PMH 9907: Long-term outcomes of a randomized phase 3 study of short-term bicalutamide hormone therapy and dose-escalated external-beam radiation therapy for localized prostate cancer.

BACKGROUND: The role of hormone therapy (HT) with dose-escalated external-beam radiotherapy (DE-EBRT) in the treatment of intermediate-risk prostate cancer (IRPC) remains controversial. The authors report the long-term outcome of a phase 3 study of DE-EBRT with or without HT for patients with localized prostate cancer (LPC). METHODS: From 1999 to 2006, 252 of an intended 338 patients with LPC were randomized to receive DE-EBRT with or without 5 months of neoadjuvant and concurrent bicalutamide 150 mg once daily. The study was closed early because of contemporary concerns surrounding bicalutamide. The primary outcome was biochemical failure (BF) incidence, and the secondary endpoints were overall survival (OS), local control (LC), and quality of life. The BF and OS rates were estimated using the cumulative incidence function and Kaplan-Meier methods and were compared using the Gray test and the log-rank test. RESULTS: Eleven patients were excluded from analysis. Characteristics were well balanced in each treatment arm. Ninety-five percent of patients had IRPC. The prescribed dose increased from 75.6 grays (Gy) in 42 fractions to 78 Gy in 39 fractions over the period. At a median follow-up of 9.1 years, 98 BFs occurred, with no significant effect of HT versus no HT on the BF rate (40% vs 47%; P = .32), the OS rate (82% vs 86%; P = .37), the LC rate (52% vs 48 %; P = .32) or quality of life, in the patients who completed the questionnaires. Dose escalation to 75.6 Gy versus >75.6 Gy reduced the BF rate by 26% (P = .004). CONCLUSIONS: For patients who predominantly have IRPC, the addition of HT to DE-EBRT did not significantly affect BF, OS, or LC. Bicalutamide appeared to be well tolerated. The conclusions from the study are limited by incomplete recruitment. Cancer 2016;122:2595-603. © 2016 American Cancer Society.

Clinicopathologic factors that influence prognosis and survival outcomes in men with metastatic castration-resistant prostate cancer treated with Radium-223.

BACKGROUND: In men with metastatic castration-resistant prostate cancer (mCRPC) with primarily bone metastases, radium-223 (223 Ra) improves overall survival (OS). However, the selection of 223 Ra is not guided by specific validated clinicopathologic factors, and thus outcomes are heterogeneous. PATIENTS AND METHODS: This retrospective survival analysis was performed in men with mCRPC treated with 223 Ra at our cancer center. Demographics and disease characteristics were collected. OS was calculated using the Kaplan-Meier method (log-rank). The potential prognostic factors were determined using both univariable (UVA) and multivariable analysis (MVA) (Cox-regression) methods. RESULTS: In total, 150 patients with a median age of 74 years (52-93) received 223 Ra between May 2015 and July 2018, and 58% had 6-20 bone metastases. Ninety-four (63%) patients received >4 223 Ra doses, and 56 (37%) received ≤4. The following pre-treatment factors were analyzed (median [range]): eastern cooperative oncology group performance status (ECOG PS), (1 [0-3]); Albumin (ALB), (39 g/L [24-47]); alkaline phosphatase (ALP), (110 U/L [35-1633]); and prostate-specific antigen (PSA), (49 µg/L [0.83-7238]). The median OS for all patients was 14.5 months (95% CI: 11.2-18). These factors were associated with poor survival outcomes in UVA and MVA: ALB <35 g/L, ALP >150 U/L, ECOG PS 2-3, and PSA >80 µg/L. By assigning one point for each of these factors, a prognostic model was developed, wherein three distinct risk groups were identified: good, 0-1 (n = 103); intermediate, 2 (n = 30); and poor risk, 3-4 points (n = 17). The median OS was 19.4, 10.0, and 3.1 months, respectively (p < 0.001). CONCLUSIONS: Pre-treatment ALB, ALP, ECOG, and PSA, were significantly correlated with OS and could guide treatment selection for men with mCRPC by identifying those who are most or least likely to benefit from 223 Ra. Validation in an independent dataset is required prior to widespread clinical utilization.

Current topics in radiotherapy for genitourinary cancers: Consensus statements of the Genitourinary Radiation Oncologists of Canada.

