Real-World Practice Patterns and Predictors of Continuous versus Intermittent Androgen Deprivation Therapy Use for Prostate Cancer in Older Men.

PURPOSE: Phase-III randomized control trial evidence suggests intermittent androgen deprivation therapy (IADT) is not significantly inferior to continuous androgen deprivation therapy (ADT) for patients with prostate cancer (PC). However, clinical practice and guidelines differ in their recommendations. We evaluate real-world utilization and practice patterns of IADT. MATERIALS AND METHODS: Ontario men ≥65 years of age with PC who initiated ADT for ≥3 months were identified (1997-2017). Lapses in ADT ≥6 months (initial gap) and ≥3 months (subsequent gaps) were used to classify IADT. Neoadjuvant/adjuvant therapy was excluded. Disease stage adjustment was completed for patients with likely metastatic disease based on de novo presentation with ADT. Patient and physician predictors of IADT were analyzed using multivariable logistic regression. RESULTS: We identified 8,544 patients with 1,715 having previously received local therapy. Among all patients, 16.4% received IADT. This ranged from 11.4%-24.8% across health-planning regions and increased to 26.6% in those with previous local therapy. Mean followup was 8.3 years. Patients with prior local therapy (OR 1.85, 95% CI 1.59-2.17, p <0.001) and those in the highest income quintile (OR 1.32, 95% CI 1.08-1.60, p=0.005) had increased odds of receiving IADT. Radiation oncologists were more likely to use IADT than urologists (OR 1.99, 95% CI 1.59-2.50, p <0.001), as were physicians with more experience (≥10 years in practice: OR 1.44, 95% CI 1.11-1.88, p=0.007). In specialty-stratified analyses, case volume was significantly associated with IADT for radiation oncologists (highest quartile: OR 1.73, 95% CI 1.14-2.62, p=0.009). CONCLUSIONS: IADT remains underutilized for patients with PC who ≥65 years of age with only 1 in 4 to 1 in 6 eligible patients receiving this form of care. Clinical, sociodemographic and physician characteristics play an important role in treatment selection.

Estimating the costs of intensity-modulated and 3-dimensional conformal radiotherapy in Ontario.

BACKGROUND: Radiotherapy is a common treatment for many cancers, but up-to-date estimates of the costs of radiotherapy are lacking. In the present study, we estimated the unit costs of intensity-modulated radiotherapy (imrt) and 3-dimensional conformal radiotherapy (3D-crt) in Ontario. METHODS: An activity-based costing model was developed to estimate the costs of imrt and 3D-crt in prostate cancer. It included the costs of equipment, staff, and supporting infrastructure. The framework was subsequently adapted to estimate the costs of radiotherapy in breast cancer and head-and-neck cancer. We also tested various scenarios by varying the program maturity and the use of volumetric modulated arc therapy (vmat) alongside imrt. RESULTS: From the perspective of the health care system, treating prostate cancer with imrt and 3D-crt respectively cost $12,834 and $12,453 per patient. The cost of radiotherapy ranged from $5,270 to $14,155 and was sensitive to analytic perspective, radiation technique, and disease site. Cases of head-and-neck cancer were the most costly, being driven by treatment complexity and fractions per treatment. Although imrt was more costly than 3D-crt, its cost will likely decline over time as programs mature and vmat is incorporated. CONCLUSIONS: Our costing model can be modified to estimate the costs of 3D-crt and imrt for various disease sites and settings. The results demonstrate the important role of capital costs in studies of radiotherapy cost from a health system perspective, which our model can accommodate. In addition, our study established the need for future analyses of imrt cost to consider how vmat affects time consumption.

Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D.

