High-dose-rate brachytherapy boost for prostate cancer: comparison of two different fractionation schemes.

PURPOSE: This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy × 3 fractions (patient group 1) and 950 cGy × 2 fractions (patient group 2). METHODS AND MATERIALS: A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy × 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy × 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score ≥7, and/or clinical stage T3 disease. RESULTS: Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. CONCLUSIONS: Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.

Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost.

PURPOSE: Permanent prostate implant brachytherapy (PPI), three-dimensional conformal radiotherapy (3D-CRT), and conformal proton beam radiotherapy (CPBRT) are used in the treatment of localized prostate cancer, although no head-to-head trials have compared these modalities. We studied the biochemical control (biochemical no evidence of disease [bNED]) and prostate-specific antigen (PSA) nadir achieved with contemporary PPI, and evaluated it against 3D-CRT and CPBRT. PATIENTS AND METHODS: A total of 249 patients were treated with PPI at the University of California, San Francisco, and the outcomes were compared with those from a 3D-CRT cohort and the published results of a high-dose CPBRT boost (CPBRTB) trial. For each comparison, subsets of the PPI cohort were selected with patient and disease criteria similar to those of the reference group. RESULTS: With a median follow-up of 5.3 years, the bNED rate at 5 and 7 years achieved with PPI was 92% and 86%, respectively, using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, and 93% using the PSA nadir plus 2 ng/mL definition. Using the ASTRO definition, a 5-year bNED rate of 78% was achieved for the 3D-CRT patients compared with 94% for a comparable PPI subset and 93% vs. 92%, respectively, using the PSA nadir plus 2 ng/mL definition. The median PSA nadir for patients treated with PPI and 3D-CRT was 0.10 and 0.40 ng/mL, respectively (p < .0001). For the CPBRT comparison, the 5-year bNED rate after a CPBRTB was 91% using the ASTRO definition vs. 93% for a similar group of PPI patients. A greater proportion of PPI patients achieved a lower PSA nadir compared with those achieved in the CPBRTB trial (PSA nadir < or =0.5 ng/mL, 91% vs. 59%, respectively). CONCLUSION: We have demonstrated excellent outcomes in low- to intermediate-risk patients treated with PPI, suggesting at least equivalent 5-year bNED rates and a greater proportion of men achieving lower PSA nadirs compared with 3D-CRT or CPBRTB.

High-dose-rate brachytherapy for localized prostate adenocarcinoma post abdominoperineal resection of the rectum and pelvic irradiation: Technique and experience.

PURPOSE: Treatment options are limited for patients with localized prostate cancer and a prior history of abdominoperineal resection (APR) and pelvic irradiation. We have previously reported on the successful utility of high-dose-rate (HDR) brachytherapy salvage for prostate cancer failing definitive external beam radiation therapy (EBRT). In this report, we describe our technique and early experience with definitive HDR brachytherapy in patients post APR and pelvic EBRT. PATIENTS AND METHODS: Six men with newly diagnosed localized prostate cancer had a prior history of APR and pelvic EBRT. Sixteen to 18 HDR catheters were placed transperineally under transperineal ultrasound-guidance. The critical first two catheters were placed freehand posterior to the inferior rami on both sides of the bulbar urethra under cystoscopic visualization. A template was used for subsequent catheter placement. Using CT-based planning, 5 men received 36Gy in six fractions as monotherapy. One patient initially treated with EBRT to 30Gy, received 24Gy in four fractions. RESULTS: Median age was 67.5 (56-74) years. At a median followup of 26 (14-60) months, all patients are alive and with no evidence of disease per the Phoenix definition of biochemical failure, with a median prostate-specific antigen nadir of 0.19ng/mL. Three men have reported grade 2 late genitourinary toxicity. There has been no report of grade 3-5 toxicity. CONCLUSION: Transperineal ultrasound-guided HDR brachytherapy using the above technique should be considered as definitive therapy for patients with localized prostate cancer and a prior history of APR and pelvic EBRT.

Inverse planning simulated annealing for magnetic resonance imaging-based intracavitary high-dose-rate brachytherapy for cervical cancer.