INTRODUCTION: The biennial meeting of the Genitourinary Radiation Oncologists of Canada (GUROC) took place November 22-23, 2019. A consensus-building session was held during the meeting addressing topics of emerging interest or controversy in the management of genitourinary malignancies. METHODS: Draft statements were debated among all meeting attendees in an open forum with anonymous live voting. Statements for which there was at least 75% agreement among attendees were adopted as GUROC consensus. RESULTS: Four evidence-based consensus statements were developed. First, the use of prostate radiotherapy is recommended in the setting of de novo low-volume metastatic hormone-sensitive prostate cancer to improve overall survival. Second, the support of ongoing randomized trials evaluating metastasis-directed ablative local therapy in oligometastatic prostate cancer is recommended; where such trials are available, off-trial use of oligometastasis-directed ablative radiotherapy at this time is strongly discouraged. Third, routine use of prostate-rectal hydrogel spacer devices in patients with localized prostate cancer planned to receive external beam radiotherapy is not recommended; instead, selective use in patients at highest risk of rectal toxicity may be considered. Finally, multidisciplinary consultation is recommended for all patients with newly diagnosed localized muscle-invasive bladder cancer. CONCLUSIONS: The GUROC consensus statements provide practical guidance to clinicians in areas of current controversy in the management of prostate and bladder cancer, and it is hoped that their implementation will contribute to improved outcomes in real-world practice and greater support of clinical trials.

Accuracy and sensitivity of finite element model-based deformable registration of the prostate.

PURPOSE: Evaluate the accuracy and the sensitivity to contour variation and model size of a finite element model-based deformable registration algorithm for the prostate. METHODS AND MATERIALS: Two magnetic resonance images (MRIs) were obtained for 21 prostate patients with three implanted markers. A single observer contoured the prostate and markers and performed blinded recontouring of the first MRI. A biomechanical-model based deformable registration algorithm, MORFEUS, was applied to each dataset pair, deforming the second image (B) to the first image (A). The residual error was calculated by comparing the center of mass (COM) of the markers with the predicted COM. Sensitivity to contour variation was calculated by deforming B to the repeat contour of A (A2). The sensitivity to the model size was calculated by reducing the number of nodes (B', A', A2') and repeating the analysis. RESULTS: The average residual error of the registration for B to A and B to A2 was 0.22 cm (SD: 0.08 cm) and 0.24 cm (SD: 0.09 cm), respectively. The average residual error of the registration of B' to A' and B' to A2' was 0.22 cm (SD: 0.10 cm) and 0.25 cm (SD: 0.10 cm), respectively. The average time to run MORFEUS on the standard and reduced model was 3606 s (SD: 7788 s) and 56 s (SD: 16 s), respectively. CONCLUSIONS: The accuracy of the algorithm, equal to the image voxel size, is not affected by intraobserver contour variability or model size. Reducing the model size significantly increases algorithm efficiency.

A magnetic resonance imaging study of prostate deformation relative to implanted gold fiducial markers.

PURPOSE: To describe prostate deformation during radiotherapy and determine the margins required to account for prostate deformation after setup to intraprostatic fiducial markers (FM). METHODS AND MATERIALS: Twenty-five patients with T1c-T2c prostate cancer had three gold FMs implanted. The patients presented with a full bladder and empty rectum for two axial magnetic resonance imaging (MRI) scans using a gradient recalled echo (GRE) sequence capable of imaging the FMs. The MRIs were done at the time of radiotherapy (RT) planning and a randomly assigned fraction. A single observer contoured the prostate surfaces. They were entered into a finite element model and aligned using the centroid of the three FMs. RESULTS: During RT, the prostate volume decreased by 0.5%/fraction (p = 0.03) and the FMs in-migrated by 0.05 mm/fraction (p < 0.05). Prostate deformation was unrelated to differential bladder and bowel filling, but was related to a transurethral resection of the prostate (TURP) (p = 0.003). The standard deviation for systematic uncertainty of prostate surface contouring was 0.8 mm and for FM centroid localization was 0.4 mm. The standard deviation of random interfraction prostate deformation was 1.5 mm and for FM centroid variability was 1.1 mm. These uncertainties from prostate deformation can be incorporated into a margin recipe to determine the total margins required for RT. CONCLUSIONS: During RT, the prostate exhibited: volume decrease, deformation, and in-migration of FMs. Patients with TURPs were prone to prostate deformation.