SUMMARY: Androgen deprivation therapy in 80 men was associated with declines in bone mineral density (BMD), which were greatest in the first year, and in the lumbar spine compared to controls. Vitamin D use was associated with improved BMD in the lumbar spine and in the first year. INTRODUCTION: Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased risk of fractures. Although loss of BMD appears to be greatest within the first year of starting ADT, there are few long-term studies of change in BMD, and risk factors for bone loss are not well-characterized. METHODS: Men aged 50+ with nonmetastatic prostate cancer starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Matched controls were men with prostate cancer not receiving ADT. Multivariable regression analysis examined predictors of BMD loss. RESULTS: Eighty ADT users and 80 controls were enrolled (mean age 69 years); 52.5 % had osteopenia and 8.1 % had osteoporosis at baseline. After 1 year, in adjusted models, ADT was associated with significant losses in lumbar spine BMD compared to controls (-2.57 %, p = 0.006), with a trend towards greater declines at the total hip (p = 0.09). BMD changes in years 2 and 3 were much smaller and not statistically different from controls. Use of vitamin D but not calcium was associated with improved BMD in the lumbar spine in year 1 (+6.19 %, p < 0.001) with smaller nonsignificant increases at other sites (+0.86 % femoral neck, +0.86 % total hip, p > 0.10) primarily in the first year. CONCLUSIONS: Loss of BMD associated with ADT is greatest at the lumbar spine and in the first year. Vitamin D but not calcium may be protective particularly in the first year of ADT use.

The importance of local control in high-risk locally advanced prostate cancer.

Prostate cancer is a common malignancy worldwide, and in Canada, it is the most frequently diagnosed cancer in men. The stratification of prostate cancer into risk categories has allowed for improved counselling of patients and provides guidance for treatment selection. However, the exact definition of high-risk prostate cancer remains controversial, and that lack of consensus remains a barrier to assessing available data from various institutions and from clinical trials. The proportion of patients with locally advanced high-risk disease has fallen in the last 20 years largely because of screening for prostate-specific antigen, but management in this population continues to be an important clinical problem. A factor that has emerged in recent years is the importance of local disease control, with data from multiple randomized trials suggesting that local therapy improves progression-free survival, disease-free survival, and overall survival. Further research in this population is necessary to improve outcomes.

Robotic retroperitoneal lymph node dissection for primary and post-chemotherapy testis cancer.

The role of retroperitoneal lymph node dissection (RPLND) in testicular cancer is well established in both the primary and post-chemotherapy setting. The aim of this study was to report our 2 years oncological outcomes of robotic RPLND. A retrospective review was performed of all patients undergoing robotic RPLND by a single surgeon at Princess Margaret Cancer Centre. Demographic, perioperative, and oncologic data were analyzed using descriptive statistics. Between September 2014 and June 2020, 141 patients underwent an RPLND [33 (23.4%) were primary, 108 (76.6%) were post-chemotherapy]. 27 (19.1%) patients underwent a robotic bilateral template nerve-sparing RPLND. RPLND indication was primary (i.e. pre-chemotherapy) in 18 (66.7%), and post-chemotherapy in 9 (33.3%) patients. Stage at RPLND was 2A (n = 15, 55.6%), 2B (n = 9, 33.3%), 2C (n = 1, 3.7%) and 3 (n = 2, 7.4%). Median OR time (incision to closure) was 525 min and blood loss was 200 ml. Nerve sparing was performed in all but one case. Six (22.2%) adjuvant procedures were performed including two (7.4%) vascular repairs. Median length of stay was 2 days. Viable tumor was detected in 17 (63%) and teratoma in 9 (33.3%). Median follow-up was 31.3 months. No adjuvant chemotherapy was given. Three patients (11.1%) relapsed: 2 out-of-field and 1 with both in-field and out-of-field disease. Robotic RPLND can be performed safely. Long-term follow-up of series such as ours, enriched with patients with viable disease and/or teratoma, and not treated with adjuvant chemotherapy is required to ensure oncological outcomes are comparable to the open approach.

Organisational standards for the delivery of intensity-modulated radiation therapy in Ontario.

By minimising the effect of irradiation on surrounding tissue, intensity-modulated radiation therapy (IMRT) can deliver higher, more effective doses to the targeted tumour site, minimising treatment-related morbidity and possibly improving cancer control and cure. A multidisciplinary IMRT Expert Panel was convened to develop the organisational standards for the delivery of IMRT. The systematic literature search used MEDLINE, EMBASE, the Cochrane Database, the National Guidelines Clearing House and the Health Technology Assessment Database. An environmental scan of unpublished literature used the Google search engine to review the websites of key organisations, cancer agencies/centres and vendor sites in Canada, the USA, Australia and Europe. In total, 22 relevant guidance documents were identified; 12 from the published literature and 10 from the environmental scan. Professional and organisational standards for the provision of IMRT were developed through the analysis of this evidence and the consensus opinion of the IMRT Expert Panel. The resulting standards address the following domains: planning of new IMRT programmes, practice setting requirements, tools, devices and equipment requirements; professional training requirements; role of personnel; and requirements for quality assurance and safety. Here the IMRT Expert Panel offers organisational and professional standards for the delivery of IMRT, with the intent of promoting innovation, improving access and enhancing patient care.

