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or lymphovascular invasion
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J.P. Richie / Urologic Oncology: Seminars and Original Investigations 24 (2006) 170 –176
The authors have used 14 population-based cancer registries from Canada, Denmark, Finland, Norway, Sweden, and the United States, to evaluate more than 40,000 men who were more than one-year survivors after treatment for testicular malignancy. Second solid malignancies were diagnosed in 2,285 patients, for an observed-to-expected ratio of 1.41. A strong decrease of both the excess relative risk and excess absolute risk of second malignancy was noted with increasing age at testicular cancer diagnosis. The authors observed a statistically significant increased risk of malignant mesothelioma in testis cancer survivors. Cumulative risks of solid cancer 40 years later— for a patient diagnosed with testis tumor at age 35—were 36% and 31% for seminomas and nonseminomatous tumors, respectively, compared with 23% for the general population. This important study, with a large number of patients and long-term follow-up, focuses on some of the late implications of treatment for patients with testicular cancer. doi:10.1016/j.urolonc.2006.01.003 Jerome P. Richie, M.D. A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: a medical research council trial. Mead GM, Cullen MH, Huddart R, Harper P, Rustin GJ, Cook PA, Stenning SP, Mason M, MRC Testicular Tumour Working Party, Medical Oncology Unit, Southampton General Hospital, Southampton, United Kingdom. Br J Cancer 2005;93:178 – 84 This phase II trial describes the use of TIP chemotherapy (paclitaxel, ifosfamide and cisplatin) as salvage for patients with metastatic germ cell cancer (GCC) who have failed initial BEP (bleomycin, etoposide and cisplatin) chemotherapy. Patients with first relapse following BEP for metastatic GCC, confirmed by biopsy or sequentially rising markers, received four courses of TIP (paclitaxel 175 mg m⫺2 day 1, followed on days 1–5 by ifosfamide 1 g m⫺2 intravenously (i.v.) and cisplatin 20 mg2 i.v.) at 3-weekly intervals. The primary outcome measure was response to TIP. In all, 51 patients were registered, of whom 43 were eligible for response assessment. Eight achieved complete remission (CR) and 18 a partial remission with negative markers (PR⫺ve); favourable response rate (FRR ⫽ CR ⫹ PR⫺ve) 60%, 95% CI (44 –75%); survival at 1 year was 70% (56 – 84%) and failure-free survival 36% (22–50%). In the group of 26 patients meeting the ‘good-risk’ criteria described by the Memorial Hospital, the FRR was 73% (52– 88%) compared with 41% (18 – 67%) for the 17 ‘poor-risk’ patients. These results are inferior to those previously reported for TIP in a single-centre study when it was given more intensively, at higher dose and with growth factor support. Nonetheless, TIP as described here can cure a substantial proportion of patients.
Commentary Although primary chemotherapy is generally effective in patients with metastatic germ cell tumor, approximately 10 –15% of patients may relapse and require salvage therapy. This is a relatively heterogeneous group of patients, some of whom can be salvaged by surgical approaches. Most patients, however, will require supplemental chemotherapy. The authors have utilized paclitaxel, ifosfamide, and cisplatin (TIP) as second-line chemotherapy in patients with relapse after prior bleomycin, etoposide, and platinum chemotherapy. Fifty-one patients from 14 centers in the United Kingdom were accrued from 1998 to 2002. Patients received 4 courses of TIP. Complete response was noted in only 8 of 43 evaluable patients and partial remission was seen in 18 of 43 patients, for an overall response rate of 60%. This multicenter study reports results that are less robust in terms of response than those at single institution centers. Nonetheless, TIP as second-line therapy is reasonable for the majority of patients who relapse after primary chemotherapy. doi:10.1016/j.urolonc.2006.01.004 Jerome P. Richie, M.D.