Long-term outcome of radiation-based conservation therapy for invasive bladder cancer.

PURPOSE: To report the long-term results and examine factors associated with bladder preservation, risk of relapse, and survival in patients treated with radical radiotherapy for invasive bladder cancer. MATERIALS AND METHODS: Between 1986 and 1997, 340 patients with T1-T4 bladder cancer were treated at Princess Margaret Hospital and received radiotherapy alone, radiotherapy and concurrent cisplatin chemotherapy, or neoadjuvant chemotherapy followed by radiotherapy. Patients having complete response were followed with regular cystoscopy. Cystectomy was undertaken in suitable patients with persistent or locally recurrent disease. RESULTS: The median age of patients was 71 years, 13% had evidence of regional lymph node involvement, and 27% were medically unfit for radical cystectomy. A total of 247 patients received radiotherapy alone, 36 radiotherapy and concurrent cisplatin chemotherapy, and 57 neoadjuvant chemotherapy followed by radiotherapy. Complete response was obtained in 63.5% of patients overall, and median follow-up was 7.9 years. The 10-year overall survival, cause-specific survival, and local relapse-free rates were 19%, 35%, and 32%, respectively. In 131 patients with muscle-invasive disease confined to the bladder wall (T2N0M0), 10-year cause-specific survival (P = 0.02) and local relapse-free rates (P = 0.03) were 68% and 60% when carcinoma in situ was absent, and 47% and 28%, respectively, when present. In multivariable analysis, younger age, lower T category, and absence of carcinoma in situ were associated with a statistically significant improvement in survival and local control (P

Impact of Granulocyte-colony Stimulating Factor on Bleomycin-induced Pneumonitis in Chemotherapy-treated Germ Cell Tumors.

OBJECTIVE: To examine the impact of granulocyte-colony stimulating factor (G-CSF) use on the incidence and severity of bleomycin-induced pneumonitis (BIP) in patients with germ cell tumor (GCT) receiving first-line chemotherapy. PATIENTS AND METHODS: Clinical data from our institutional GCT database was complemented by review of radiology, pharmacy, and medical records. All patients receiving first line chemotherapy between January 1, 2000 and December 31, 2010 were included. Patients receiving at least 1 dose of G-CSF were identified. BIP was graded using Common Terminology Criteria for Adverse Events criteria. Logistic regression was used to explore predictors for risk and severity of BIP. Statistical significance was defined as P < .05. RESULTS: Data on 212 patients with GCT treated with a bleomycin-containing chemotherapy regimen were available. The median age was 31 years. The median follow-up period was 36.7 months. BIP occurred in 73 patients (34%), a majority (n = 55) of which were asymptomatic events (Common Terminology Criteria for Adverse Events, grade 1). G-CSF use was not associated with increased risk of BIP in multivariable analyses (odds ratio, 1.60; P = .13), nor was it associated with increased severity of symptomatic BIP (on average 1.22 grades higher; P = .09). There was a non-statistically significant trend towards greater risk of BIP in patients that developed renal impairment during chemotherapy treatment (odds ratio, 2.56; P = .053). CONCLUSION: In patients with GCT receiving first line chemotherapy, G-CSF use is not associated with an increased risk of BIP. Furthermore, the use of G-CSF did not have any significant effect on the severity of BIP events. Clinicians are reminded to be vigilant of patients that develop renal impairment while undergoing chemotherapy treatment, given the greater risk of BIP.

Compromised local control due to treatment interruptions and late treatment breaks in early glottic cancer: Population-based outcomes study supporting need for intensified treatment schedules.