Defining advanced practice in radiation therapy: A feasibility assessment of a new healthcare provider role in Ontario, Canada.

INTRODUCTION: This study assesses the feasibility of a new role for radiation therapists in Ontario, Canada, called the Advanced Practice Radiation Therapist (APRT), which would address health service pressures and improve patients' access to care. METHODS: A literature search and expert consensus were used to define advanced practice. A standardized template was used to record each APRTs activities/competencies, along with the requisite knowledge, skills and judgment required to perform these competencies. A thematic analysis of the lists was undertaken to develop a single competency profile. Seven APRTs were deployed at four cancer centres to gather contextual information on the development and integration of the new role. RESULTS: The definition of AP consists of seven key traits and includes a framework identifying stages of practice from entry-level practitioner through expert to advanced practitioner. The competency profile consists of clinical, technical and professional domains which further define the scope of practice and shepherd the role through stages of implementation. Role testing showed support for the role and demonstrated that APRTs can deliver specialized services, perform delegated tasks and their work can lead to program efficiencies and new services. The new role may also lead to improved radiation therapist recruitment rates and work satisfaction. CONCLUSIONS: This feasibility assessment served as the foundation for the future long-term implementation of the Clinical Specialist Radiation Therapist (CSRT) Project. As of 2018, there were 24 CSRTs in Ontario. The APRT role is a natural progression for a readying profession which can play a transformative role in addressing health human resource shortages.

A comprehensive systematic review of testicular germ cell tumor surveillance.

BACKGROUND: Testicular cancer is the most common malignancy in men aged 15-34, and its incidence has been increasing over the past half-century. Survival for stage I testis cancer approaches 100% regardless of management strategy which is often dictated by other factors such as perceived morbidity. Advances in treatment have attempted to decrease morbidity and surveillance is thought to achieve this goal. METHODS: An English language literature search of MEDLINE from 1966 to December 2005 and CINAHL from 1982 to December 2005 was conducted using a broad search strategy. Comparative and descriptive original articles on outcomes of seminoma or NSGCT surveillance would be deemed eligible and review articles containing no original data were omitted. One hundred and thirty-eight articles were selected for formal review, during which a database was compiled that documented the first author, publication year, tumor histologic type, study purpose or topic(s), methodology, sample size, median follow-up, and relevant results. RESULTS: Most evidence for the efficacy of surveillance is from descriptive series or non-experimental comparative studies. Relapse occurs in approximately 28% and 17% of surveillance patients in NSGCT and seminoma, respectively, and cause-specific survival is approximately 98% and 100%, respectively. Compliance with surveillance ranges from poor to adequate, however there is no evidence that compliance impacts clinical outcome. Cost analyses have yielded inconsistent results when comparing treatment modalities. There is scant literature on quality of life and psychosocial issues and results are inconsistent. Active surveillance appears to be appropriate and perhaps optimal first line management of clinical stage I seminoma and non-seminomatous germ cell tumors. Further quantitative and qualitative research is warranted to deepen understanding of these issues that may impact treatment decision-making.

Best Practice Recommendations for the Retention of Radiotherapy Records.

This paper offers best practice recommendations for the maintenance and retention of radiotherapy health records and technical information for cancer programmes. The recommendations are based on a review of the published and grey literature, feedback from key informants from seven countries and expert consensus. Ideally, complete health records should be retained for 5 years beyond the patient's lifetime, regardless of where they are created and maintained. Technical information constituting the radiotherapy plan should also be retained beyond the patient's lifetime for 5 years, including the primary images, contours of delineated targets and critical organs, dose distributions and other radiotherapy plan objects. There have been increased data storage and access requirements to support modern image-guided radiotherapy. Therefore, the proposed recommendations represent an ideal state of radiotherapy record retention to facilitate ongoing safe and effective care for patients as well as meaningful and informed retrospective research and policy development.