Retroperitoneal lymph node dissection in patients with low stage testicular cancer with embryonal carcinoma predominance and/or lymphovascular invasion. Stephenson AJ, Bosl GJ, Bajorin DF, Stasi J, Motzer RJ, Sheinfeld J, Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers and Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY. J Urol 2005;174:557– 60 Purpose: The outcome after primary retroperitoneal lymph node dissection (RPLND) was analyzed in patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer with embryonal carcinoma predominance (ECP) or lymphovascular invasion (LVI). Materials and Methods: Between 1989 and 2002, 267 patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer, and ECP and/or LVI underwent RPLND. Patient information was obtained from a prospective database. Median followup was 53 months. Results: Overall 42% of patients had pathological stage (PS) II disease, of whom 54% had low volume (PN1) disease and 16% had retroperitoneal teratoma. The 5-year progression-free probability was 90% overall, 90% for PS I and 86% for PN1. All patients with relapse were continuously free of disease following standard chemotherapy with or without resection of residual masses and the 10-year actuarial overall survival was 100%. When adjuvant chemotherapy was restricted to patients with PN2 disease, the estimated 5-year relapse rate was 9% and an estimated 72% of patients avoided chemotherapy.
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Conclusions: The low risk of systemic relapse in patients with PS I and PN1 after RPLND alone combined with the 16% incidence of retroperitoneal teratoma and the favorable morbidity profile supports RPLND over primary chemotherapy for the treatment of patients with low stage disease with ECP and/or LVI who are not candidates for surveillance. An estimated 72% of patients are spared the potential toxicity of chemotherapy if adjuvant therapy is restricted to patients with PN2. After primary RPLND and selective adjuvant chemotherapy late recurrence is distinctly uncommon and long-term cancer control is anticipated in essentially all patients.
Commentary This article looks at the benefit of RPLND in patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer with a predominance of embryonal cell cancer and/or lymphovascular invasion. Patients with these tumor parameters are universally not considered as candidates for surveillance alone. Based upon a retrospective review of 267 patients, the authors conclude that RPLND is a more effective therapeutic approach compared to primary chemotherapy. They recommend that in pN⫹ patients, adjuvant chemotherapy can be avoided in the pN1 patients with only a 9% probability of relapse. This avoids chemotherapy in 71% of pN⫹ patients. In light of an overall 100% 10-year actuarial survival with this approach, RPLND seems to be the appropriate primary therapy for this highly selective patient population because it avoids the potential of long-term side effects from chemotherapy in about three-fourths of patients without sacrificing treatment efficacy. doi:10.1016/j.urolonc.2006.01.005 Randall G. Rowland, M.D., Ph.D. Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. Fossa SD, Chen J, Schonfeld SJ, McGlynn KA, McMaster ML, Gail MH, Travis LB, Department of Clinical Cancer Research, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway. J Natl Cancer Inst 2005;97:1056 – 66 Background: Although risk estimates for synchronous and metachronous contralateral testicular cancers vary widely, many clinicians recommend routine biopsy of the contralateral testis for patients diagnosed with unilateral testicular cancer. We evaluated the risk of contralateral testicular cancer and survival in a large population-based cohort of men diagnosed with testicular cancer before age 55 years. Methods: For 29,515 testicular cancer cases reported to the National Cancer Institute’s Surveillance, Epidemiology and End Results Program from 1973 through 2001, we estimated the prevalence of synchronous contralateral testicular cancer, the observed-to-expected ratio (O/E) and 15-year cumulative risk of metachronous contralateral testicular cancer, and the 10-year overall survival rate of both synchronous and metachronous contralateral testicular cancer, using the Kaplan-Meier method for the two latter assessments. Age-adjusted multivariable analyses were used to examine risk according to histologic type of the original cancer. Results: A total of 175 men presented with synchronous contralateral testicular cancer; 287 men developed metachronous contralateral testicular cancer (O/E ⫽ 12.4 [95% confidence interval {CI} ⫽ 11.0 to 13.9]; 15-year cumulative risk ⫽ 1.9% [95% CI ⫽ 1.7% to 2.1%]). In the multivariable analysis, only nonseminomatous histology of the first testicular cancer was associated with a statistically significantly decreased risk of metachronous contralateral testicular cancer (hazard ratio [HR] ⫽ 0.60, 95% confidence interval [CI] ⫽ 0.46 to 0.79; P⬍.001). Increasing age at first testicular cancer diagnosis was associated with decreasing risk of nonseminomatous metachronous contralateral testicular cancer (odds ratio ⫽ 0.90, 95% CI ⫽ 0.86 to 0.94). The 10-year overall survival rate after metachronous contralateral testicular cancer diagnosis was 93% (95% CI ⫽ 88% to 96%), and that after synchronous contralateral testicular cancer was 85% (95% CI ⫽ 78% to 90%). Conclusions: The low cumulative risk of metachronous contralateral testicular cancer and favorable overall survival of patients diagnosed with metachronous contralateral testicular cancer is in accordance with the current U.S. approach of not performing a biopsy on the contralateral testis.
