Increasing prostate-specific antigen profile following definitive radiation therapy for localized prostate cancer: clinical observations.

PURPOSE: To examine the natural history of patients who have received definitive radiation therapy alone for clinically localized prostate cancer and have an increasing prostate-specific antigen (PSA) profile. PATIENTS AND METHODS: One hundred fifty-one men with an increasing PSA profile after definitive radiotherapy were identified. The subsequent natural history of these men, including local recurrence, distant metastasis, and survival, was examined. In 119 men, posttreatment PSA doubling times (PSADT) were calculated using linear regression. Cox regression models were used to examine the effect of clinical and treatment variables on clinical failure and survival. RESULTS: Patients with high pretreatment PSA values, high Gleason scores, and T3 tumors were more likely to develop a PSA elevation. The median calculated post-treatment PSADT was 13 months, and 95% of patients had posttreatment PSADT of less than 3 years. PSADT was correlated with tumor stage and Gleason score. Five years after PSA elevation, the estimated rate of clinical local recurrence is 26% and the estimated rate of distant metastases is 47%. Rapid PSADT (< 12 months) and a short interval from the end of treatment to PSA elevation (< 12 months) were significant independent predictors of distant metastases. The estimated rates of overall and cause-specific survival 5 years after PSA elevation are 65% and 76%, respectively. Gleason grade is the only significant independent predictor of overall and cause-specific survival after PSA elevation. CONCLUSION: The natural history of men who have an increasing PSA profile following definitive radiotherapy is heterogeneous. In the absence of salvage therapy, at least three quarters of men will have clinical evidence of recurrent disease 5 years after a PSA elevation is detected. Men with a rapid posttreatment PSADT and a short interval from the end of treatment to an increasing PSA profile are at a very high risk of developing distant metastasis within 5 years of PSA elevation.

Localized prostate cancer treated by external-beam radiotherapy alone: serum prostate-specific antigen--driven outcome analysis.

PURPOSE: To determine the 5-year rate of survival with no evidence of disease (NED) using strict biochemical criteria in men with prostate cancer treated by external-beam radiotherapy alone and to examine possible clinical and treatment factors that predict the likelihood of NED survival. MATERIALS AND METHODS: Five hundred men with clinically localized prostate cancer consecutively treated with external-beam radiotherapy alone with no prior, concomitant, or adjuvant endocrine therapy were identified. All patients had serial serum prostate-specific antigen (PSA) values determined after treatment and 451 patients had pretreatment PSA values determined. The median follow-up duration is 20 months (range, 2 to 72; mean, 36). RESULTS: The 5-year rate of overall survival in this group of patients was 80%. The 5-year rate of survival without clinical evidence of disease (cNED) was 72%. The 5-year rate of survival without evidence of clinical, radiographic, or biochemical relapse (bNED) was 51%. Multivariate analysis demonstrated that a pretreatment serum PSA level < or = 15 ng/mL was the most important predictor of bNED survival (P < .0001). Patients with early-stage (T1, T2a/b) tumors and a pretreatment serum PSA less than 15 ng/mL had a 3-year rate of bNED survival of 86%. The rate of bNED survival for patients with a pretreatment PSA level greater than 15 ng/mL was 38% at 3 years. CONCLUSION: Pretreatment serum PSA level is the most important predictor of treatment outcome in this group of patients treated with definitive radiotherapy alone. External-beam radiation alone can produce acceptable early rates of bNED survival in patients with clinically organ-confined tumors and a pretreatment PSA level < or = 15 ng/mL. To produce acceptable results in those patients with pretreatment PSA levels more than 15 ng/mL, effective adjuvant treatments in addition to aggressive local treatments are necessary.

Patterns-of-failure analysis of patients with high pretreatment prostate-specific antigen levels treated by radiation therapy: the need for improved systemic and locoregional treatment.