PURPOSE: This population-based study describes the treatment of early glottic cancer in Ontario, Canada and assesses whether treatment variations were associated with treatment effectiveness. METHODS AND MATERIALS: We studied 491 T1N0 and 213 T2N0 patients. Data abstracted from charts included age, sex, stage, treatment details, disease control, and survival. RESULTS: The total dose ranged from 50 to 70 Gy, and the daily dose ranged from 1.9 to 2.8 Gy. In 90%, treatment duration was between 25 and 50 days. Field sizes, field reductions, beam arrangement, and beam energy varied. Late treatment breaks occurred in 13.6% of T1N0 and 27.1% of T2N0 cases. Local control was comparable to other reports for T1N0 (82% at 5 years), but was only 63.2% in T2N0. Variables associated with local failure in T1N0 were age less than 49 years (relative risk [RR], 3.21; 95% confidence interval [CI], 1.49-6.90) and >3 treatment interruption days (RR, 2.43; 95% CI, 1.00-5.91). In T2N0, these were field reduction (RR, 2.33; 95% CI, 1.23-4.42) and late treatment breaks (RR, 2.19; 95% CI, 1.09-4.41). CONCLUSION: Some aspects of treatment for early glottic cancer were associated with worse local control. Problems with protracted treatment are of particular concern, underscoring the need for randomized studies to intensify radiotherapy.

Testicular radiation for primary seminoma in a solitary testis.

Orchiectomy is the standard of care for patients with a second primary testicular tumor. We report a case of a man, with previous history of stage I left testicular germ cell tumor, who developed a contralateral seminoma and desired preservation of the remaining testis. Partial orchiectomy was not feasible due to tumor size and percutaneous needle biopsy revealed classical seminoma. He was treated with radiotherapy to the testis. Post treatment biopsy revealed no evidence of disease. At 32 months follow-up, he has not required androgen replacement. He has preservation of total testosterone level and libido.

Management and outcome differences in supraglottic cancer between Ontario, Canada, and the Surveillance, Epidemiology, and End Results areas of the United States.

PURPOSE: We compared the management and outcome of supraglottic cancer in Ontario, Canada, with that in the Surveillance, Epidemiology, and End Results (SEER) Program areas in the United States. METHODS: Electronic, clinical, and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Stage-stratified analyses compared initial treatment and survival in the SEER areas (n = 1,643) with a random sample from Ontario (n = 265). We also compared laryngectomy rates at 3 years in those patients 65 years and older at diagnosis. RESULTS: Radical surgery was more commonly used in SEER, with absolute differences increasing with increasing stage: I/II, 17%; III, 36%; and IV, 45%. The 5-year survival rates were 74% in Ontario and 56% in SEER for stage I/II disease (P =.01), 55.7% in Ontario and 46.8% in SEER for stage III disease (P =.40), and 28.5% in Ontario and 29.1% in SEER for stage IV disease (P =.28). Cancer-specific survival results mirrored the overall survival results with the exception of stage IV disease, for which 34.6% of Ontario patients survived their cancer compared with 38.1% in SEER (P =.10). This stage IV difference was more pronounced when we further controlled for possible cause of death errors by restricting the comparison to patients with a single primary cancer (P =.01). Three-year actuarial laryngectomy rates differed. In stage I/II, these rates were 3% in Ontario compared with 35% in SEER (P < 10(-3)). In stage III disease, the rates were 30% and 54%, respectively (P =.03), and in stage IV disease they were 33% and 64% (P =.002). CONCLUSION: There are large differences in the management of supraglottic cancer between the SEER areas of the United States and Ontario. Long-term larynx retention was higher in Ontario, where radiotherapy is widely regarded as the treatment of choice and surgery is reserved for salvage. In stages I to III, survival was similar in the two regions despite the differences in treatment policy. In stage IV, there may be a small survival advantage in the U.S. SEER areas related to the higher use of primary surgery.

Patterns of relapse in patients with clinical stage I testicular cancer managed with active surveillance.