Explaining socioeconomic status effects in laryngeal cancer.

INTRODUCTION: People with lower socioeconomic status (SES) experience shorter survival times after a cancer diagnosis for many disease sites. We determined whether area-level SES was associated with the outcomes: cause-specific survival and local-regional failure in laryngeal cancer in Ontario, Canada. When we found an association we sought explanations that might be related to access to care including age, sex, rural residence, tumor stage, lymph node status, use of diagnostic imaging, treatment type, percentage of prescribed radiotherapy delivered, number of radiotherapy interruption days, treatment waiting time, and treating cancer center. MATERIALS AND METHODS: The study population consisted of 661 glottic and 495 supraglottic stage-stratified randomly-sampled patients identified using the Ontario Cancer Registry. Area-level SES quintiles were assigned using adjusted median household income from the Canadian Census. Other data were collected from patient charts. Explanations for SES effects were determined by measuring whether the effect moved toward the null value by at least 10% when an access indicator was added to a the model. RESULTS: Socioeconomic status was not related to either outcome for those with supraglottic cancer, but an association was present in glottic cancer. With the highest socioeconomic status quintile as the referent group, the relative risks for patients in the lowest socioeconomic quintile were 2.75 (95% CI 1.48, 5.12) for cause-specific survival and 1.90 (95% CI 1.24, 2.93) for local-regional failure. Disease stage as measured by T-category explained between 3% and 23% of these socioeconomic effects. None of the other access indicators met our 10% change criterion. CONCLUSION: We question why people in lower socioeconomic quintiles were not diagnosed earlier in the disease progression. Having ruled out several variables that may be related to access to care, additional biologic and social variables should be examined to further understand socioeconomic status effects.

Clinical Characteristics and Outcomes of Late Relapse in Stage I Testicular Seminoma.

AIMS: To identify the characteristics and outcomes associated with late relapse in stage I seminoma. MATERIALS AND METHODS: A retrospective review was carried out of all patients with stage I seminoma managed at our institution between 1981 and 2011. Data were obtained from a prospectively maintained database. Late relapse was defined as tumour recurrence > 2 years after orchiectomy. RESULTS: Overall, 1060 stage I seminoma patients were managed with active surveillance (n=766) or adjuvant radiotherapy (n=294). At a median follow-up of 10.6 years (range 1.2-30), 142 patients relapsed at a median (range) of 14 (3-129) months; 128 on active surveillance and 14 after adjuvant radiotherapy. The late relapse rate for the active surveillance and adjuvant radiotherapy groups was 4% and 1%, respectively. There was no specific clinicopathological factor associated with late relapse. Isolated para-aortic node(s) was the most common relapse site in active surveillance patients either in late (88%) or early relapse (82%). Among the active surveillance group, no patients with late relapse subsequently developed a second relapse after either salvage radiotherapy (n=25) or chemotherapy (n=6), whereas in early relapse patients a second relapse was reported in seven (10%) of 72 patients treated with salvage radiotherapy and one (4%) of 23 patients who received chemotherapy; all second relapses were subsequently salvaged with chemotherapy. No patient in the adjuvant radiotherapy group developed a second relapse after salvage chemotherapy (n=10) or inguinal radiotherapy/surgery (n=4). Of seven deaths, only one was related to seminoma. Among active surveillance patients, the 10 year overall survival for late and early relapse groups were 100% and 96% (P = 0.2), whereas the 10 year cancer-specific survival rates were 100% and 99% (P = 0.3), respectively. CONCLUSIONS: In stage I seminoma, the extent and pattern of late relapse is similar to that for early relapse. For active surveillance patients, selective use of salvage radiotherapy/chemotherapy for relapse results in excellent outcomes regardless of the timing of relapse, whereas salvage radiotherapy for late relapse seems to be associated with a minimal risk of second relapse.

Omission of Breast Radiotherapy in Low-risk Luminal A Breast Cancer: Impact on Health Care Costs.