PURPOSE: The patterns of failure (local and/or regional v metastatic) have been determined for patients with prostate cancer and pretreatment prostate-specific antigen (PSA) levels > or = 20 ng/mL treated with radiation alone with the purpose to design appropriate multimodal treatments. MATERIALS AND METHODS: One hundred twenty patients with pretreatment PSA levels > or = 20 ng/mL were treated with external-beam radiation alone between February 1988 and October 1993. They were arbitrarily divided by PSA levels, 20 to 29.9 ng/mL, 30 to 49.9 ng/mL, and > or = 50 ng/mL, and analyzed in terms of freedom from any failure (no evidence of biochemical disease [bNED], and PSA level < 1.5 ngm/mL and not increasing), as well as freedom from imaging evidence of distant metastasis (fdm). RESULTS: There was no significant difference in short-term outcome by pretreatment PSA level, and thus all patients were pooled for analysis. At 4 years, 81% were fdm and 28% were free of any failure. This suggests that approximately 50% have recurred with local and/or regional disease or undetectable metastatic disease. Multivariate analysis indicated that low palpation stage and higher center of prostate dose were associated with better bNED survival. Multivariate analysis indicated that increasing stage and younger age are significantly associated with increasing distant metastasis. CONCLUSION: Patients with pretreatment PSA levels > or = 20 ng/mL are not optimally treated by irradiation alone. The pattern of failure suggests improvement may come from systemic treatment of metastatic disease and high-dose radiation to improve locoregional disease. To evaluate this, we have begun a multimodal trial of chemohormonal therapy followed by extended-field irradiation.

Impact of improved irradiation technique, age, and lymph node sampling on the severe complication rate of surgically staged endometrial cancer patients: a multivariate analysis.

PURPOSE: Limited information is available regarding factors that predispose to complications following postoperative pelvic radiotherapy (RT) for endometrial cancer. To address this issue, patients with clinically staged I/II endometrial cancer who received postoperative RT following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) with or without lymph node sampling (LNS) were studied. PATIENTS AND METHODS: From 1960 through 1990, 235 patients with adenocarcinoma of the endometrium received postoperative RT after surgical staging. Multiple factors were evaluated to determine associations with severe complications. Pretreatment factors included age, stage, comorbidities. Treatment-related factors consisted of LNS, total RT dose, volume of RT fields, dose per fraction, total number of RT fields, number of RT fields treated per day, machine energy, and addition of vaginal implant. RESULTS: The 5-year actuarial risk of a severe complication was 5.5%. Factors associated with an increased risk of complications in univariate analysis included age more than 65 years (11% v 2%), use of only one portal per day (40% v 3%), use of anteroposterior/posteroanterior fields (23% v 4%), total dose > or = 50 Gy (8% v 2%), and LNS (11% v 3%). In a multivariate analysis, only older age, LNS, and the use of one field per day were significant. Increased risks associated with a total dose > or 50 Gy and the anteroposterior/posteroanterior technique were entirely attributable to the use of one field per day. A subanalysis among patients who had adequate RT techniques (eg, multiple fields treated per day) showed a significant increase in complications (7% v 1%) for those with and without LNS, respectively. CONCLUSIONS: Severe complications associated with adjuvant RT for endometrial cancer were increased among patients who were older or underwent LNS or received suboptimal RT technique. Pelvic RT using proper methods can be delivered with acceptable risks.

Outcome of patients receiving radiation for cancer of the esophagus: results of the 1992-1994 Patterns of Care Study.

PURPOSE: A Patterns of Care Study examined the records of patients with esophageal cancer (EC) treated with radiation in 1992 through 1994 to determine the national practice processes of care and outcomes and to compare the results with those of clinical trials. PATIENTS AND METHODS: A national survey of 63 institutions was conducted using two-stage cluster sampling, and specific information was collected on 400 patients with squamous cell (62%) or adenocarcinoma (37%) of the thoracic esophagus who received radiation therapy (RT) as part of primary or adjuvant treatment. Patients were staged according to a modified 1983 American Joint Committee on Cancer staging system. Fifteen percent of patients had clinical stage (CS) I disease, 40% had CS II disease, and 30% had CS III disease. Twenty-six percent of patients underwent esophagectomy. Seventy-five percent of patients received chemotherapy; 84% of these received concurrent chemotherapy and radiation (CRT). RESULTS: Significant variables for overall survival in multivariate analysis include the use of esophagectomy (risk ratio [RR] = 0.62), the use of chemotherapy (RR = 0.63), Karnofsky performance status (KPS) greater than 80 (RR = 0.61), CS I or II disease (RR = 0.66), and facility type (RR = 0.72). Age, sex, and histology were not significant. Preoperative CRT resulted in a nonsignificantly higher 2-year survival rate compared with definitive CRT alone (63% v 39%; P =.11), whereas 2-year survival by planned treatment rather than treatment given was 47.7% for preoperative CRT and 35.4% for definitive CRT (P =.23). Definitive CRT compared with definitive RT alone resulted in significantly higher 2-year survival (39% v 20.6%; P =.027) and lower 2-year local regional failure (30% v 57.9%; P =. 0031). CONCLUSION: This study confirms the value of CRT in EC treatment. It indicates that the results obtained in practice settings nationwide are similar to those obtained in clinical trials and that KPS and the 1983 clinical staging system are useful prognostic indicators. The suggested value of esophagectomy and superiority of preoperative CRT over CRT alone in this study should be tested in a randomized trial.

Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: Radiation Therapy Oncology Group Trial 92-02.

PURPOSE: The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT) -treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. PATIENTS AND METHODS: There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. RESULTS: Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P =.08), BF (P =.0445), DM (P <.0001), CSD (P <.0001), and OD (P =.0094). When categoric variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The 7.1% cut point was related to BF (P =.09), DM (P =.0008), and CSD (P =.017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. CONCLUSION: Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.

Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31.

PURPOSE: Although androgen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate, its potential value as an adjuvant has not been substantiated. MATERIALS AND METHODS: In 1987, the Radiation Therapy Oncology Group (RTOG) initiated a randomized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients had been accessioned to the study. Of these, 945 remained analyzable: 477 on the adjuvant arm and 468 on the observation arm. RESULTS: Actuarial projections show that at 5 years, 84% of patients on the adjuvant goserelin arm and 71% on the observation arm remain without evidence of local recurrence (P < .0001). The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% (P < .001) and 60% and 44% (P < .0001). If prostate-specific antigen (PSA) level greater than 1.5 ng is included as a failure (after > or = 1 year), the 5-year disease-free survival rate on the adjuvant goserelin arm is 53% versus 20% on the observation arm (P < .0001). The 5-year survival rate (for the entire population) is 75% on the adjuvant arm versus 71% on the observation arm (P = .52). However, in patients with centrally reviewed tumors with a Gleason score of 8 to 10, the difference in actuarial 5-year survival (66% on the adjuvant goserelin arm v 55% on the observation arm) reaches statistical significance (P = .03). CONCLUSION: Application of androgen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression. At this point, with a median follow-up time of 4.5 years, a significant improvement in survival has been observed only in patients with centrally reviewed tumors with a Gleason score of 8 to 10.

Single-photon emission computed tomography and positron-emission tomography assays for tissue oxygenation.

Radiotherapy prescription can now be customized to target the major mechanism(s) of resistance of individual tumors. In that regard, functional imaging techniques should be exploited to identify the dominant mechanism(s). Tumor biology research has identified several mechanisms of tumor resistance that may be unique to radiation treatments. These fall into 3 broad areas associated with (1) tumor hypoxic fraction, (2) tumor growth rate, (3) and the intrinsic radiosensitivity of tumor clonogens. Imaging research has markers in various stages of development for quantifying relevant information about each of these mechanisms, and those that measure tumor oxygenation and predict for radioresistance are the most advanced. Positron-emission tomography (PET) measurement of oxygen 15 has yielded important information, particularly about brain tissue perfusion, metabolism, and function. Indirect markers of tumor hypoxia have exploited the covalent binding of bioreductive intermediates of azomycin-containing compounds whose uptakes are inversely proportional to intracellular oxygen concentrations. Pilot clinical studies with single-photon emission computed tomography (SPECT) and PET detection of radiolabeled markers to tumor hypoxia have been reported. Recently, other studies have attempted to exploit the reduction properties of both technetium and copper chelates for the selective deposition of radioactive metals in hypoxic tissues. A growing number of potentially useful isotopes are now available for labeling several novel chemicals that could have the appropriate specificity and sensitivity. Preclinical studies with "microSPECT" and "microPET" will be important to define the optimal radiodiagnostic(s) for measuring tissue oxygenation and for determining the time after their administration for optimal hypoxic signal acquisition. Radiolabeled markers of growth kinetics and intrinsic radiosensitivity of cells in solid tumors are also being developed. We conclude that radiation oncology is uniquely positioned to benefit from functional imaging markers that identify important mechanisms of tumor radioresistance, since several strategies for overcoming these individual mechanisms have already been identified.

The crisis in health care cost in the United States: some implications for radiation oncology.

