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Radical Irradiation and Misonidazole in the Treatment of T2 Grade III and T3 Bladder Cancer
ONCOLOGY AND CHEMOTHERAPY concomitant urothelial dysplasia are predictive of recurrence and those tumors with concomitant carcinoma in situ indicate a serious prognosis. Whether these high risk patients should be treated with topical chemotherapy or cystectomy still is undetermined. F. T. A. 3 figures, 4 tables, 10 references
Postoperative Radiation Therapy for Muscle-Invading Bladder Carcinoma G. KOPELSON AND J. A. HEANEY, Departments of Therapeutic Radiology and Urology, Tufts University School of Medicine and Tufts-New England Medical Center, Boston, Massachusetts J. Surg. Oncol., 23: 263-268 (Aug.) 1983
411
cardiac causes but was found to have a superficial tumor at death. Neurotoxicity was seen with the higher dose of misonidazole. In the second group 16 of 22 patients (73 per cent) were free of disease at 6 months. Of 16 patients followed 12 to 26 months 10 (62 per cent) continue to be free of disease and 3, who failed the combined therapy, were treated with salvage cystectomy. The comparative figures in the retrospective study demonstrate a 43 per cent rate free of disease at 6 to 12 months. These data show a statistically significant improved rate free of disease at 6 months in the second group of patients compared to those treated with radiotherapy alone. Lastly, evaluation of the misonidazole blood levels demonstrates that, when given intravesically, the drug seems to be effective topically rather than systemically. 2 tables, 13 references
There is scant literature on the role of postoperative radiation therapy for high risk bladder cancer patients. The authors have presented their experience with such management in terms of disease control and complications. From 1974 to 1980, 15 patients with muscle-invading bladder carcinoma received adjuvant postoperative radiation therapy. The initial bladder operation varied from total cystectomy to transurethral resection of the bladder tumor. The planned radiation treatment was 4,000 to 5,000 rad to the pelvis in 5 to 6 weeks followed by a bladder boost in patients who did not undergo cystectomy. Survival at 2 and 5 years was 54 and 27 per cent, respectively. Complications included chronic diarrhea and small bowel. obstruction in 2 patients. The authors concluded that postoperative radiation may be useful in the multimodality management of patients with bladder carcinoma, especially those identified as high risk after pathological staging and initial operation. N. V. R. 1 figure, 4 tables, 29 references
Abstracter's comment. Although the study ofradiosensitizers, such as misonidazole, seems impressive it is important to note that the 6-month landmark in such patients is woefully inadequate. The patients with stage T2 or T3 bladder cancer must be followed for ~2 to 3 years to be able to compare differences in local therapy. Finally, these studies still do not address the problem of unrecognized systemic disease occurring in approximately 50 per cent of such patients. J. D. S.
Radical Irradiation and Misonidazole in the Treatment of T2 Grade III and T3 Bladder Cancer
Int. J. Androl., 6: 229-234 (June) 1983
R. P. ABRATT, R. SEALY, T. D. TUCKER, M.A. WILLIAMS, D. R. BARNES, M. B. JOHNSON, J. A. S. GREEN AND J. S. CRIDLAND, Departments of Radiotherapy, Urology and Pharmacology, Groote Schuur Hospital, Cape Town, Department of Radiotherapy, Frere Hospital, Provincial Hospital and Livingston Hospital, Port Elizabeth and University of Cape Town, Cape Town, South Africa
Int. J. Rad. Oncol. Biol. Phys., 9: 629-632 (May) 1983 Misonidazole is a radiosensitizing agent of hypoxic cells that has an affinity for electrons and can diffuse into the hypoxic portions of tumors. The authors have designed 2 pilot studies for the use of misonidazole in patients with invasive bladder cancer and compared the early results to those in 69 patients (historical controls) treated with definitive radiotherapy only. In the first pilot study misonidazole was given orally 4 hours before large doses of cobalt radiation at a dose of 3.0 to 4.5 gm./m. 2 • Of 11 patients treated 7 were evaluable for study. In the second group additional misonidazole was given intravesically at a dose of 1.0 gm. diluted in 30 to 40 cc and introduced into the bladder 2 hours before the radiotherapy. The bladder was drained of the agent just before radiation treatment. There were 22 patients evaluable in this study. Both groups of patients received 5,200 rad. Of 7 patients in the first group 5 are free of disease at 26 to 38 months, 1 died with persistent local cancer and 1 died of