AIMS: The economic burden of cancer care is substantial, including steep increases in costs for breast cancer management. There is mounting evidence that women age ≥ 60 years with grade I/II T1N0 luminal A (ER/PR+, HER2- and Ki67 ≤ 13%) breast cancer have such low local recurrence rates that adjuvant breast radiotherapy might offer limited value. We aimed to determine the total savings to a publicly funded health care system should omission of radiotherapy become standard of care for these patients. MATERIALS AND METHODS: The number of women aged ≥ 60 years who received adjuvant radiotherapy for T1N0 ER+ HER2- breast cancer in Ontario was obtained from the provincial cancer agency. The cost of adjuvant breast radiotherapy was estimated through activity-based costing from a public payer perspective. The total saving was calculated by multiplying the estimated number of luminal A cases that received radiotherapy by the cost of radiotherapy minus Ki-67 testing. RESULTS: In 2010, 748 women age ≥ 60 years underwent surgery for pT1N0 ER+ HER2- breast cancer; 539 (72%) underwent adjuvant radiotherapy, of whom 329 were estimated to be grade I/II luminal A subtype. The cost of adjuvant breast radiotherapy per case was estimated at $6135.85; the cost of Ki-67 at $114.71. This translated into an annual saving of about $2.0million if radiotherapy was omitted for all low-risk luminal A breast cancer patients in Ontario and $5.1million across Canada. CONCLUSION: There will be significant savings to the health care system should omission of radiotherapy become standard practice for women with low-risk luminal A breast cancer.

Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis.

PURPOSE: Our main purpose was to determine whether the addition of thoracic radiation therapy to systemic chemotherapy improves 2-year survival, improves local (intrathoracic) tumor control, and affects treatment-related mortality in patients with limited-stage small-cell carcinoma of the lung. DESIGN: Eleven randomized trials addressing this issue were identified using a computerized literature search (Medline and Cancerline) and by polling senior investigators in the field. A meta-analysis was then performed and the results of the trials were analyzed in two ways, the odds ratio (OR) (Peto) method and the risk difference method (Dersimonian and Laird). RESULTS: The overall OR for benefit of thoracic radiation on 2-year survival (ie, the odds of surviving 2 years among patients allocated to radiation compared with the odds of surviving 2 years among patients allocated to control) is 1.53 (95% confidence interval [CI], 1.30 to 1.76; chi 2 = 12.76; P less than .001). The risk difference method showed that radiation therapy improved 2-year survival by 5.4% (95% CI, 1.1% to 9.7%). Local control results were available for only nine studies, the OR for treatment benefit is 3.02 (95% CI, 2.80 to 3.24; chi 2 = 101.48; P less than .0001), and intrathoracic tumor control was improved by 25.3% (95% CI, 16.5% to 34.1%). The OR for excess treatment-related deaths in the thoracic radiation-treated patients was 2.54 (95% CI, 1.90 to 3.18; chi 2 = 8.24; P less than .01). The risk difference for treatment-related deaths was 1.2% (95% CI, -0.6% to 3.0%). CONCLUSIONS: This meta-analysis shows a small but significant improvement in survival and a major improvement in tumor control in the thorax in patients receiving thoracic radiation therapy. However, this is achieved at the cost of a small increase in treatment-related mortality.

Resource implications of palliative chemotherapy for ovarian cancer.

PURPOSE: To describe the costs and outcomes of palliative chemotherapy in women with recurrent and refractory ovarian cancer from the perspective of a health care provider. PATIENTS AND METHODS: A retrospective study of 40 consecutive women who started second- or third-line chemotherapy for recurrent or refractory ovarian cancer between 1989 and 1992. Resource utilization from the commencement of second- or third-line chemotherapy until death or last follow-up evaluation was determined from a detailed chart review. All elements of care were recorded, including inpatient admissions, outpatient visits, chemotherapy drugs, nonchemotherapy drugs, radiation therapy, surgical procedures, investigations, and home care. Costs calculated using the hotel-approximation method are expressed in 1994 Canadian dollars. Actuarial estimates of cost and survival were used to account for censored observations. RESULTS: After a minimum follow-up period of 24 months, 36 of 40 women had died. The median survival duration of the group was 1.1 years from study entry and 1.7 years from first relapse. The women received a median of two regimens of chemotherapy (range, one to four) from study entry. They spent a median of 33 days as hospital inpatients (mean, 46; range, 0 to 185); 58% of these inpatient days were for symptomatic management and 32% were for chemotherapy. The mean cost per patient was $53,000 (median, $36,600; range, $4,800 to $162,900). The relationship between cost and survival duration was not linear--the cost per year was lowest for those who lived longest. Inpatient admissions, chemotherapy drugs, and outpatient visits accounted for 62%, 21%, and 8% of the total cost, respectively. The total costs attributable to chemotherapy were $24,000 (45% of total costs) and the total costs attributable to supportive care were $23,000 (43% of total costs). CONCLUSION: These data illustrate the cost of palliative management of recurrent and refractory ovarian cancer, which must be considered in the context of quality and duration of survival. They indicate the potential to improve cost efficiency by improving resource management, for example, by shifting from inpatient to outpatient chemotherapy, everything else being equal.