Commentary In the Scandanavian countries, physicians have favored biopsy of the contralateral testis in patients. In the United States, careful observation of the contralateral testis has been the rule. This report reviews 29,515 U.S. patients with testicular cancer listed in the NCI’s SEER database from 1973 to 2001. A total of 175 men presented with synchronous bilateral testicular tumors while 287 developed metachronous testicular tumors. The overall 15-year cumulative risk of a contralateral testicular tumor was 1.9%. Multivariant analysis showed that nonseminomatous primary tumor pathology was a predictor of a lower rate of development of metachronous testicular tumors than in patients with seminoma as the first tumor. Based on a 93% overall 10-year survival rate in patients with metachronous tumors versus an 85% rate for patients with synchronous testicular tumors, the authors conclude that the U.S. practice of observation of the contralateral testis is justified based on the excellent overall results. doi:10.1016/j.urolonc.2006.01.006 Randall G. Rowland, M.D., Ph.D.
J.P. Richie / Urologic Oncology: Seminars and Original Investigations 24 (2006) 170 –176
The authors have used 14 population-based cancer registries from Canada, Denmark, Finland, Norway, Sweden, and the United States, to evaluate more than 40,000 men who were more than one-year survivors after treatment for testicular malignancy. Second solid malignancies were diagnosed in 2,285 patients, for an observed-to-expected ratio of 1.41. A strong decrease of both the excess relative risk and excess absolute risk of second malignancy was noted with increasing age at testicular cancer diagnosis. The authors observed a statistically significant increased risk of malignant mesothelioma in testis cancer survivors. Cumulative risks of solid cancer 40 years later— for a patient diagnosed with testis tumor at age 35—were 36% and 31% for seminomas and nonseminomatous tumors, respectively, compared with 23% for the general population. This important study, with a large number of patients and long-term follow-up, focuses on some of the late implications of treatment for patients with testicular cancer. doi:10.1016/j.urolonc.2006.01.003 Jerome P. Richie, M.D. A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: a medical research council trial. Mead GM, Cullen MH, Huddart R, Harper P, Rustin GJ, Cook PA, Stenning SP, Mason M, MRC Testicular Tumour Working Party, Medical Oncology Unit, Southampton General Hospital, Southampton, United Kingdom. Br J Cancer 2005;93:178 – 84 This phase II trial describes the use of TIP chemotherapy (paclitaxel, ifosfamide and cisplatin) as salvage for patients with metastatic germ cell cancer (GCC) who have failed initial BEP (bleomycin, etoposide and cisplatin) chemotherapy. Patients with first relapse following BEP for metastatic GCC, confirmed by biopsy or sequentially rising markers, received four courses of TIP (paclitaxel 175 mg m⫺2 day 1, followed on days 1–5 by ifosfamide 1 g m⫺2 intravenously (i.v.) and cisplatin 20 mg2 i.v.) at 3-weekly intervals. The primary outcome measure was response to TIP. In all, 51 patients were registered, of whom 43 were eligible for response assessment. Eight achieved complete remission (CR) and 18 a partial remission with negative markers (PR⫺ve); favourable response rate (FRR ⫽ CR ⫹ PR⫺ve) 60%, 95% CI (44 –75%); survival at 1 year was 70% (56 – 84%) and failure-free survival 36% (22–50%). In the group of 26 patients meeting the ‘good-risk’ criteria described by the Memorial Hospital, the FRR was 73% (52– 88%) compared with 41% (18 – 67%) for the 17 ‘poor-risk’ patients. These results are inferior to those previously reported for TIP in a single-centre study when it was given more intensively, at higher dose and with growth factor support. Nonetheless, TIP as described here can cure a substantial proportion of patients.