PURPOSE: To evaluate the performance of active surveillance as a management strategy in broad populations and to inform the development of surveillance schedules by individual patient data regarding timing and type of relapse. METHODS: Retrospective study including data from 2,483 clinical stage I (CSI) patients, 1,139 CSI nonseminoma and 1,344 CSI seminoma managed with active surveillance, with the majority treated between 1998 and 2010. Clinical outcomes including relapse and death, time distribution, extent of relapse and method of relapse detection observed on active surveillance were recorded. RESULTS: Relapse occurred in 221 (19%) CSI-nonseminoma and 173 (13%) CSI-seminoma patients. Median time to relapse was 4 months (range, 2-61 months), 8 months (range, 2-77 months) and 14 months (range, 2-84 months) for lymphovascular invasion-positive CSI nonseminoma, lymphovascular invasion-negative CSI nonseminoma and CSI seminoma. Most relapses were observed within the first 2 years/3 years after orchiectomy for CSI nonseminoma (90%)/CSI seminoma (92%). Relapses were detected by computed tomography scan/tumor-markers in 87%/3% of seminoma recurrences, in 48%/38% of lymphovascular invasion-negative and 41%/61% of lymphovascular invasion-positive patients, respectively. 90% of CSI-nonseminoma and 99% of CSI-seminoma relapses exhibited International Germ Cell Collaborative Group good-risk features. Three patients with CSI nonseminoma died of disease (0.3%). One patient with CSI seminoma and two patients with CSI nonseminoma died because of treatment-related events. Overall, advanced disease was seen in both early- and late-relapse patients. All late recurrences were cured with standard therapy. Five-year disease-specific survival was 99.7% (95% CI, 99.24% to 99.93%). CONCLUSION: Active surveillance for CSI testis cancer leads to excellent outcomes. The vast majority of relapses occur within 2 years of orchiectomy for CSI nonseminoma and within 3 years for CSI seminoma. Late and advanced stage relapse are rarely seen. These data may inform further refinement of rationally designed surveillance schedules.

Large retroperitoneal lymphadenopathy as a predictor of venous thromboembolism in patients with disseminated germ cell tumors treated with chemotherapy.

PURPOSE: Cisplatin-based chemotherapy, a mainstay of treatment for disseminated germ cell tumors (GCTs), is associated with venous thromboembolism (VTE). Many patients with disseminated GCTs have large retroperitoneal lymph node (RPLN) metastases that may cause venous stasis and increase the risk of VTE development. We hypothesized that there was an association between large RPLN and chemotherapy-associated VTE risk. PATIENTS AND METHODS: The training cohort was composed of patients with disseminated GCT receiving first-line chemotherapy at Princess Margaret Cancer Centre between January 2000 and December 2010. Large RPLN was defined as more than 5 cm in maximal axial diameter. The predictive and discriminatory accuracies of a model using large RPLN in predicting VTE were compared with high-risk Khorana score (≥ 3) using logistic regression and area under receiver operator characteristic curves (AUROCs). The model was externally validated in a cohort of patients treated at the London Health Sciences Centre. RESULTS: The training cohort comprised 216 patients, 21 (10%) of whom developed VTE during chemotherapy. VTE was associated with large RPLN (odds ratio [OR], 5.26; P = .001), high-risk Khorana score (OR, 11.8; P < .001), intermediate-/poor-risk disease (OR, 3.76; P = .005), and hospitalization during chemotherapy (OR, 4.24; P = .002). Large RPLN showed higher discriminatory accuracy than high-risk Khorana score (AUROC, 0.71 v 0.67, respectively). Superior discriminatory accuracy of large RPLN over high-risk Khorana score was validated in the London cohort (AUROC, 0.61 v 0.57, respectively). CONCLUSION: Large RPLN is associated with VTE in patients with disseminated GCT and provides higher discriminatory accuracy than high-risk Khorana score. Results should be validated in larger, prospective studies. Prophylactic anticoagulation may be considered in high-risk patients.

Results of radiotherapy for primary subglottic squamous cell carcinoma.

PURPOSE: To retrospectively evaluate the outcome after radical radiotherapy (RT) and surgical salvage and assess the risk of late toxicity for patients with primary subglottic squamous cell carcinoma treated at our center. METHODS AND MATERIALS: Between 1971 and 1996, 43 patients with primary squamous cell carcinoma of the subglottis (35 men, 8 women) were treated with radical RT. All received megavoltage irradiation, most commonly to a dose of 50-52 Gy in 20 fractions during 4 weeks (39 patients). The median follow-up was 4.2 years. RESULTS: Local control was achieved with RT alone in 24 (56%) of the 43 patients: 7 of 11 with T1, 8 of 12 with T2, 4 of 8 with T3, and 5 of 12 with T4. The 5-year actuarial local relapse-free rate was 52%. Subsequent local control was achieved in 11 of the 13 patients with failed RT and attempted surgical salvage, for an ultimate local control rate of 81.4% (35 of 43). The 5-year overall and cause-specific actuarial survival rate was 50.3% and 66.9%, respectively. No patients developed Grade 3 or 4 late radiation morbidity. CONCLUSION: These data support the use of primary RT in the treatment of patients with primary squamous cell carcinoma of the subglottis as an appropriate treatment approach providing an option for laryngeal conservation.