This communication reviews the increasing cost of medical care in the USA (13% of GNP in 1995) and the associated lack of access to care for 35 million citizens. Factors affecting cost and access are presented, including where the increases are seen. The resulting effects on the Federal government, private industry, the patient, and the physician are noted. The failure of a current mechanism of control of cost is illustrated as are the views of patients and physicians. The portion of radiation oncology devoted to palliative care is discussed for its potential to reduce costs by $150-$250 million through the elimination of excessive treatments and thereby contribute to the solution of excessive cost of care.

Future plans for quality assurance in radiation oncology in the United States.

The Patterns of Care Study (PCS) is conducting continuing surveys in key disease sites that will monitor changes in processes and outcome of care from 1973 to 1985. The PCS will conduct a process survey in 1984 that will provide the baseline data for the quality assessment survey program available to individual facilities in the United States in 1985. This program will be conducted through the American College of Radiology and operated by the joint ACR-ASTR Quality Assessment Committee which includes representatives from the American Association of Physicists in Medicine. It will be a voluntary program that will be paid for by the facility requesting assessment. The feedback will be confidential and constructed in a manner as to maximally help the facility recognize areas where improvements can be made. We are continuing to work with licensing accrediting groups such as the Joint Commission on Accreditation of Hospitals (JCAH) and the American College of Surgeons' cancer accreditation program to advise them of the service we will be providing, and to obtain their recognition and recommendation of this service. This program will provide a means of meaningful quality assessment for the individual facility, and the opportunity for each facility to improve the quality of their care. In addition, through these surveys we will continue to monitor changes in the national benchmarks for processes and outcomes of care of key disease sites in which radiation therapy plays an important interventional role.

Complications from large field intermediate dose infradiaphragmatic radiation: an analysis of the patterns of care outcome studies for Hodgkin's disease and seminoma.

There are only infrequent complications from intermediate dose infradiaphragmatic radiation to the para-aortics or para-aortic and iliac nodal regions as given in Hodgkin's disease or seminoma. Nonetheless, such complications can cause significant debility and may be lifelong. Treatment related factors associated with such complications should be identified and where possible, avoided. We have analyzed the records of 1,026 patients treated nationwide in the Patterns of Care Outcome. Studies including the Hodgkin's national practice survey (387 patients), Hodgkin's large facility survey (253 patients), and Seminoma national practice survey (386 patients). There were 883 patients who received infradiaphragmatic radiation to the para-aortics or para-aortic and iliac regions. Complications which occurred in these patients included gastrointestinal injury, hepatitis, nephritis, gonadal injury, hematopoietic injury, second malignancy, and miscellaneous others. There were 139 complications of any severity and 35 major complications requiring hospitalization for management. The 3-year actuarial complication rates were 14% and 4% for any and major complications, respectively. There was a statistically significant increase in both any complications and major complications with dose (p less than .01). The most frequent complications were those related to gastrointestinal injury such as peptic ulceration, hemorrhage, chronic diarrhea, and intestinal obstruction. Major bowel complications comprised 60% (21/35) of major complications and increased with dose from 1% for doses less than 3,500 cGy to 3% for doses greater than or equal to 3,500 cGy (p = .03). This study indicates that total dose is an important factor in determining complications, particularly gastrointestinal injury, in patients receiving infradiaphragmatic radiation in Hodgkin's disease and seminoma and that prior G.I. disease is associated with an increased risk of radiation related bowel complication. The radiotherapist should seek to optimize the therapeutic ratio in these diseases where gross disease can be controlled with 3500 cGy or less with few exceptions.

A comparison of the cost of various treatment methods for early cancer of the prostate.

The relative costs have been determined for treating prostate cancer by radical prostatectomy, lymph node dissection with I125 implant, and external beam radiation in a large community practice. About 15% of patients were treated with the options involving surgery. The median cost of radical prostatectomy was $14,400, lymph dose dissection and I125 implant $12,000, and external beam radiation $6750 prior to October 1984 and $5600 after October 1984. None of the data indicate superior outcome by any one of these methods for Stage A or B prostate cancer. Therefore, the surgical approaches are usually not recommended except for the patient highly motivated to maintain potency who may select the I125 implant. In an era of diminishing funds for health care, the federal government, industry, and perceptive HMO's may elect to pay only for the less expensive method.