Commentary Although primary chemotherapy is generally effective in patients with metastatic germ cell tumor, approximately 10 –15% of patients may relapse and require salvage therapy. This is a relatively heterogeneous group of patients, some of whom can be salvaged by surgical approaches. Most patients, however, will require supplemental chemotherapy. The authors have utilized paclitaxel, ifosfamide, and cisplatin (TIP) as second-line chemotherapy in patients with relapse after prior bleomycin, etoposide, and platinum chemotherapy. Fifty-one patients from 14 centers in the United Kingdom were accrued from 1998 to 2002. Patients received 4 courses of TIP. Complete response was noted in only 8 of 43 evaluable patients and partial remission was seen in 18 of 43 patients, for an overall response rate of 60%. This multicenter study reports results that are less robust in terms of response than those at single institution centers. Nonetheless, TIP as second-line therapy is reasonable for the majority of patients who relapse after primary chemotherapy. doi:10.1016/j.urolonc.2006.01.004 Jerome P. Richie, M.D.
Retroperitoneal lymph node dissection in patients with low stage testicular cancer with embryonal carcinoma predominance and/or lymphovascular invasion. Stephenson AJ, Bosl GJ, Bajorin DF, Stasi J, Motzer RJ, Sheinfeld J, Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers and Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY. J Urol 2005;174:557– 60 Purpose: The outcome after primary retroperitoneal lymph node dissection (RPLND) was analyzed in patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer with embryonal carcinoma predominance (ECP) or lymphovascular invasion (LVI). Materials and Methods: Between 1989 and 2002, 267 patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer, and ECP and/or LVI underwent RPLND. Patient information was obtained from a prospective database. Median followup was 53 months. Results: Overall 42% of patients had pathological stage (PS) II disease, of whom 54% had low volume (PN1) disease and 16% had retroperitoneal teratoma. The 5-year progression-free probability was 90% overall, 90% for PS I and 86% for PN1. All patients with relapse were continuously free of disease following standard chemotherapy with or without resection of residual masses and the 10-year actuarial overall survival was 100%. When adjuvant chemotherapy was restricted to patients with PN2 disease, the estimated 5-year relapse rate was 9% and an estimated 72% of patients avoided chemotherapy.
R.G. Rowland / Urologic Oncology: Seminars and Original Investigations 24 (2006) 170 –176
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Conclusions: The low risk of systemic relapse in patients with PS I and PN1 after RPLND alone combined with the 16% incidence of retroperitoneal teratoma and the favorable morbidity profile supports RPLND over primary chemotherapy for the treatment of patients with low stage disease with ECP and/or LVI who are not candidates for surveillance. An estimated 72% of patients are spared the potential toxicity of chemotherapy if adjuvant therapy is restricted to patients with PN2. After primary RPLND and selective adjuvant chemotherapy late recurrence is distinctly uncommon and long-term cancer control is anticipated in essentially all patients.
