Radiotherapy for carcinoma of the bladder: a review.

Carcinoma of the bladder (CaB) is a common and important tumor in North America and Western Europe. There has been a steady increase in the incidence of CaB during the past 25 years in both of these regions with a simultaneous decrease in the mortality rates. The decrease in mortality is primarily due to an earlier diagnosis and the availability of more effective therapeutic interventions resulting from major advances in surgery and a wide use of multimodality bladder preservation therapy.The use of radiotherapy in the management of muscle-invasive CaB has undergone a major evolution. External beam radiotherapy alone is used infrequently in carefully selected patients. The same applies to the use of preoperative irradiation. Brachytherapy alone or combined with external beam radiotherapy has been used successfully in Europe but is used infrequently in North America. External beam radiotherapy is an essential component of a multimodality therapy consisting of cytoreductive surgery via transurethral resection of a bladder tumor followed by a planned combination of radiotherapy and chemotherapy. The outcomes of this bladder preservation therapy are similar to those reported in a like patient population treated with radical cystectomy. The main benefit of conservatively treated patients is functioning bladder in about 50% of those receiving conservative therapy. Radiotherapy alone or in a combination with chemotherapy remains an important and effective palliative therapy for patients with recurrent and/or metastatic CaB. Current research efforts are directed toward a better identification of important pretreatment risk factors predicting failure thus helping in a more optimal selection of patients who would benefit most from radical cystectomy or from the application of bladder preservation therapy.

Radiation oncology: contributions of the United States in the last years of the 20th century.

The advancements in radiation oncology in the past 50 years in the United States were probably more dramatic than those in the first half of the 20th century. Not only were there major technical achievements, but there was also an associated increase in the overall cure rates of cancer, from 20% at 5 years 50 years ago to now nearly 60% at 5 years. The cure rates in selected tumor sites at 5 years in 1950 and in 2000, respectively, were as follows: breast, 50% and 80%; colon and rectum, 40% and 85%; lung, 5% and 15%-20%; prostate, 40% and 80%; Hodgkin disease, 50% and more than 90%; cervix, 40% and 70%-80%; uterus (endometrium), 80% and more than 90%; bladder, 30% and 50%; head and neck, 30% and 60%; and esophagus, 2% and 15%. Much of this has been due to a broader array of techniques in radiation therapy available for treatment but also because of new emphasis on combined integrated modalitities (surgery, radiation therapy, and chemotherapy). New imaging techniques have contributed substantially, allowing better selection of patients for treatment and better selections of treatment modalities.

Carcinoma of the kidney, testis, and rare urologic malignancies.

The purpose of this symposium was to provide a forum for discussion on current information on the etiology and diagnosis of, and therapy for, tumors of the kidney, testis, and several uncommon malignancies of the genitourinary tract. The most recent contributions in epidemiology and molecular genetics were discussed with specific reference to their importance for clinical practice. Contemporary treatment approaches with the emphasis on multidisciplinary patient management of tumors commonly seen in the clinic as well as those that are only rarely diagnosed by urooncologists were presented. Major stress was given to the management optimization as it pertains to short- and long-term quality of life issues of patients treated for these tumors. Methods to reduce treatment toxicity including carcinogenic potential of chemotherapy, radiotherapy, or their combination were found to be of nearly equal importance to patient survival. Symposium participants reached consensus on a number of important points: 1) The management of patients with several malignancies discussed requires the presence of a multidisciplinary team of specialist who are interested in diagnosis and treatment of genitourinary tumors; 2) Patients managed in such an environment are expected to have optimal survival and the best possible quality of life; 3) Real advances in the management of patients can be best obtained through well-designed prospective clinical trials; and 4) There is a need for timely introduction of relevant advances in epidemiology and molecular genetics to clinics.

Plaque radiotherapy for uveal melanoma: long-term visual outcome in 1106 consecutive patients.

