First Report of NRG Oncology/Radiation Therapy Oncology Group 0622: A Phase 2 Trial of Samarium-153 Followed by Salvage Prostatic Fossa Irradiation in High-Risk Clinically Nonmetastatic Prostate Cancer After Radical Prostatectomy.

PURPOSE: To investigate the utility of 153Sm lexidronam (Quadramet) in the setting of men with prostate cancer status post radical prostatectomy who develop biochemical failure with no clinical evidence of osseous metastases. PATIENTS AND METHODS: Trial NRG Oncology RTOG 0622 is a single-arm phase 2 trial that enrolled men with pT2-T4, N0-1, M0 prostate cancer status post radical prostatectomy, who meet at least 1 of these biochemical failure criteria: (1) prostate-specific antigen (PSA) > 1.0 ng/mL; (2) PSA > 0.2 ng/mL if Gleason score 9 to 10; or (3) PSA > 0.2 ng/mL if N1. Patients received 153Sm (2.0 mCi/kg intravenously × 1) followed by salvage external beam radiation therapy (EBRT) to the prostatic fossa (64.8-70.2 Gy in 1.8-Gy daily fractions). No androgen deprivation therapy was allowed. The primary objective was PSA response within 12 weeks of receiving 153Sm. The secondary objectives were to: (1) assess the completion rate for the regimen of 153Sm and EBRT; (2) evaluate the hematologic toxicity and other adverse events (AEs) at 12 and 24 weeks; and (3) determine the freedom from progression rate at 2 years. RESULTS: A total of 60 enrolled eligible patients were included in this analysis. Median follow-up was 3.97 years. A PSA response was achieved in 7 of 52 evaluable patients (13.5%), compared with the 25% hypothesized. The 2-year freedom from progression rate was 25.5% (95% confidence interval 14.4%-36.7%), and the biochemical failure rate was 64.4% (95% CI 50.5%-75.2%). Samarium-153 was well tolerated, with 16 (of 60) grade 3 to 4 hematologic AEs and no grade 5 hematologic AEs. Radiation therapy was also well tolerated, with no grade 3 to 5 acute radiation therapy-related AEs and 1 grade 3 to 4 and no grade 5 late radiation therapy-related AEs. CONCLUSIONS: Trial NRG Oncology RTOG 0622 did not meet its primary endpoint of PSA response, although the regimen of 153Sm and salvage EBRT was well tolerated. Although the toxicity profile supports study of 153Sm in high-risk disease, it may not be beneficial in men receiving EBRT.

Successful management of female urethral carcinoma with radiation therapy and concurrent chemotherapy.

► Successful treatment of locally advanced urethral carcinoma with chemoradiation as evidenced by patients alive NED at 90 and 47 months. ► 45 Gy of external beam RT followed by 15-25 Gy of interstitial brachytherapy. ► Concurrent chemotherapy with 5-fluorouracil and cisplatin.

Quality of life after open or robotic prostatectomy, cryoablation or brachytherapy for localized prostate cancer.

PURPOSE: Health related quality of life concerns factor prominently in prostate cancer management. We describe health related quality of life impact and recovery profiles of 4 commonly used operative treatments for localized prostate cancer. MATERIALS AND METHODS: Beginning in February 2000 all patients treated with open radical prostatectomy, robot assisted laparoscopic prostatectomy, brachytherapy or cryotherapy were asked to complete the UCLA-PCI questionnaire before treatment, and at 3, 6, 12, 18, 24, 30 and 36 months after treatment. Outcomes were compared across treatment types with statistical analysis using univariate and multivariate models. RESULTS: A total of 785 patients treated between February 2000 and December 2008 were included in the analysis with a mean followup of 24 months. All health related quality of life domains were adversely affected by all treatments and recovery profiles varied significantly by treatment type. Overall urinary function and bother outcomes scored significantly higher after brachytherapy and cryotherapy compared to open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. Brachytherapy and cryotherapy had a 3-fold higher rate of return to baseline urinary function compared to open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. Sexual function and bother scores were highest after brachytherapy, with a 5-fold higher rate of return to baseline function compared to cryotherapy, open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. All 4 treatments were associated with relatively transient and less pronounced impact on bowel function and bother. CONCLUSIONS: In a study of sequential health related quality of life assessments brachytherapy and cryotherapy were associated with higher urinary function and bother scores compared to open radical prostatectomy and da Vinci prostatectomy. Brachytherapy was associated with higher sexual function and bother scores compared to open radical prostatectomy, robotic assisted laparoscopic radical prostatectomy and cryotherapy.