Commentary This article looks at the benefit of RPLND in patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer with a predominance of embryonal cell cancer and/or lymphovascular invasion. Patients with these tumor parameters are universally not considered as candidates for surveillance alone. Based upon a retrospective review of 267 patients, the authors conclude that RPLND is a more effective therapeutic approach compared to primary chemotherapy. They recommend that in pN⫹ patients, adjuvant chemotherapy can be avoided in the pN1 patients with only a 9% probability of relapse. This avoids chemotherapy in 71% of pN⫹ patients. In light of an overall 100% 10-year actuarial survival with this approach, RPLND seems to be the appropriate primary therapy for this highly selective patient population because it avoids the potential of long-term side effects from chemotherapy in about three-fourths of patients without sacrificing treatment efficacy. doi:10.1016/j.urolonc.2006.01.005 Randall G. Rowland, M.D., Ph.D. Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. Fossa SD, Chen J, Schonfeld SJ, McGlynn KA, McMaster ML, Gail MH, Travis LB, Department of Clinical Cancer Research, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway. J Natl Cancer Inst 2005;97:1056 – 66 Background: Although risk estimates for synchronous and metachronous contralateral testicular cancers vary widely, many clinicians recommend routine biopsy of the contralateral testis for patients diagnosed with unilateral testicular cancer. We evaluated the risk of contralateral testicular cancer and survival in a large population-based cohort of men diagnosed with testicular cancer before age 55 years. Methods: For 29,515 testicular cancer cases reported to the National Cancer Institute’s Surveillance, Epidemiology and End Results Program from 1973 through 2001, we estimated the prevalence of synchronous contralateral testicular cancer, the observed-to-expected ratio (O/E) and 15-year cumulative risk of metachronous contralateral testicular cancer, and the 10-year overall survival rate of both synchronous and metachronous contralateral testicular cancer, using the Kaplan-Meier method for the two latter assessments. Age-adjusted multivariable analyses were used to examine risk according to histologic type of the original cancer. Results: A total of 175 men presented with synchronous contralateral testicular cancer; 287 men developed metachronous contralateral testicular cancer (O/E ⫽ 12.4 [95% confidence interval {CI} ⫽ 11.0 to 13.9]; 15-year cumulative risk ⫽ 1.9% [95% CI ⫽ 1.7% to 2.1%]). In the multivariable analysis, only nonseminomatous histology of the first testicular cancer was associated with a statistically significantly decreased risk of metachronous contralateral testicular cancer (hazard ratio [HR] ⫽ 0.60, 95% confidence interval [CI] ⫽ 0.46 to 0.79; P⬍.001). Increasing age at first testicular cancer diagnosis was associated with decreasing risk of nonseminomatous metachronous contralateral testicular cancer (odds ratio ⫽ 0.90, 95% CI ⫽ 0.86 to 0.94). The 10-year overall survival rate after metachronous contralateral testicular cancer diagnosis was 93% (95% CI ⫽ 88% to 96%), and that after synchronous contralateral testicular cancer was 85% (95% CI ⫽ 78% to 90%). Conclusions: The low cumulative risk of metachronous contralateral testicular cancer and favorable overall survival of patients diagnosed with metachronous contralateral testicular cancer is in accordance with the current U.S. approach of not performing a biopsy on the contralateral testis.
Commentary In the Scandanavian countries, physicians have favored biopsy of the contralateral testis in patients. In the United States, careful observation of the contralateral testis has been the rule. This report reviews 29,515 U.S. patients with testicular cancer listed in the NCI’s SEER database from 1973 to 2001. A total of 175 men presented with synchronous bilateral testicular tumors while 287 developed metachronous testicular tumors. The overall 15-year cumulative risk of a contralateral testicular tumor was 1.9%. Multivariant analysis showed that nonseminomatous primary tumor pathology was a predictor of a lower rate of development of metachronous testicular tumors than in patients with seminoma as the first tumor. Based on a 93% overall 10-year survival rate in patients with metachronous tumors versus an 85% rate for patients with synchronous testicular tumors, the authors conclude that the U.S. practice of observation of the contralateral testis is justified based on the excellent overall results. doi:10.1016/j.urolonc.2006.01.006 Randall G. Rowland, M.D., Ph.D.