Counting the costs of chemotherapy in a National Cancer Institute of Canada randomized trial in nonsmall-cell lung cancer.

An economic evaluation was undertaken of a previously reported National Cancer Institute of Canada (NCIC) trial of chemotherapy in advanced nonsmall-cell lung cancer (NSCLC). That trial had demonstrated a survival benefit associated with the use of either vindesine and cisplatin (VP) or cyclosphosphamide, doxorubicin, and cisplatin (CAP) in relation to best supportive care (BSC). The economic technique used in this evaluation was cost-effectiveness analysis (CEA). All costs were determined from the viewpoint of two provincial health care plans. When compared with BSC, the survival benefit of 8 weeks in favor of patients receiving CAP chemotherapy was associated with an economic saving of $949.49 (in 1984 Canadian dollars). This translated into a savings of $6,171.69 per year of life gained. The mean survival benefit of 12.8 weeks that was obtained with VP chemotherapy compared with BSC was associated with an increased cost of $3,637.60 per patient, or $14,777.75 per year of life gained. The economic evaluation demonstrated that the majority of costs on each of the three treatment arms was related to hospitalization and not to the use of chemotherapy agents. These results compare favorably with estimates of cost-effectiveness (CE) of commonly used treatments for other diseases and demonstrate that a policy of supportive care is associated with costs that may exceed those of active treatment. It is concluded that economic factors should not adversely affect decisions regarding the use of chemotherapy in advanced NSCLC.

Management of stage II seminoma.

PURPOSE: To assess the results of treatment, patterns of failure, and prognostic factors for relapse in a contemporary cohort of patients with stage II seminoma. MATERIALS AND METHODS: From January 1981 and December 1993, 99 patients (median age, 35 years) with stage II seminoma (IIA, 41; IIB, 28; IIC, 24; IID, six) were managed at our institution. Eighty were treated with radiation therapy (RT) and 19 with chemotherapy (ChT). RESULTS: With a median follow-up of 6.7 years, the five-year overall actuarial survival was 94%, the 5-year cause-specific survival was 94%, and the 5-year relapse-free rate was 83%. Sixteen (20%) of the 80 patients treated with RT relapsed (median time to relapse, 9 months). Relapse occurred outside the irradiated area in all but two patients. Distant relapse sites included the supraclavicular fossa, bone (four patients, three with spinal cord compression), and lung/mediastinum. All 19 patients treated primarily with ChT achieved disease control and none has relapsed. The relapse rate at 5 years for patients with stage IIA to IIB was 11% (seven of 64), and 56% (nine of 16) for those with stage IIC to IID disease (P < .0001). No patient with IIC or IID disease treated with ChT relapsed as compared with 56% of patients treated with RT (0 of 14 v nine of 16, P = .002). CONCLUSION: Radiation therapy is highly effective in patients with stage IIA or IIB seminoma (89% were relapse free). In stage IIC or IID disease, although local control with RT is excellent, a 50% risk of distant relapse is unacceptable, and not all patients who relapse can be salvaged. Chemotherapy should clearly be the primary treatment in patients with stage IIC or IID seminoma.

Stage I testicular seminoma: results of adjuvant irradiation and surveillance.