Appropriate radiation volume for stage IIA/B testicular seminoma.

PURPOSE: Prophylactic left supraclavicular fossa irradiation has been suggested to reduce relapse rates in patients treated for Stage IIA/B testicular seminoma. To address this issue, we reviewed patterns of failure and treatment outcome in patients treated with radiation therapy at our institution. METHODS AND MATERIALS: Between 1981 and 1999, 79 men with Stage II seminoma (IIA, 49; IIB, 30) were treated with radiation therapy (RT) to the para-aortic and ipsilateral (+/- contralateral) pelvic lymph nodes (dose: 25-35 Gy). RESULTS: With a median follow-up of 8.5 years, the 5-year relapse-free rate was 91% (standard error: 3%), and 2 patients have died of seminoma, giving a 5-year cause-specific survival of 97%. A total of 7 patients have relapsed with 2 isolated to the left supraclavicular fossa. Five of 7 patients have been successfully salvaged. CONCLUSIONS: Prophylactic left supraclavicular fossa irradiation might have prevented relapse in 2 of 79 patients in Stage IIA/B seminoma. However, 97% of patients would have received unnecessary left neck RT, so we continue to recommend, as standard treatment, infradiaphragmatic RT only.

A comparison of published head and neck stage groupings in laryngeal cancer using data from two countries.

The combination of T, N, and M classifications into stage groupings is meant to facilitate a number of activities including: the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. We tested the UICC/AJCC fifth edition stage grouping and six other TNM-based groupings proposed for head and neck cancer for their ability to meet these expectations in laryngeal cancer using data from Ontario, Canada, and the area of Southern Norway surrounding Oslo. We defined four criteria to assess each grouping scheme: (1) the subgroups defined by T, N, and M comprising a given group within a grouping scheme have similar survival rates (hazard consistency); (2) the survival rates differ among the groups (hazard discrimination); (3) the prediction of cure is high (outcome prediction); and (4) the distribution of patients among the groups is balanced. We previously identified or derived a measure for each criterion, and the findings were summarized using a scoring system. The range of scores was from 0 (best) to 7 (worst). The data sets were population-based, with 861 cases from Ontario and 642 cases from Southern Norway. Clinical stage assignment was used and the outcome of interest was cause-specific survival. Summary scores across the seven schemes had similar ranges: 0.9 to 5.1 in Ontario and 1.8 to 5.7 in Southern Norway, but the ranking varied. Summing the scores across the two datasets, the TANIS-7 scheme (Head & Neck 1993;15:497-503) ranked first, and was ranked high in both datasets (first and second, respectively). The UICC/AJCC scheme ranked sixth out of seven schemes, and its ranking was fifth and seventh, respectively. UICC/AJCC stage groupings were defined without empirical investigation. When tested, this scheme did not perform best. Our results suggest that the usefulness of the TNM system could be enhanced by optimizing the design of stage groupings through empirical investigation.

Non-risk-adapted surveillance in clinical stage I nonseminomatous germ cell tumors: the Princess Margaret Hospital's experience.

BACKGROUND: Since 1981 Princess Margaret Hospital has used initial active surveillance (AS) with delayed treatment at relapse as the preferred management for all patients with clinical stage I nonseminomatous germ cell tumors (NSGCT). OBJECTIVE: Our aim was to report our overall AS experience and compare outcomes over different periods using this non-risk-adapted approach. DESIGN, SETTING, AND PARTICIPANTS: Three hundred and seventy-one patients with stage I NSGCT were managed by AS from 1981 to 2005. For analysis by time period, patients were divided into two cohorts by diagnosis date: initial cohort, 1981-1992 (n=157), and recent cohort, 1993-2005 (n=214). INTERVENTION: Patients were followed at regular intervals, and treatment was only given for relapse. MEASUREMENTS: Recurrence rates, time to relapse, risk factors for recurrence, disease-specific survival, and overall survival were determined. RESULTS AND LIMITATIONS: With a median follow-up of 6.3 yr, 104 patients (28%) relapsed: 53 of 157 (33.8%) in the initial group and 51 of 214 (23.8%) in the recent group. Median time to relapse was 7 mo. Lymphovascular invasion (p<0.0001) and pure embryonal carcinoma (p=0.02) were independent predictors of recurrence; 125 patients (33.7%) were designated as high risk based on the presence of one or both factors. In the initial cohort, 66 of 157 patients (42.0%) were high risk and 36 of 66 patients (54.5%) relapsed versus 17 of 91 low-risk patients (18.7%) (p<0.0001). In the recent cohort, 59 of 214 patients (27.6%) were high risk and 29 of 59 had a recurrence (49.2%) versus 22 of 155 low-risk patients (14.2%) (p<0.0001). Three patients (0.8%) died from testis cancer. The estimated 5-yr disease-specific survival was 99.3% in the initial group and 98.9% in the recent one. CONCLUSIONS: Non-risk-adapted surveillance is an effective, simple strategy for the management of all stage I NSGCT.