The need for subspecialization: intraoperative radiation therapy.

Intraoperative radiation therapy represents a technically complex branch of radiation oncology which is undergoing intensive study. Further results of randomized Phase III trials must be available before IORT is established as an effective modality. The majority of residency training programs do not have IORT available and the use of IORT is not required for initial certification in radiation oncology. Residents could be educated in the principal concepts and the technical details of IORT and should be knowledgeable in the results of clinical trials in IORT. At the present time the leading investigators in IORT should consider offering a special research year or fellowship training in an appropriate residency training facility. If Phase III trials of IORT prove positive in a number of sites it is likely that this modality will become mainstream and then training in IORT should be required of all radiation oncology residents. Certainly there is insufficient evidence for subspecialty certification in IORT at the present time. However, one should not construe from this statement that special training in IORT is not required for its appropriate use. On the contrary, given the potential for morbidity and yet to be proven efficacy, special training in IORT should be undertaken in centers of excellence in IORT and patients treated with IORT should be entered in clinical trials whenever possible.

Scrutiny of the ASTRO consensus definition of biochemical failure in irradiated prostate cancer patients demonstrates its usefulness and robustness. American Society for Therapeutic Radiology and Oncology.

PURPOSE: The goals of this study are: (1) to establish the robustness of the Fox Chase Cancer Center (FCCC) and the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definitions of failure by comparing biochemical estimates under various modifications of the censoring and failure time components to their respective unaltered definitions; (2) to isolate the source of variation between the two definitions of failure; and (3) to describe the hazard of failure over time for each definition. METHODS: Between May 1989 and May 1997, 670 men were treated at Fox Chase Cancer Center for localized prostate cancer using three-dimensional conformal radiation therapy (3DCRT). These men were stratified into three groups for analysis: 111 men treated with adjuvant hormones; 204 men treated with radiation therapy alone and presenting with more favorable prognosis tumor characteristics; 255 men treated with radiation therapy alone and presenting with less favorable prognosis tumor characteristics. For each group, biochemical failure was estimated and compared using the FCCC and ASTRO definitions of failure. The robustness of each definition was evaluated by comparing estimates under the definition as stated to those under various modifications of the censoring and failure components. Analyses were also performed while excluding slow-progressing patients. To isolate the source of variation between the two failure definitions, estimates were compared for patients with agreement in failure status. Estimates of biochemical failure, and thus hazard rates, were made using Kaplan-Meier methodology. RESULTS: ASTRO biochemical failure estimates were higher than the FCCC failure estimates in the first 5 years post-treatment. Beyond 5 years, ASTRO estimates level off, while the FCCC failure estimates continued to increase. These failure patterns were similar in all patient groups; however, patients treated with adjuvant hormones had a much higher risk of failure immediately following treatment under the ASTRO definition. Modifying the censoring pattern had little effect on failure estimates in any patient group, regardless of definition used. The exclusion of patients with slow prostate-specific antigen (PSA) doubling time did not result in biochemical estimates that differed significantly from those for all patients. The analysis of patients with agreement in failure status continued to demonstrate significant differences in estimates between the two definitions, and thus differences may be attributed to the specification of time to failure. For all patient groups, hazard rates were dependent upon failure definition: under the FCCC failure definition, patients were at constant risk of failure over the observation period; under the ASTRO failure definition, patients were at risk of failure during the first 4 years following treatment, and then at low risk of failure beyond 5 years. CONCLUSIONS: Both FCCC and ASTRO failure definitions were robust to modifications in censoring and the inclusion of patients with long doubling times. The ASTRO failure definition was robust to specifying the time to failure at first rise, as opposed to midway between nadir and first rise. Similarities in estimates for all patients versus patients with agreeing failure status suggest that differences in failure definition lie in the specification of time to failure. The ASTRO definition of failure is more appropriate because it does not impose an empirical failure marker but is based on the initiation of biochemical rise. The use of the ASTRO consensus definition demonstrated little risk of biochemical failure 4 years beyond treatment. The ASTRO failure definition should be adopted in all research involving biochemical failure analysis of men treated with radiation therapy.

Therapeutic options in the management of incidental carcinoma of the prostate.