PURPOSE: To assess the results of treatment and patterns of relapse in a contemporary group of patients with stage I testicular seminoma managed by adjuvant radiation therapy (RT) and surveillance. PATIENTS AND METHODS: Between January 1981 and December 1991, 364 patients with stage I seminoma were treated at Princess Margaret Hospital. Of these, 194 were treated with adjuvant RT (92% received a dose of 25 Gy in 20 fractions for 4 weeks) and 172 were managed by surveillance. Two patients were included in this series twice--both had postorchiectomy RT for stage I disease, developed a contralateral seminoma, and were placed on surveillance and analyzed for outcome of both primary tumors. The median follow-up period for patients treated with adjuvant RT was 8.1 years (range, 0.2 to 12), and for patients managed by surveillance, it was 4.2 years (range, 0.6 to 10.1). RESULTS: The overall 5-year actuarial survival rate for all patients was 97%, and the cause-specific survival rate was 99.7%. Only one patient died of seminoma. Of 194 patients treated with RT, 11 have relapsed, with a 5-year relapse-free rate of 94.5%. Prognostic factors for relapse included histology, tunica invasion, spermatic cord involvement, and epididymal involvement. Twenty-seven patients developed disease progression on surveillance, which resulted in a 5-year progression-free rate of 81.9%. The only factor identified to predict progression on surveillance was age at diagnosis: patients aged < or = 34 years had a 26% risk of progression at 5 years, in contrast to a 10% risk of progression in those greater than 34 years of age. CONCLUSION: The outcome of patients with stage I testicular seminoma is excellent, with only one of 364 patients (0.27%) dying of disease. In our experience, both a policy of adjuvant RT and of surveillance resulted in a high probability of cure. Our surveillance experience showed that four of five patients with stage I seminoma are cured with orchiectomy alone. The benefit of adjuvant RT was reflected in a decreased relapse rate. We have identified a number of prognostic factors for relapse in patients managed with both approaches, but further study of prognostic factors is required, particularly to identify patients at high risk of disease progression on surveillance.

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Intra-prostatic fiducial markers and concurrent androgen deprivation.

AIMS: To document the case of a man with adenocarcinoma of the prostate treated with external beam radiotherapy and concurrent androgen deprivation. MATERIALS AND METHODS: The man, who received 79.8 Gy in 42 fractions of radiotherapy over 8.5 weeks using three intra-prostatic gold fiducial markers for on-line set-up correction, started an anti-androgen 2.5 weeks before radiotherapy, on the day of his planning computed tomography, and a gonadotropin-releasing hormone agonist on his first day of radiotherapy. RESULTS: In the sixth week of radiotherapy, the distance between the fiducial markers had diminished: superior to posterior-mid (from 19 to 11 mm), posterior-mid to inferior (from 19 to 15 mm), and superior to inferior (from 31 to 22 mm), so the patient was rescanned. Between the two planning computed tomographies, the prostate volume had decreased from 44.3 to 28.3 cm3 (-36%). Had the planned radiotherapy been delivered to the anatomy of the rescan, the dose to the rectal wall would have exceeded the planned dose-volume histogram constraints. However, with the patient set up to the fiducial markers, the dose-volume histogram constraints for the rectal wall and bladder wall were met throughout the course of radiotherapy. CONCLUSION: Involution of the prostate owing to concurrent androgen deprivation may cause in-migration of implanted fiducial markers and excessive dose to the rectal wall. With concurrent androgen deprivation, daily on-line set-up correction to fiducial markers can aid in safe dose escalation.

Radiation therapy for high-risk prostate cancer--a review.

The term high-risk prostate cancer has been coined to encompass a group of patients with a poor prognosis (clinical stage T3/T4, or T1/T2 with PSA > 20 ng/ml or GS > 8). It is estimated that 20% of patients in Canada present with high-risk disease, which translates into approximately 4000 new cases each year. The optimal management approach is unclear but the standard of care in North America for this group of patients is radiation therapy (RT) with prolonged adjuvant hormonal therapy. Current clinical trials are evaluating the role of local therapy, the value of RT dose escalation, the potential benefit of regional lymph node irradiation, the appropriate duration of adjuvant hormonal therapy, as well as the possible impact of adjunctive chemotherapy. The high-risk group of patients contains a wide spectrum of disease, ranging from patients with aggressive localized disease to those with widespread occult distant metastases. The current challenge facing clinicians is appropriate treatment selection for individual patients. Information from novel biomarkers and improved imaging, as well as more effective local and adjunctive systemic therapies is necessary to improve outcomes for men with this aggressive disease.