A cinematic magnetic resonance imaging study of milk of magnesia laxative and an antiflatulent diet to reduce intrafraction prostate motion.

PURPOSE: To determine the reduction of prostate motion during a typical radiotherapy (RT) fraction from a bowel regimen comprising an antiflatulent diet and daily milk of magnesia. METHODS AND MATERIALS: Forty-two patients with T1c-T2c prostate cancer voided the bladder and rectum before three cinematic magnetic resonance imaging scans obtained every 9 s for 9 min in a vacuum immobilization device. The MRIs were at baseline without bowel regimen (MRI-BL), before CT planning with bowel regimen (MRI-CT), and before a randomly assigned RT fraction (1-42) with bowel regimen (MRI-RT). A single observer tracked displacement of the posterior midpoint (PM) of the prostate. The primary endpoints were comparisons of the proportion of time that the PM was displaced >3 mm (PTPM3) from its initial position, and the secondary endpoints were comparisons of the reduction of initial rectal area, with and without the bowel regimen. RESULTS: The mean rectal area was: 13.5 cm(2) at MRI-BL, 12.7 cm(2) at MRI-CT, and 12.3 cm(2) at MRI-RT (MRI-BL vs. MRI-CT, p = 0.11; MRI-BL vs. MRI-CT, p = 0.07). Moving rectal gas alone (56%) and moving gas and stool (18%) caused 74% of intrafraction prostate motion. The PTPM3 was 11.3% at MRI-BL, 4.8% at MRI-CT, and 12.0% at MRI-RT (MRI-BL vs. MRI-CT, p = 0.12; MRI-BL vs. MRI-RT, p = 0.89). CONCLUSION: For subjects voiding their rectum before imaging, an antiflatulent diet and milk of magnesia laxative did not significantly reduce initial rectal area or intrafraction prostate motion.

No role for routine chest radiography in stage I seminoma surveillance.

BACKGROUND: After orchidectomy, the standard management options available for stage I seminoma are surveillance, adjuvant radiotherapy, or adjuvant chemotherapy. The optimal follow-up protocol for surveillance is yet to be determined but includes frequent chest radiography (CXR) and computed tomography (CT) scan of the abdomen and pelvis (CT-AP). OBJECTIVE: The purpose of this study was to identify the modality that first detected relapse and to assess the value of the CXR in this setting. DESIGN, SETTING, AND PARTICIPANTS: Five hundred twenty-seven patients with histologically confirmed stage I testicular seminoma were managed with surveillance at our institution between 1982 and 2005. Routine CXRs were performed with each CT-AP and were done every 4-6 mo for 7 yr and annually thereafter. The median follow-up was 72 mo (range: 1-193). MEASUREMENTS: Measurements included the 5-yr relapse rate, overall survival, and disease-free survival to determine the modality that first detected relapse disease. RESULTS AND LIMITATIONS: The 5-yr actuarial relapse rate for the 527 patients was 14%. The 5-yr disease-free survival and overall survival were 85.7% and 98.6%, respectively. Seventy-three patients (97.3%) had an abnormal CT-AP and a normal CXR at relapse. One patient (1.3%) had an abnormal CT-AP with pulmonary metastasis on CXR and CT chest scan, and one patient (1.3%) had a biopsy-proven inguinal node metastasis with a normal CXR. No patient had a normal CT-AP or physical examination with an abnormal CXR at relapse. This is a single-center retrospective study based on a relatively small number of relapses and may be subject to bias. Confirmation of these results from other studies would be useful for wider clinical applicability. CONCLUSIONS: All except one relapse were detected by CT-AP with no relapses detected on CXR alone; therefore, CXR may be omitted as routine imaging in surveillance protocols.