OBJECTIVE: To identify clinical predictive factors for visual outcome in a large series of patients who underwent plaque radiotherapy for uveal melanoma. DESIGN: Clinical factors, including patient data, tumor features, and radiation variables, were analyzed for their impact on visual acuity using Cox proportional hazards regression models. PARTICIPANTS: Patients with uveal melanoma and initial visual acuity of 20/100 or better in the affected eye who were treated with plaque radiotherapy between July 1976 and June 1992. MAIN OUTCOME MEASURES: Two end points were used to evaluate posttreatment visual acuity: (1) final visual acuity (good [20/20-20/100] vs poor [20/200 to no light perception]) and (2) loss of visual acuity (minimal [<5 lines Snellen visual acuity] vs moderate [> or = 5 lines Snellen visual acuity]). RESULTS: Of 1300 consecutive patients with uveal melanoma treated by plaque radiotherapy, 1106 had a visual acuity of 20/100 or better at the time of treatment. In this group, poor visual acuity was found in 34% at 5 years and 68% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted poor visual acuity were increasing tumor thickness, proximity to foveola of less than 5 mm, notched plaque shape, tumor recurrence, patient age 60 years or older, subretinal fluid, cobalt isotope, anterior tumor margin posterior to equator, and worse initial visual acuity. Moderate loss of visual acuity of 5 Snellen lines or more was found in 33% at 5 years and 69% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted moderate visual acuity loss included increasing tumor thickness, worse initial visual acuity, notched plaque shape, tumor recurrence, proximity to foveola of less than 5 mm, patient age of 60 years or older, subretinal fluid, and diabetes mellitus or hypertension. When analyzing visual outcome with regard to tumor thickness, ultimate poor visual acuity of 20/200 or worse at 5 years was found in 24% with a small melanoma (< or = 3.0 mm), 30% with a medium melanoma (3.1-8.0 mm), and 64% with a large melanoma (>8.0 mm). When analyzing visual outcome with regard to tumor proximity to visually important structures, tumors less than 5 mm from the optic disc or foveola demonstrated poor visual acuity in 35% at 5 years, whereas those 5 mm or more from the optic disc and foveola showed poor visual acuity in 25% at 5 years. CONCLUSIONS: Ultimate visual acuity after plaque radiotherapy for uveal melanoma depends on many factors, including patient age and general health, initial visual acuity, tumor location and size, subretinal fluid, radioactive isotope, and final tumor control. At 10 years' follow-up, 68% of patients demonstrate poor visual acuity. Visual acuity is most effectively preserved in eyes with small tumors outside a radius of 5 mm from the optic disc and foveola. Arch Ophthalmol. 2000;118:1219-1228

Radiation oncology in the third millennium.

Major changes have occurred in the last 25 years which have impacted significantly on the practice of radiation oncology. Twenty-five years ago, less than 40% of all patients had radiation therapy as a part of their management either for cure, palliation or in combination with surgery and/or chemotherapy. In 1998, about 60% of all patients had radiation therapy as a part of their treatment program either initially or at some time during the course of their disease process. Clearly, randomized clinical trials have made their contribution in cancer management but probably the most significant impact has been improving the standards of care relative to cancer treatment through better education and more cooperative efforts. It is extraordinarily difficult to predict the future for radiation oncology in the third millennium primarily because of the major changes in technology as well as the financial limitations with regards to treatment.

Survival following enucleation versus plaque radiotherapy in statistically matched subgroups of patients with choroidal melanomas: results in patients treated between 1980 and 1987.

