic and less likely to take time off work than those given radiotherapy. New, second primary testicular germ-cell tumours were reported in ten patients allocated irradiation (all after para-aortic strip field) and two allocated carboplatin (5-year event rate 1.96% [95% CI 1.0 –3.8] vs. 0.54% [0.1–2.1], p ⫽ 0.04). One seminoma-related death occurred after radiotherapy and none after carboplatin. Interpretation: This trial has shown the non-inferiority of carboplatin to radiotherapy in the treatment of stage I seminoma. Although the absence of disease-related deaths and preliminary data indicating fewer second primary testicular germ-cell tumours favour carboplatin use, these findings need to be confirmed beyond 4 years’ follow-up. Commentary This study presents a prospective randomized trial of radiotherapy versus single-dose carboplatin for clinical stage I pure seminoma. With a median follow-up of 4 years, there was an approximately 1% relapse-free survival rate both at 2 and 3 years analyses (96.7% vs. 97.7% favoring carboplatin and 95.9% vs. 94.8% favoring radiation, respectively). The authors recognize that long-term follow-up is needed to see if this equivalency holds up. It should be noted that there was a lower rate of contralateral second primary germ cell testicular cancers in the chemotherapy group versus the radiotherapy group. doi:10.1016/j.urolonc.2006.01.009 Randall G. Rowland, M.D., Ph.D. Impact of the number of positive lymph nodes on disease-free survival in patients with pathological stage B1 nonseminomatous germ cell tumor. Beck SD, Foster RS, Bihrle R, Cheng L, Ulbright TM, Donohue JP, Departments of Urology and Pathology, Indiana University Medical Center, Indianapolis, IN. J Urol 2005;174:143–5 Purpose: The prognostic significance of the number of metastatic lymph nodes detected at surgery on survival is well documented for breast and colon cancer, and it has recently been reported in bladder cancer. We tested this hypothesis in patients with pathological stage B1 nonseminomatous germ cell tumor (NSGCT).
R.G. Rowland / Urologic Oncology: Seminars and Original Investigations 24 (2006) 170 –176
Modeling the cost of management options for stage I nonseminomatous germ cell tumors: a decision tree analysis. Link RE, Allaf ME, Pili R, Kavoussi LR, James Buchanan Brady Urological Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Medical Institute, Johns Hopkins Hospital, Baltimore, MD. J Clin Oncol 2005;23:5762–73 Purpose: Patients with clinical stage I nonseminomatous germ cell tumors (NSGCTs) have been managed with surveillance, chemotherapy, or retroperitoneal lymphadenectomy (RPLND) with similar survival outcomes. Cost factors influencing the choice of therapy were evaluated using computer-based decision analysis. Methods: A detailed model was developed that integrates projected costs for more than 60 possible treatment outcomes. It incorporates primary, adjuvant, and salvage chemotherapy, primary and post-chemotherapy RPLND, and both laparoscopic and open surgical approaches. Starting values and probabilities were derived from a comprehensive meta-analysis of the last 25 years of testes cancer literature. Hypothesis testing was performed using sensitivity analysis. Results: The model predicts a cost premium for both primary chemotherapy (18.7%) and RPLND (51.7%) compared with surveillance. If laparoscopic RPLND was practiced, the cost premium for primary surgery (29.1%) approached that of chemotherapy (26.4%). Open RPLND was 1.25⫻ as costly as laparoscopic RPLND, primarily because of longer hospitalization. The choice of open RPLND yielded a 6.9% cost premium for a surveillance program in this model. For such a program, primary chemotherapy became cost advantageous when the probability of recurrence during surveillance was more than 46%. Conclusion: This model allows a variety of treatment cost hypotheses to be tested. Primary RPLND is never cost advantageous over surveillance or primary chemotherapy. Surgical costs can significantly increase the overall cost of a surveillance program. In stage I patients with high-risk tumor characteristics, primary chemotherapy may have a cost advantage over surveillance.