Incidental carcinoma of the prostate is a protean disease with a natural course which may be indolent or aggressive, with prognosis correlated with histologic grade and extent of disease. Treatment of this pathologic entity has varied over time and has been governed by institutional policy rather than randomized comparison of therapies. This report reviews the literature on incidental prostate cancer focusing on outcomes of patients as related to different therapeutic maneuvers. Observation alone with careful follow-up is appropriate therapy only for those patients with well differentiated disease of limited extent. Patients with diffuse or less differentiated disease required definitive therapy to prevent symptomatic progression. Hormonal manipulation alone has not been demonstrated to be of benefit. Radioactive implants have yielded poor disease-free survival. Radical prostatectomy by an experienced surgeon for patients with adequate health to tolerate the procedure has been associated with acceptable morbidity and excellent local control and survival. Radiation therapy has yielded similar excellent local control and survival and appears to be appropriate for a broader range of patients regardless of health or age.

Quality assurance in radiation therapy: clinical and physical aspects. Consensus of best current management: the starting point for clinical quality assessment.

Consensus of best current management developed by a rational and deliberative process can provide the basis for clinical quality assessment. Unfortunately, it is not always possible to arrive at a consensus at all cancer sites, and this generally indicates areas where clinical research is needed. Assessing the quality of care in these situations presents special problems. When it is possible to arrive at consensus in a specific disease, this consensus should detail appropriate pretreatment evaluation and the details of the treatment. Committees of experts for each specific disease site can formulate the consensus and must document their decisions based on information from the current world literature. A carefully thought out and documented consensus can then provide the basis for the development of process based questionnaires in assessing quality. We have observed that individuals formulating consensus of best current management do not strictly follow their own criteria, and that compliance in various strata of practice throughout the United States shows a greater deviation from consensus than anticipated and indeed this deviation crosses all types of practice. It was then necessary to conduct outcome surveys in the same patients to validate the processes of care by showing a correlation of process performance with outcome or indeed to change our concepts of best current management. We recognize from these outcome studies that relatively few processes have direct association with outcome and the majority of our consensus points relate to either good general patient management or items important to individual patients but not to large groups of patients. In addition to validating processes through outcome correlations, we have found that process verification is important. We have observed quite different outcomes for two groups of patients with Hodgkin's disease treated with the same processes (i.e., mantle field technology and adequate radiation dose, etc.). We were unable to identify the reason for an increased failure rate in one group of these patients until we looked at each individual mantle port film from the two groups of patients. We then identified that one facility was not including the Hodgkin's disease in the treatment portal due to poor technical performance. We believe that this program of process verification may be important in evaluating quality for any disease site. Data will be presented that illustrates the above problems.

The structure of radiation oncology practices in the continental United States.

The American College of Radiology periodically collects data on radiation oncology facilities with megavoltage equipment. The results of the 1986 survey are summarized, with specific reference to the substantial growth in free-standing facilities.

Seminoma of the testis: long-term beneficial and deleterious results of radiation.

PURPOSE: The followup of 387 patients in a USA national survey of seminoma treated with radiation in 1973 and 1974 has been extended beyond 15 years to assess the long-term benefits and problems resulting from treatment. RESULTS: Survival at 15 years is 83% for Stage I, 68% for Stage II; freedom from recurrence at 15 years is 93% for Stage I, 96% for Stage II; NED survival at 15 years is 80% for Stage I, 68% for Stage II; cause specific freedom from cancer death is 98% for Stage I and 97% for Stage II at 15 years. Second malignancy rates were 8% at 15 years, and observed in 14 patients versus 4.2 expected (p < .001). Deaths due to these second cancers were also increased with seven observed versus two expected (p < .01). Non-cancer intercurrent disease death occurred in 23 patients versus 7.5 expected (p < .01). The most frequent cause was cardiac death which appeared in 10 patients versus 4.4 expected (p < .05) and 8 of the 10 patients received mediastinal radiation. Two additional patients died of pulmonary fibrosis after mediastinal radiation. Mediastinal radiation correlated with all intercurrent disease and cardio-pulmonary deaths (p < .05), but not with second malignancies. With the exception of one, all patients experiencing cardiac death after mediastinal irradiation were 40 years or older at the time of treatment, with a range of 32-58 years and a mean interval to death of 9.8 years. CONCLUSIONS: Recommendations for the future management of seminoma include: reducing the irradiated volume in the treatment of Stage I patients, completely eliminating mediastinal radiation in the treatment of patients with Stage IIA seminoma and treating patients with Stage IIB seminoma with chemotherapy. Radiation dose should not exceed 30 Gy for Stage I or 35 Gy for Stage IIA.