Carcinoma In Situ of Germ Cells and Subsequent Development of an Invasive Seminoma in a Hyperprolactinaemic Man H. ISHIDA, K. NOMURA AND
ISURUGI, T. NIIJIMA, K. MATSUMOTO, K. K. HIROSE, Department of Urology, University of Tokyo, Department of Urology and Neurobrain Surgery, National Cancer Center, Department of Urology, Tokyo Metropolitan Bokuto Hospital and Department of Urology, Showa University, Tokyo, Japan
Intratubular atypical germ cells have been recognized in testicular tissue adjacent to seminomatous and nonseminomatous germ cell tumors. These cells also have been found in the contralateral testis of men with such tumors, in ectopic testes and in the testes of infertile men. One hypothesis is that such atypical germ cells may represent a form of carcinoma in situ from which germ cell tumors may originate directly. The authors report a case that they believe supports this assumption. A 25-year-old patient presented initially for decreased libido and was found to have small soft scrotal testes. A testicular biopsy apparently was believed originally to show only atrophic seminiferous tubules. Later, these slides apparently were reviewed again (probably at the time the germ cell neoplasm was detected) and were believed to have contained foci of carcinoma in situ. The patient presented with a mass in the biopsied testicle 5 years after the biopsy, which proved to be a seminoma. Interestingly, at that time an elevated serum prolactin level was found secondary to a pituitary tumor, which presumably was responsible for the initial complaint of decreased libido.
Abstracter's comment. Regardless of the details in this particular case and the question of whether the initial biopsy actually could have been a harbinger of subsequent tumor, the question of carcinoma in situ of the testis, referring to intratubular, noninvasive, atypical germ cells, must be considered carefully. Is there, indeed, such a histological appearance that can be agreed upon by all pathologists? If so, what is the true
Postoperative Radiation Therapy for Muscle-Invading Bladder Carcinoma G. KOPELSON AND J. A. HEANEY, Departments of Therapeutic Radiology and Urology, Tufts University School of Medicine and Tufts-New England Medical Center, Boston, Massachusetts J. Surg. Oncol., 23: 263-268 (Aug.) 1983
411
cardiac causes but was found to have a superficial tumor at death. Neurotoxicity was seen with the higher dose of misonidazole. In the second group 16 of 22 patients (73 per cent) were free of disease at 6 months. Of 16 patients followed 12 to 26 months 10 (62 per cent) continue to be free of disease and 3, who failed the combined therapy, were treated with salvage cystectomy. The comparative figures in the retrospective study demonstrate a 43 per cent rate free of disease at 6 to 12 months. These data show a statistically significant improved rate free of disease at 6 months in the second group of patients compared to those treated with radiotherapy alone. Lastly, evaluation of the misonidazole blood levels demonstrates that, when given intravesically, the drug seems to be effective topically rather than systemically. 2 tables, 13 references
There is scant literature on the role of postoperative radiation therapy for high risk bladder cancer patients. The authors have presented their experience with such management in terms of disease control and complications. From 1974 to 1980, 15 patients with muscle-invading bladder carcinoma received adjuvant postoperative radiation therapy. The initial bladder operation varied from total cystectomy to transurethral resection of the bladder tumor. The planned radiation treatment was 4,000 to 5,000 rad to the pelvis in 5 to 6 weeks followed by a bladder boost in patients who did not undergo cystectomy. Survival at 2 and 5 years was 54 and 27 per cent, respectively. Complications included chronic diarrhea and small bowel. obstruction in 2 patients. The authors concluded that postoperative radiation may be useful in the multimodality management of patients with bladder carcinoma, especially those identified as high risk after pathological staging and initial operation. N. V. R. 1 figure, 4 tables, 29 references
Abstracter's comment. Although the study ofradiosensitizers, such as misonidazole, seems impressive it is important to note that the 6-month landmark in such patients is woefully inadequate. The patients with stage T2 or T3 bladder cancer must be followed for ~2 to 3 years to be able to compare differences in local therapy. Finally, these studies still do not address the problem of unrecognized systemic disease occurring in approximately 50 per cent of such patients. J. D. S.