PURPOSE: To develop a technique using exclusively magnetic resonance imaging (MRI) to perform dwell position identification, targets and organs at risk delineation, and to apply inverse planning dose optimization to high-dose-rate brachytherapy for cervical cancer. METHODS AND MATERIALS: We included 15 consecutive women treated with high-dose-rate (HDR) brachytherapy for cervical cancer. All patients underwent MRI after placement of tandem and ring applicator containing a gadodiamide-filled dummy marker. This technique allowed direct visualization of the source pathway and precise definition of the intra-applicator source positions. For each patient, we delineated gross target volume (GTV), high-risk clinical target volume (HR-CTV), and organs at risk on MRI, according to the European Gynecological GEC-ESTRO Working Group definitions. We performed inverse planning simulated annealing (IPSA) and analyzed the dose-volume histograms with the following endpoints: D(90), D(100), and V(100) for GTV and HR-CTV; D0.1 cc, D1 cc, D2 cc for bladder, rectum, and bowel; and dose at Point A. RESULTS: The intra-applicator source pathway was easily visualized on MRI using the gadodiamide-filled marker. IPSA provided excellent target coverage. The mean D(90) and V(100) for HR-CTV were 103+/-5% and 92+/-3%, respectively. IPSA provided excellent bladder sparing. D1 cc and D2 cc of bladder were 73+/-10% and 67+/-10%, respectively. CONCLUSIONS: We developed a novel technique that allows direct visualization of the intra-applicator source pathway on MRI. Using this technique, we successfully performed inverse planning directly from MRI.

Advances in the treatment of localized prostate cancer: the role of anatomic and functional imaging in men managed with radiotherapy.

Radiation therapy is an active modality in the management of local and regional prostate cancer, but can be curative only if all existing disease is encompassed within the treatment portal. In addition to the ability to deliver sufficient radiation dose, accurate targeting is critical to achieve better treatment outcomes. Failure to accommodate daily variations in setup and organ motion potentially limits the efficacy of sophisticated conformal techniques (three-dimensional conformal radiotherapy and intensity-modulated radiotherapy). Increased use of various online and real-time imaging techniques is an important step toward enhancing treatment accuracy. The incorporation of functional imaging techniques into treatment planning is another important step. The addition of biologic and metabolic information regarding the location and extent of disease combined with real-time online imaging will allow us to better determine where, how, and with what to treat appropriate targets and improve cure rates.

New techniques and management options for localized prostate cancer.

Prostate cancer is diagnosed in younger men who want treatment that does not compromise their quality of life, take time away from work, or cause worrisome side effects. Laparoscopic radical prostatectomy, robot-assisted laparoscopic radical prostatectomy, and third-generation cryotherapy are modifications of previously used techniques in the treatment of prostate cancer and are presented in this article. Although some or all of the outcomes might be expected to change in the future, the urologic surgeon is left to select an approach, presumably on the basis of the experience, level of training, and care pathways at his or her institution.

Radiotherapy in the management of common genitourinary malignancies.

A continued role for radiation therapy in the multidisciplinary management of genitourinary malignancies seems certain. Treatment outcomes continue to improve, accompanied by diminishing rates of toxicity. With continued technologic advances in the delivery of radiation, including the use of adaptive radiotherapy, the discovery and application of novel treatment agents, and the combined efforts of urologists, medical oncologists, and radiation oncologists, patients who have genitourinary malignancies have an excellent chance of cure.

Radiotherapy in the management of clinically localized prostate cancer: evolving standards, consensus, controversies and new directions.

Major advances have been made in the definitive use of various forms of radiotherapy (RT) in the management of clinically localized prostate cancer (PCa). Despite tremendous gains, the radiation oncology community continues to struggle with several key questions. In general, the areas of controversy pertain to how to improve the therapeutic ratio of RT. Specifically, key issues include dose escalation; the relative benefit of alternative forms of RT (ie, brachytherapy and protons); target localization; the use, timing, and duration of androgen deprivation; and the need for pelvic nodal irradiation. Multiple efforts have been made to address each of these issues; however, there is no consensus on how to resolve them. This review is an evidence-based critique of the available treatment approaches considered for the optimal use of radiotherapy as definitive management of clinically localized PCa.

Androgen deprivation use with external beam radiation for prostate cancer: results from CaPSURE.