Image guided dose escalated prostate radiotherapy: still room to improve.

BACKGROUND: Prostate radiotherapy (RT) dose escalation has been reported to result in improved biochemical control at the cost of greater late toxicity. We report on the application of 79.8 Gy in 42 fractions of prostate image guided RT (IGRT). The primary objective was to assess 5-year biochemical control and potential prognostic factors by the Phoenix definition. Secondary endpoints included acute and late toxicity by the Radiotherapy Oncology Group (RTOG) scoring scales. METHODS: From October/2001 and June/2003, 259 men were treated with at least 2-years follow-up. 59 patients had low, 163 intermediate and 37 high risk disease. 43 had adjuvant hormonal therapy (HT), mostly for high- or multiple risk factor intermediate-risk disease (n = 25). They received either 3-dimensional conformal RT (3DCRT, n = 226) or intensity modulated RT (IMRT) including daily on-line IGRT with intraprostatic fiducial markers. RESULTS: Median follow-up was 67.8 months (range 24.4-84.7). There was no severe (grade 3-4) acute toxicity, and grade 2 acute gastrointestinal (GI) toxicity was unusual (10.1%). The 5-year incidence of grade 2-3 late GI and genitourinary (GU) toxicity was 13.7% and 12.1%, with corresponding grade 3 figures of 3.5% and 2.0% respectively. HT had an association with an increased risk of grade 2-3 late GI toxicity (11% v 21%, p = 0.018). Using the Phoenix definition for biochemical failure, the 5 year-bNED is 88.4%, 76.5% and 77.9% for low, intermediate and high risk patients respectively. On univariate analysis, T-category and Gleason grade correlated with Phoenix bNED (p = 0.006 and 0.039 respectively). Hormonal therapy was not a significant prognostic factor on uni- or multi-variate analysis. Men with positive prostate biopsies following RT had a lower chance of bNED at 5 years (34.4% v 64.3%; p = 0.147). CONCLUSION: IGRT to 79.8 Gy results in favourable rates of late toxicity compared with published non-IGRT treated cohorts. Future avenues of investigation for toxicity reduction include IMRT, margin reduction, and dose modulation targeted to sites of disease burden. Further work is required to maximize efficacy beyond that achieved through radiation dose escalation alone.

Prevention and management of osteoporosis in men receiving androgen deprivation therapy: a survey of urologists and radiation oncologists.

OBJECTIVES: To determine the current practice of clinicians in the diagnosis and management of osteoporosis among men taking androgen deprivation therapy (ADT), because ADT leads to decreased bone mineral density (BMD) and fractures. METHODS: We sent out a survey to Canadian urologists and radiation oncologists. The survey included questions about BMD testing, treatment practices, referral patterns, and risk of osteoporosis. RESULTS: The surveys were returned by 170 of 294 respondents (response rate 58%). Few respondents would obtain a baseline BMD in patients starting ADT. Forty percent would order a repeat BMD test after starting ADT if the baseline BMD were normal or unknown, but more than two thirds would if the baseline BMD showed osteoporosis. In men with a normal BMD starting ADT, respondents recommended weight-bearing exercises (58%), calcium (50%), vitamin D (47%), and bisphosphonate (6%) supplements. In men with osteoporosis at baseline, the use of nonprescription therapies increased slightly and bisphosphonate use increased to 44%. If osteoporosis were diagnosed, 11% would treat the patient themselves. The estimated risk of developing osteoporosis within 1 year of starting ADT with a normal baseline BMD ranged from 0% to 90% (median 20%). CONCLUSIONS: To our knowledge, this is the first survey of its kind. The key findings included that few physicians would order a baseline BMD test, would prescribe bisphosphonates for prevention but almost one half would consider bisphosphonates to treat established osteoporosis, and wide variations exist in the practice patterns and risk perception surrounding ADT-related osteoporosis. Evidence-based guidelines are needed to help physicians deal effectively with osteoporosis prevention and management among men taking ADT.