BACKGROUND: The relative effectiveness of plaque radiotherapy and enucleation in patients with choroidal or ciliochoroidal melanoma remains controversial. Most published comparative survival studies have evaluated clearly biased groups, short-term follow-up, or both. METHODS: The authors performed a retrospective, non-randomized, comparative survival study on 734 patients with a choroidal or ciliochoroidal melanoma treated by enucleation (n=237) or plaque radiotherapy (n=497) between July 1980 and June 1985, and on a residual group of 448 patients, 103 treated by enucleation and 345 treated by plaque radiotherapy, identified by variable-by-variable range matching. Melanoma-specific mortality and all-cause mortality were evaluated by the life-table method. RESULTS: The melanoma-specific mortality rate was substantially worse in the original enucleation subgroup throughout available post-treatment follow-up; however, differences in baseline prognostic factors between the subgroups are likely to explain much of the survival differential. After eliminating patients with nonoverlapping values of individual clinical variables to adjust for recognized intergroup differences at baseline, there was no significant difference in the mortality curves of the residual subgroups. The cumulative 15-year survival based on deaths from metastatic melanoma in the enucleation subgroup was 57.1% (standard error=6.4%), while that in the plaque radiotherapy subgroup was 61.8% (standard error=3.3%). CONCLUSION: On the basis of these results, we conclude that a large difference in survival between equivalent groups of patients with primary choroidal or ciliary body melanoma treated by enucleation or by plaque radiotherapy appears unlikely.

Radiation retinopathy following plaque radiotherapy for posterior uveal melanoma.

OBJECTIVE: To identify the risk factors that lead to the development of radiation retinopathy following plaque radiotherapy for posterior uveal melanoma. Radiation retinopathy is a slowly progressive, occlusive vasculopathy characterized by radiation-induced endothelial damage. METHODS: Review of the medical records of patients with posterior uveal melanoma treated with plaque radiotherapy. RESULTS: Of 1300 patients with posterior uveal melanoma treated with plaque radiotherapy from July 1, 1976, through June 30, 1992, radiation retinopathy developed in 560 (43.1%). By using Kaplan-Meier survival estimates, we found that 5% of the patients had nonproliferative radiation retinopathy at 1 year (95% confidence interval [CI], 3%-6%) and 42% at 5 years (95% CI, 38%-45%). The proportion of patients with proliferative retinopathy was 1% at 1 year (95% CI, 0.2%-1.5%) and 8% at 5 years (95% CI, 5%-10%). Multivariate analyses showed that the subset of clinical variables best related to the development of nonproliferative radiation retinopathy were tumor margin of less than 4 mm from foveola (P<.001), tumor limited to the choroid (P = .002), and radiation dose rate of greater than 260 cGy/h to the tumor base (P = .02). The best subset of independent variables related to the development of radiation maculopathy were tumor of less than 4 mm to foveola (P<.001) and the use of radioisotope iridium 192 (192Ir) (P = .02) compared with iodine 125 (125I). From a multivariate model, the most important factors for the development of proliferative radiation retinopathy included diabetes mellitus (P = .01), radioisotope 192Ir (P = .01) compared with 125I, and tumor base of greater than 10 mm (P = .02). CONCLUSIONS: Radiation retinopathy is a common finding after plaque radiotherapy for choroidal melanoma, occurring in 42% of patients at 5 years. The main predictors of radiation retinopathy are posterior tumor location with margin near the foveola and high radiation dose rate to the tumor base.

Radiation complications and tumor control after plaque radiotherapy of choroidal melanoma with macular involvement.