PURPOSE: Recent data support the role of androgen deprivation in men undergoing external beam radiotherapy for prostate cancer. The benefits of neoadjuvant, concurrent or adjuvant treatment have been limited to men at intermediate and high risk. We examined the patterns and predictors of androgen deprivation in men undergoing external beam radiation therapy in CaPSURE. MATERIALS AND METHODS: CaPSURE is an observational, longitudinal disease registry, from which 932 men met study inclusion criteria. Androgen deprivation was classified as neoadjuvant-within 9 months of radiation or adjuvant-from the start of radiation to 6 months after completion. Time trends in androgen deprivation as well factors associated with combined therapy were elucidated using multivariate analyses. RESULTS: In this study 40%, 39% and 21% of men could be categorized into high, intermediate and low risk groups, respectively. Overall 42% and 33% of patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. Between 1997 and 2002 neoadjuvant hormone use increased significantly in all risk groups, including patients at low risk. On multivariate analyses only the year of diagnosis and clinical risk group were associated with receiving androgen deprivation with radiation. CONCLUSIONS: A significant increase in combined androgen deprivation and external radiation was observed in the last decade in men with intermediate and high risk disease. Nevertheless, more widespread acceptance is necessary since a substantial minority continue to receive radiation alone. Many patients with low risk disease that is amenable to radiation monotherapy also receive androgen deprivation. No clinical or sociodemographic features predicted the use of androgen deprivation with external radiation.

Longitudinal assessment of changes in sexual function and bother in patients treated with external beam radiotherapy or brachytherapy, with and without neoadjuvant androgen ablation: data from CaPSURE.

PURPOSE: To evaluate the effects of external beam radiotherapy (EBRT), with or without brachytherapy (BT) boost or brachytherapy monotherapy with and without short-term androgen ablation (<==6 months; STAD) on sexual function (SF) and sexual bother (SB) in men treated for localized prostate cancer. METHODS AND MATERIALS: A total of 992 men with newly diagnosed prostate cancer enrolled in the Cancer of the Prostate Strategic Urological Research Endeavor database were studied to assess treatment-related changes in SF and SB. Six treatment subgroups (EBRT - STAD, EBRT + STAD, BT - STAD, BT + STAD, EBRT + BT - STAD, EBRT + BT + STAD) were compared. RESULTS: The greatest reported changes in SF occurred during the first 2 posttreatment years. Patients receiving BT reported greater SF and the least change in SF overall; those receiving EBRT + BT reported the greatest decline in SF. SF scores associated with STAD were initially lower than in patients without STAD; however by 1 year no statistically significant difference in SF or SB was noted. CONCLUSION: Each treatment for prostate cancer can negatively affect SF and SB. Initial differences among treatment subgroups exist, but diminish with time. SF changes associated with EBRT +/- BT were statistically significant and those for BT were not. STAD appeared to confer only temporary and recoverable impairment of erectile function.

Radical pleurectomy/decortication and intraoperative radiotherapy followed by conformal radiation with or without chemotherapy for malignant pleural mesothelioma.

OBJECTIVES: We performed a retrospective review of the efficacy and morbidity of radical pleurectomy/decortication and intraoperative radiotherapy followed by external beam radiation therapy with or without chemotherapy for diffuse malignant pleural mesothelioma. METHODS: A total of 32 patients with diffuse malignant pleural mesothelioma were initially evaluated between January 1995 and September 2000. Three patients were excluded from analysis because of unresectable disease. Two patients died postoperatively, and one patient had recurrent disease previously treated at an outside institution. Of the remaining 26 patients included in the analysis, 24 received intraoperative radiotherapy. External beam radiation therapy was generally started 1 to 2 months after resection and delivered by means of 3-dimensional conformal radiation therapy or with inverse treatment planning intensity-modulated radiation therapy. When given, chemotherapy consisted of 2 to 3 cycles of cyclophosphamide, doxorubicin (Adriamycin), and cisplatin initiated 1 to 2 months after completion of radiation. RESULTS: At the time of data analysis, 5 of 26 patients were alive. The median follow-up was 9.7 months (range, 2-67.6 months). The median overall survival and progression-free interval from the time of the operation were 18.1 and 12.2 months, respectively. The Kaplan-Meier estimates of overall survival and freedom from progression at 1 year were 64% and 50%, respectively. The site of failure was mostly locoregional. However, there were 4 abdominal failures and 1 contralateral lung failure. CONCLUSIONS: Radical pleurectomy/decortication with aggressive radiotherapy with or without chemotherapy might offer an alternative treatment option to those who cannot tolerate extrapleural pneumonectomy.