Prospective longitudinal comparative study of early health-related quality-of-life outcomes in patients undergoing surgical treatment for localized prostate cancer: a short-term evaluation of five approaches from a single institution.

BACKGROUND AND PURPOSE: Quality of life (QoL) issues are a vital concern for the majority of patients seeking therapeutic intervention once they are found to have prostate cancer. A prospective longitudinal comparison using validated QoL instruments is a valuable technique to evaluate outcome differences. We evaluated the short-term QoL changes from baseline of five surgical approaches for localized prostate carcinoma delivered at a single institution. PATIENTS AND METHODS: A prospective longitudinal survey of 719 patients with newly diagnosed prostate cancer was initiated in 2001. The surgical procedures performed during this time period were open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP), da Vinci robotic prostatectomy (dVP), (103)Pd brachytherapy ((103)Pd), and prostate cryoablation (PCryo). An Institutional Review Board-approved questionnaire comprised of validated QoL instruments (UCLA Prostate Cancer Index and American Urological Association Symptom Index [SI]) was mailed to enrolled patients prior to their selected surgery and again at 1, 3, 6, 9, 12, 18, 24, and 36 months after therapy. A percent of baseline score calculation including data from all five treatment cohorts for follow-up months 1, 3, and 6 was compared within groups. Group I consisted of patients undergoing ORP, LRP, or dVP. Group II consisted of patients undergoing (103)Pd or PCryo. RESULTS: Between January 2000 and April 2005, 498 patients (69%) were enrolled who completed the baseline questionnaire and at least one follow-up survey at 1, 3, or 6 months. The mean patient age at ORP, LRP, dVP, (103)Pd, and PCryo was 59, 61, 60, 67, and 72 years, respectively. Within Group I, early recovery of sexual function (at 3 months) appeared to occur sooner after dVP (35% return to baseline [RTB]) than ORP (24% RTB) and LRP (21% RTB) (P = 0.03). No other significant differences were noted, and trends toward improvement were seen in all groups. Within Group II, PCryo (18% RTB) had a more negative impact on sexual function at 3 months than did 103Pd (63% RTB) (P = 0.007), although a significant difference in baseline sexual function was also noted (P = 0.001). Early urinary function (at 1 month) was better after (103)Pd (82% RTB) than PCryo (72%) (P = 0.05), but this difference was lost at 6 months. In addition, the irritative and obstructive symptoms evaluated by the AUA SI were significantly worse (P = 0.003) at 3 months after (103)Pd than after PCryo. CONCLUSIONS: Different surgical approaches for the treatment of localized prostate cancer affect the shortterm QoL results in different ways. Urinary, sexual, and bowel function and bother are affected to a similar degree by ORP, LRP, and dVP. In an older population, the tissue destruction resulting from PCryo appears to relieve obstructive and irritative urinary symptoms but at the sacrifice of sexual function compared with (103)Pd.

Prospective longitudinal comparative study of health-related quality of life in patients undergoing invasive treatments for localized prostate cancer.