PURPOSE: To determine the outcome of plaque radiotherapy in the treatment of macular choroidal melanoma and to identify the risk factors associated with the development of radiation complications, tumor recurrence, and metastasis. METHODS: Chart analysis of 630 consecutive patients (630 eyes) with macular choroidal melanoma managed by plaque radiotherapy between July 1976 and June 1992. RESULTS: The median largest basal tumor diameter was 10 mm, and the median tumor thickness was 4 mm. By means of Kaplan-Meier estimates, visually significant maculopathy developed at 5 years in 40% of the patients, cataract in 32%, papillopathy in 13%, and tumor recurrence in 9%. Vision decrease by 3 or more Snellen lines was found in 40% of the patients at 5 years. Sixty-nine eyes (11%) were enucleated because of radiation complications and recurrence. Twelve percent of the patients developed metastasis by 5 years and 22% by 10 years. Results of multivariate Cox proportional hazards analyses showed that the significant predictors for tumor recurrence were a distance of tumor margin from the optic disk of less than 2 mm (P = .003) and retinal invasion (P = .009). The significant variables that were predictive of metastasis included tumor thickness greater than 4 mm (P = .02) and largest basal tumor diameter greater than 10 mm (P = .03). CONCLUSIONS: Plaque radiotherapy offers a 91% 5-year local tumor control rate for macular choroidal melanoma. Despite good local tumor control, the risk for metastasis is 12% at 5 years and 22% at 10 years. In 11% of the patients, enucleation eventually became necessary because of radiation complications and tumor recurrence.

Plaque radiotherapy of uveal melanoma with predominant ciliary body involvement.

BACKGROUND: There are several options for management of ciliary body melanoma, including plaque radiotherapy, charged particle irradiation, local resection, and enucleation. The choice of therapy depends on many factors, and plaque radiotherapy is often used. OBJECTIVES: To determine the outcome of plaque radiotherapy in the management of ciliary body melanoma and to identify the risk factors associated with the development of radiation complications, tumor recurrence, metastasis, and melanoma-related death after plaque radiotherapy of ciliary body melanoma. METHODS: We analyzed the clinical records of 136 patients with ciliary body melanoma who were treated with plaque radiotherapy between July 1976 and June 1992. RESULTS: The median follow-up period was 70 months. Using Kaplan-Meier survival estimates, the most frequent radiation complication at 5 years' follow-up was cataract, developing in 48% of the patients, followed by neovascular glaucoma (21%), retinopathy (20%), scleral necrosis (12%), and vitreous hemorrhage (11%). Visual acuity decrease (by > or =3 Snellen lines) was noted in 40% of the patients at 5 years. Kaplan-Meier estimates showed that 8% of the patients developed recurrence, 28% had metastasis, and 22% died of melanoma-related causes by 5 years. Univariate analysis demonstrated that the factors predictive of radiation cataract were superonasal (P = .003) and inferior tumor meridian (P = .02) compared with inferonasal meridian and apex dose rate greater than 57 cGy/h (P = .05). The development of neovascular glaucoma was significantly related to iris involvement with the ciliary body tumor (P<.001). The factors predictive of development of radiation retinopathy were base dose rate greater than 230 cGy/h (P = .03) and the presence of diabetes mellitus (P = .05). The only predictor of metastasis was tumor thickness greater than 7 mm (P = .02). The risk factors for melanoma-related death were the presence of metastasis (P<.001), tumor thickness greater than 7 mm (P = .02), and recurrence (P = .02). Multivariate analyses showed that the most significant variables predictive of the development of scleral necrosis were intraocular pressure greater than 15 mm Hg (P<.001) and tumor thickness greater than 7 mm (P = .007). The most significant predictive factors for vitreous hemorrhage were visual acuity of 20/40 to 20/200 (P = .02) and intraocular pressure greater than 15 mm Hg (P = .02). The best subset of independent predictors of vision decrease were mushroom tumor shape (P = .002), age older than 61 years (P = .006), and superonasal meridian (P = .04). The risks for melanoma-related death were presence of metastasis (P<.001) and tumor thickness greater than 7 mm (P = .01). There was no group of significant variables predictive for radiation cataract, neovascular glaucoma, retinopathy, tumor recurrence, and metastasis in multivariate analysis. CONCLUSIONS: Plaque radiotherapy offers 92% 5-year local control rate for ciliary body melanoma. Metastasis occurs in 28% of the patients treated with this method by 5 years. Patients with tumors greater than 7 mm in thickness are at greater risk than patients with thinner tumors for metastatic disease and melanoma-related death. Major radiation complications include radiation cataract, neovascular glaucoma, retinopathy, and scleral necrosis.