Commentary This is a report that uses mathematical models to calculate the cost of various primary treatment approaches to clinical stage I nonseminomatous germ cell testicular cancer. The authors clearly show their methods and the source of their figures for cost calculations. They conclude that surveillance is the least costly option, followed by chemotherapy, and finally, RPLND. Further calculations looked at the costs of open versus laparoscopic RPLND. Unfortunately, the authors were unable to ascertain length of stay (LOS) information from open RPLND series at institutions with very high volume experiences. Hospital stay costs were the major contributor to the overall cost of both open and laparoscopic RPLND. The break-even cost point between open and laparoscopic RPLND was a LOS of 5 days for open surgery. The data the authors used to calculate LOS for open RPLND showed a mean LOS of 7.10 days. In this commentator’s experience at two institutions, the usual LOS after open RPLND is 3–5 days. These lower LOSs for open RPLND would change the conclusions of this article. The lower cost of RPLND would also affect the authors’ calculations concerning the risk of relapse based on tumor parameters and the point at which RPLND becomes cost effective. doi:10.1016/j.urolonc.2006.01.007 Randall G. Rowland, M.D., Ph.D. Blood pressure and body mass index in long-term survivors of testicular cancer. Sagstuen H, Aass N, Fossa SD, Dahl O, Klepp O, Wist EA, Wilsgaard T, Bremnes RM, Department of Oncology, Institute of Clinical Medicine, University of Tromso, Tromso, Norway. J Clin Oncol 2005;23:4980 –90 Purpose: To evaluate blood pressure and body mass index (BMI) in long-term survivors of testicular cancer (TC) treated with different modalities. Patients and Methods: One thousand eight hundred fourteen patients treated for unilateral TC in Norway (1980 to 1994) were invited to participate in a follow-up study (1998 to 2002), including measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), and BMI. Of these patients, 1,289 patients (71%) participated in the study. The patients were categorized into four treatment groups: surgery (n ⫽ 242), radiotherapy (n ⫽ 547), and two chemotherapy groups, cumulative cisplatin dose ⱕ850 mg (n ⫽ 402) and cumulative cisplatin dose more than 850 mg (n ⫽ 98). A control group consisted of healthy males from the Tromso Population Study (n ⫽ 2,847). Results: At diagnosis, age-adjusted regression analyses showed no differences between the treatment groups for any variables. After a median follow-up time of 11.2 years, age-adjusted SBP and DBP were significantly higher for both chemotherapy groups compared with the surgery group. Chemotherapy-treated patients had increased odds for hypertension at follow-up compared with the surgery group, and the odds were highest for the cisplatin more than 850 mg group (odds ratio ⫽ 2.4; 95% CI, 1.4 to 4.0). The cisplatin more than 850 mg group had a significantly higher 10-year BMI increase and a higher prevalence of obesity at follow-up than the surgery group. Compared with healthy controls, chemotherapy-treated patients had, at follow-up, increased SBP, increased DBP, excessive BMI increase, and a higher prevalence of hypertension. Conclusion: Five to 20 years after therapy, cured TC patients treated with cisplatin-based chemotherapy had significantly higher levels of blood pressure, a higher prevalence of hypertension, and an excessive weight gain compared with patients treated with other modalities and compared with healthy controls
R.G. Rowland / Urologic Oncology: Seminars and Original Investigations 24 (2006) 170 –176
175
Commentary This report compares blood pressure, the incidence of hypertension, and body mass index (BMI) between a healthy male population and testicular cancer survivors treated by surgery, radiation or cisplatin-based chemotherapy. Patients treated with up to 850 mg of cisplatin or over 850 mg of cisplatin had a small but significant increase in systolic and diastolic blood pressure and hypertension compared to the patients treated with surgery. The higher dose chemotherapy patient group also had a significantly greater BMI than the surgery group. Chemotherapy patients had a higher systolic and diastolic blood pressure, a higher BMI increase, and a higher incidence of hypertension than control patients. These differences held true even though the healthy, control population was older than the testis cancer survivors (63 versus 44 years). If age equivalent control data were available, these data would be likely to show even greater differences. Since testosterone levels may influence BMI, the authors controlled their data for serum testosterone levels and still observed the above-noted differences. These observations may help us to further define and understand the long-term toxicity of various treatment modalities for testicular cancer. doi:10.1016/j.urolonc.2006.01.008 Randall G. Rowland, M.D., Ph.D. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP, MRC TE19 Collaborators and the EORTC 30982 Collaborators, Department of Medical Oncology, St. Bart’s and the London Hospital, London, United Kingdom. Lancet 2005;366:293–300 Background: Adjuvant radiotherapy is effective treatment for stage I seminoma, but is associated with a risk of late non-germ-cell cancer and cardiovascular events. After good results in initial studies with one injection of carboplatin, we undertook a large randomised trial to compare the approaches of radiotherapy with chemotherapy in seminoma treatment. Methods: Between 1996 and 2001, 1477 patients from 70 hospitals in 14 countries were randomly assigned to receive radiotherapy (para-aortic strip or dog-leg field; n ⫽ 904) or one injection of carboplatin (n ⫽ 573; dose based on the formula 7 ⫻ [glomerular filtration rate ⫹ 25] mg), at two trial centres in the UK and Belgium. The primary outcome measure was the relapse-free rate, with the trial powered to exclude absolute differences in 2-year rates of more than 3%. Analysis was by intention to treat and per protocol. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN27163214. Findings: 885 and 560 patients received radiotherapy and carboplatin, respectively. With a median follow-up of 4 years (IQR 3.0 – 4.9), relapse-free survival rates for radiotherapy and carboplatin were similar (96.7% [95% CI 95.3–97.7] vs. 97.7% [96.0 –98.6] at 2 years; 95.9% [94.4 –97.1] vs. 94.8% [92.5–96.4] at 3 years, respectively; hazard ratio 1.28 [90% CI 0.85–1.93], p ⫽ 0.32). At 2 years’ follow-up, the absolute differences in relapse-free rates (radiotherapy-chemotherapy) were ⫺1.0% (90% CI ⫺2.5 to 0.5) by direct comparison of proportions, and 0.9% (-0.5 to 3.0) by a hazard-ratio-based approach. Patients given carboplatin were less lethargic and less likely to take time off work than those given radiotherapy. New, second primary testicular germ-cell tumours were reported in ten patients allocated irradiation (all after para-aortic strip field) and two allocated carboplatin (5-year event rate 1.96% [95% CI 1.0 –3.8] vs. 0.54% [0.1–2.1], p ⫽ 0.04). One seminoma-related death occurred after radiotherapy and none after carboplatin. Interpretation: This trial has shown the non-inferiority of carboplatin to radiotherapy in the treatment of stage I seminoma. Although the absence of disease-related deaths and preliminary data indicating fewer second primary testicular germ-cell tumours favour carboplatin use, these findings need to be confirmed beyond 4 years’ follow-up. Commentary This study presents a prospective randomized trial of radiotherapy versus single-dose carboplatin for clinical stage I pure seminoma. With a median follow-up of 4 years, there was an approximately 1% relapse-free survival rate both at 2 and 3 years analyses (96.7% vs. 97.7% favoring carboplatin and 95.9% vs. 94.8% favoring radiation, respectively). The authors recognize that long-term follow-up is needed to see if this equivalency holds up. It should be noted that there was a lower rate of contralateral second primary germ cell testicular cancers in the chemotherapy group versus the radiotherapy group. doi:10.1016/j.urolonc.2006.01.009 Randall G. Rowland, M.D., Ph.D. Impact of the number of positive lymph nodes on disease-free survival in patients with pathological stage B1 nonseminomatous germ cell tumor. Beck SD, Foster RS, Bihrle R, Cheng L, Ulbright TM, Donohue JP, Departments of Urology and Pathology, Indiana University Medical Center, Indianapolis, IN. J Urol 2005;174:143–5 Purpose: The prognostic significance of the number of metastatic lymph nodes detected at surgery on survival is well documented for breast and colon cancer, and it has recently been reported in bladder cancer. We tested this hypothesis in patients with pathological stage B1 nonseminomatous germ cell tumor (NSGCT).