BACKGROUND AND PURPOSE: Health-related quality of life (QoL) concerns are important for patients selecting treatment options for clinically localized prostate cancer and are critical in evaluating outcomes. We report pretreatment and post-treatment general and disease-specific QoL for the following invasive interventions: open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP), and palladium-103 ((103)Pd) brachytherapy. PATIENTS AND METHODS: We performed a prospective longitudinal survey of 452 patients with newly diagnosed prostate cancer treated at a single medical center between 2001 and 2003. An Institutional Review Board-approved questionnaire comprised of validated QoL instruments was sent to patients scheduled to undergo ORP (N = 186), LRP (N = 116), or brachytherapy (N = 150). The same questionnaire was sent out 1, 3, 6, 9, and 12 months after therapy. Comparisons were made between the groups to determine if the choice of therapy resulted in differences in QoL. RESULTS: General QoL scores were minimally affected by the choices; however, the disease-specific domains of bowel, urinary, and sexual function were adversely affected by all modalities. The ORP and LRP groups were similar among disease-specific domains and received lower post-treatment urinary and sexual scores than the (103)Pd patients. At 12 months, 38% of ORP and 46% of LRP patients had returned to baseline urinary function compared with 75% of (103)Pd patients. At 12 months, 63% of (103)Pd patients had returned to baseline sexual function compared with 19% of both the LRP and ORP patients. CONCLUSIONS: Invasive treatments for localized prostate cancer have little impact on general QoL but significantly affect disease-specific domains. Both ORP and LRP have a greater initial negative impact on urinary and sexual function than (103)Pd. The differences among the treatments with regard to QoL provide information to patients faced with choosing a treatment.

Contemporary management of prostate cancer with lethal potential.

Screening for prostate cancer by determining serum prostate-specific antigen (PSA) levels has resulted in a stage migration such that patients with high-risk disease are more likely to be candidates for curative local therapy. By combining serum PSA, clinical stage, and biopsy information--both Gleason score and volume of tumor in the biopsy cores--specimen pathologic stage and patient biochemical disease-free survival can be estimated. This information can help patients and clinicians understand the severity of disease and the need for multimodal therapy, often in the context of a clinical trial. While the mainstays of treatment for local disease control are radical prostatectomy and radiation therapy, systemic therapy must be considered as well. A randomized trial has shown a survival benefit for radical prostatectomy in patients with positive lymph nodes who undergo immediate adjuvant androgen deprivation. Clinical trials are needed to clarify whether adjuvant radiation therapy after surgery confers a survival benefit. PSA is a sensitive marker for follow-up after local treatment and has proven that conventional external-beam irradiation alone is inadequate treatment for high-risk disease. Fortunately, the technology of radiation delivery has been dramatically improved with tools such as three-dimensional conformal radiation, intensity-modulated radiation therapy, and high-dose-rate brachytherapy. The further contributions of pelvic irradiation and neoadjuvant, concurrent, and adjuvant androgen deprivation therapy have been defined in clinical trials. Future management of high-risk prostate cancer may be expanded by clinical trials evaluating neoadjuvant and/or adjuvant chemotherapy in combination with androgen deprivation.

High-dose-rate brachytherapy of recurrent rectal adenocarcinoma presenting as a solitary intravascular metastasis of the iliac vein: a case report.

PURPOSE: To describe a novel use of high-dose-rate intravascular brachytherapy in the first reported case of macroscopic metastatic rectal adenocarcinoma within a peripheral vein. METHODS AND MATERIALS: Following thrombolytic therapy to ablate an overlying venous thrombosis, a vascular stent was deployed across the entire length of the tumor. Using the stent as a target, 4300 cGy was delivered to the tumor via megavoltage external beam radiation. This was followed by two weekly intravascular high-dose-rate 192Ir brachytherapy applications of 400 cGy each. RESULTS: There is no evidence of recurrence in the treated vein at 43 months of follow-up. CONCLUSIONS: In this unique case, a combination of external beam radiation therapy and intravascular brachytherapy provided effective control of a solitary intravascular metastasis from rectal carcinoma.