Long-term survival in choroidal and ciliary body melanoma after enucleation versus plaque radiation therapy.

OBJECTIVE: This study aimed to determine whether the long-term melanoma-specific mortality rate of patients with a primary choroidal or ciliary body melanoma treated by enucleation is appreciably lower than that of similar patients treated by plaque radiation therapy. DESIGN: Retrospective, nonrandomized, comparative clinical trial. PARTICIPANTS: A previously reported group of 237 patients, 140 treated by enucleation and 97 treated by cobalt-60 (Co-60) plaque between May 1976 and June 1980, and a residual group of 122 patients, 51 treated by enucleation and 71 treated by Co-60 plaque, were identified by variable-by-variable range matching. INTERVENTION: Primary treatment by enucleation or Co-60 plaque radiation therapy was performed. MAIN OUTCOME MEASURES: Melanoma-specific mortality and duration of post-treatment survival were measured. RESULTS: The melanoma-specific mortality rate was substantially worse in the original enucleation subgroup over the entire 15-year follow-up interval; however, differences in baseline prognostic factors between the subgroups are likely to explain the difference in survival curves. After elimination of patients with nonoverlapping values of individual clinical variables to adjust for recognized intergroup differences at baseline, there was no significant or clinically important difference in the 15-year mortality curves of the residual subgroups. The relative rate ratio for the treatment effect in the residual patients was 0.97 (95% confidence interval, 0.51-1.86). There was no late downturn in the survival curve of the plaque-treated patients or late crossing of the curves. CONCLUSION: A large difference in survival between equivalent groups of patients with primary choroidal or ciliary body melanoma treated by enucleation versus plaque radiation therapy appears to be unlikely.

Management of carcinoma of the bladder.

Carcinoma of the bladder (CaB) is a common tumor of the genitourinary tract. In the United States in 1997, CaB was second in frequency of occurrence and third in mortality among genitourinary tumors. This tumor has a well-documented history of environmental and industrial causative factors. The strongest etiologic risk factors include the use of tobacco, which is thought to be responsible for half of the CaB diagnosed in men in the United States, and some arylamines. In the past 30 years, there has been major improvement in the survival of patients with this disease. Multiple factors were responsible for this accomplishment and they include: 1) better understanding of the natural history of CaB, 2) development of immunohistochemical analysis helpful in defining prognostic factors, 3) improved imaging and nonimaging diagnostic modalities helpful in making earlier diagnosis and better defining the true anatomical extent of the tumor, 4) development of more effective therapy for carcinoma in situ, 5) major improvement in surgical techniques resulting in better treatment outcomes, and 6) the wide use of adjuvant chemotherapy. Major stress has been placed on the quality of life of patients treated for CaB. Quality of life was improved by optimizing surgical, radiation, and medical treatment techniques. The two most important factors producing this quality-of-life improvement include: 1) the use of organ-preserving therapy in properly selected patients that involves the use of a multimodality therapeutic approach with transurethral resection, radiation therapy, and chemotherapy; and 2) the ability to treat selected men and women with radical cystectomy followed by orthotopic reconstruction that allows patients nearly physiologic voiding. Current research efforts are directed toward better patient selection for appropriate therapy which is expected to increase patient survival and improve quality of life. Of particular importance in the selection of this optimal therapy in patients with CaB is a wide application in the clinical practice of important recent advances in molecular genetics.

Monoclonal antibodies in the treatment of metastatic carcinoma to the liver: updated report of a pilot study including leukapheresis.

Twenty-two patients who had failed conventional treatment for advanced colorectal carcinoma metastatic to the liver were entered in this study. Survival from the date the hepatic disease was documented and ranged from 3 to 62 months, with an average of 20 months. Notably, 8 of the 22, or 36%, lived 24 months or more. Four patients, or 18%, survived 3 to 5 years after diagnosis of hepatic metastasis.