Radical Irradiation and Misonidazole in the Treatment of T2 Grade III and T3 Bladder Cancer
Int. J. Androl., 6: 229-234 (June) 1983
R. P. ABRATT, R. SEALY, T. D. TUCKER, M.A. WILLIAMS, D. R. BARNES, M. B. JOHNSON, J. A. S. GREEN AND J. S. CRIDLAND, Departments of Radiotherapy, Urology and Pharmacology, Groote Schuur Hospital, Cape Town, Department of Radiotherapy, Frere Hospital, Provincial Hospital and Livingston Hospital, Port Elizabeth and University of Cape Town, Cape Town, South Africa
Int. J. Rad. Oncol. Biol. Phys., 9: 629-632 (May) 1983 Misonidazole is a radiosensitizing agent of hypoxic cells that has an affinity for electrons and can diffuse into the hypoxic portions of tumors. The authors have designed 2 pilot studies for the use of misonidazole in patients with invasive bladder cancer and compared the early results to those in 69 patients (historical controls) treated with definitive radiotherapy only. In the first pilot study misonidazole was given orally 4 hours before large doses of cobalt radiation at a dose of 3.0 to 4.5 gm./m. 2 • Of 11 patients treated 7 were evaluable for study. In the second group additional misonidazole was given intravesically at a dose of 1.0 gm. diluted in 30 to 40 cc and introduced into the bladder 2 hours before the radiotherapy. The bladder was drained of the agent just before radiation treatment. There were 22 patients evaluable in this study. Both groups of patients received 5,200 rad. Of 7 patients in the first group 5 are free of disease at 26 to 38 months, 1 died with persistent local cancer and 1 died of
Carcinoma In Situ of Germ Cells and Subsequent Development of an Invasive Seminoma in a Hyperprolactinaemic Man H. ISHIDA, K. NOMURA AND
ISURUGI, T. NIIJIMA, K. MATSUMOTO, K. K. HIROSE, Department of Urology, University of Tokyo, Department of Urology and Neurobrain Surgery, National Cancer Center, Department of Urology, Tokyo Metropolitan Bokuto Hospital and Department of Urology, Showa University, Tokyo, Japan
Intratubular atypical germ cells have been recognized in testicular tissue adjacent to seminomatous and nonseminomatous germ cell tumors. These cells also have been found in the contralateral testis of men with such tumors, in ectopic testes and in the testes of infertile men. One hypothesis is that such atypical germ cells may represent a form of carcinoma in situ from which germ cell tumors may originate directly. The authors report a case that they believe supports this assumption. A 25-year-old patient presented initially for decreased libido and was found to have small soft scrotal testes. A testicular biopsy apparently was believed originally to show only atrophic seminiferous tubules. Later, these slides apparently were reviewed again (probably at the time the germ cell neoplasm was detected) and were believed to have contained foci of carcinoma in situ. The patient presented with a mass in the biopsied testicle 5 years after the biopsy, which proved to be a seminoma. Interestingly, at that time an elevated serum prolactin level was found secondary to a pituitary tumor, which presumably was responsible for the initial complaint of decreased libido.
Abstracter's comment. Regardless of the details in this particular case and the question of whether the initial biopsy actually could have been a harbinger of subsequent tumor, the question of carcinoma in situ of the testis, referring to intratubular, noninvasive, atypical germ cells, must be considered carefully. Is there, indeed, such a histological appearance that can be agreed upon by all pathologists? If so, what is the true