Pretreatment prostate-specific antigen values in patients with prostate cancer: 1989 patterns of care study process survey.

PURPOSE: A Patterns of Care Study (PCS) national survey was conducted to show the national averages for processes of radiation therapy care for prostate cancer patients in 1989. In the current study we report an analysis of pretreatment prostate-specific antigen (PSA) by stage, grade, and ethnic origin. METHODS AND MATERIALS: Process data were collected from 672 patients treated in 1989 at 71 separate institutions. Four hundred and twenty-seven (64%) of these patients had a pretreatment PSA value recorded. Three hundred and forty-three of the 427 patients were treated with external beam irradiation alone and were selected for the current analysis. The 1992 AJCC staging system was used. RESULTS: There was a significant increase in pretreatment PSA with increasing stage. The median values of PSA were 8.3 ngm/ml in the T1 group (n = 65), 11.2 ngm/ml in the T2 group (n = 178), and 20.9 ngm/ml in the T3 group (n = 90) (p < 0.001). Ten patients were not staged. There was a significant increase in pretreatment PSA with decreasing differentiation. The median pretreatment PSA was 9.7 ngm/ml in well-differentiated tumors (n = 109), 13.0 ngm/ml in moderately differentiated tumors (n = 163), and 22.0 ngm/ml in poorly differentiated tumors. (n = 61) (p < 0.001). Ten patients had no differentiation recorded. African Americans (24) showed a significant increase in pretreatment PSA compared to Caucasians (304). The respective medians were 23.2 ng/ml and 11.9 ng/ml (p = 0.04). They also show more poorly differentiated tumors (33% vs. 17%) and more T3 tumors (46% vs. 25%). Other minorities, although small in number (n = 9) were similar to African Americans. CONCLUSION: Pretreatment PSA levels were established for patients treated with external beam irradiation in 1989 in the United States. They increase with stage and decreasing differentiation. African Americans and other minorities show a doubling of median values compared to Caucasians' pretreatment PSA with an increase in stage and grade. The adverse prognosis observed for African Americans is predicted by their pretreatment PSA. The cause of this PSA elevation is not known and may be related to lack of access to care or to a more aggressive biology for prostate cancer in African Americans.

Localization of the prostatic apex for radiation treatment planning.

PURPOSE: To determine whether retrograde urethrogram, or the combination of computed tomography (CT) scan/retrograde urethrogram is more accurate for locating the magnetic resonance imaging (MRI) designated prostatic apex, and to determine whether patients treated in our department with CT/urethrogram are receiving the prescribed minimal dose to the MRI identified prostatic apex. METHODS AND MATERIALS: Seventeen patients with early stage prostate cancer were enrolled in a prospective study to determine the location of the prostatic apex. All of the patients agreed to undergo MRI in addition to retrograde urethrogram, and CT of the pelvis for three dimensional (3D) treatment planning. The prostatic apex was identified on each of the studies and measured from a reference point (the most superior portion of the pubic symphysis). The location of the prostatic apex as measured by retrograde urethrogram alone and by CT/urethrogram was compared to the location of the prostatic apex as measured by MRI. Because of MRI's ability for multiplanar capabilities, and high soft tissue contrast in the region of the prostate, it was assumed to be more accurate for identifying the location of the prostatic apex, and was used as the gold standard. RESULTS: The location of the prostatic apex as determined by the urethrogram alone was on average 5.8 mm caudad to the location on MRI (p = 0.012), while the location of the prostatic apex as determined by CT/urethrogram was 3.1 mm caudad to the location on MRI (p = 0.150). If the prostatic apex is defined at 12 mm instead of 10 mm above the urethrogram tip, the statistically significant difference between the urethrogram and the MRI is no longer present. Based on these results, all 17 patients received the minimum prescribed dose to the prostatic apex. CONCLUSION: CT/urethrogram correlates better with the location of the MRI determined prostatic apex, than does the urethrogram alone. Locating the prostatic apex 12 mm above the urethrogram tip better localizes the prostatic apex, while also avoiding the error that can potentially lead to a geographic miss. This in fact assures that all of our patients receive the minimum prescribed dose to this critical site of extraprostatic extension, while also decreasing the amount of normal tissue that is included in the treatment volume.