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Background: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined., Methods: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The primary objective was to assess whether the addition of ADT and docetaxel to ART resulted in a freedom from progression (FFP) rate ≥ 70% compared with an expected rate of 50%. Multivariate logistic and Cox regression analyses were used to model associations between factors and outcomes., Results: In total, 74 patients were enrolled. The median follow-up was 4.4 years. The pathologic tumor classification was pT2 in 4% of patients, pT3 in 95%, and pT4 in 1%. The Gleason score was 7 in 18% of patients and ≥8 in 82%. Post-RP PSA levels were ≤0.2 ng/mL in 53% of patients and >0.2 ng/mL in 47%. The 3-year FFP rate was 73% (95% confidence interval, 61%-83%), and the 3-year cumulative incidence of biochemical, distant, and local failure was 26%, 7%, and 0%, respectively. In multivariate models, postprostatectomy PSA nadir was associated with 3-year FFP, Gleason score, and PSA with biochemical failure. Grade 3 and 4 neutropenia was common; however, only 3 episodes of febrile neutropenia occurred. Late toxicities were not impacted by the addition of systemic therapy., Conclusions: Combined ADT, docetaxel, and ART for men with high-risk prostate cancer after prostatectomy exceeded the prespecified study endpoint of 70% 3-year FFP. Phase 3 trials assessing combined local and systemic therapies for these high-risk patients are warranted. Cancer 2017;123:2489-96. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Purpose: Prostate brachytherapy sometimes requires the volume receiving >150% of the prescribed dose (V150) to be >50% to obtain satisfactory coverage. There has been concern expressed that high V150 may be associated with higher rates of urinary retention and morbidity., Methods and Materials: We reviewed 207 consecutive cases of prostate brachytherapy treated with palladium 103 ((103)Pd; n = 140) or iodine 125 ((125)I; n = 67). Prescribed doses for (103)Pd monotherapy and boost were 124 and 90 Gy, respectively; for (125)I, the corresponding doses were 160 and 120 Gy. Patients were evaluated at baseline, 1 month, 3 months, and every 6 months thereafter., Results: Median follow-up at the time of analysis was 18 months. For (103)Pd, the mean intraoperative volume and V150 were 30.3 cm(3) and 72%, respectively; corresponding values for (125)I were 38.3 cm(3) and 59%, respectively. Two of the patients treated with iodine and 9 treated with palladium experienced acute urinary retention, which was not statistically significant (P = .48). The rectal V100 for (103)Pd was significantly less than that for (125)I (P < .001). The mean baseline, 1-month, and 12-month American Urologic Association (AUA) scores for (103)Pd were 8.5, 19.7, and 8.2, respectively; for (125)I, the values were 7.4, 17.1, and 13.4, respectively. At 12 months, the AUA scores returned to baseline in the (103)Pd-treated patients, whereas scores in (125)I-treated patients remained elevated (P = .005). High V150 did not appear to cause undue risk of urinary retention or morbidity based on logistic regression analysis of patients treated with monotherapy performed with either isotope., Conclusions: The risk of urinary retention was low, despite high V150 values for both isotopes. In patients treated with brachytherapy alone, no significant increase in urinary morbidity was seen in relation to V150. AUA scores returned to baseline in (103)Pd-treated patients at 1 year, whereas (125)I-treated patients demonstrated continued elevation., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

The structural maintenance of chromosome 1 (Smc1) protein is a member of the highly conserved cohesin complex and is involved in sister chromatid cohesion. In response to ionizing radiation, Smc1 is phosphorylated at two sites, Ser-957 and Ser-966, and these phosphorylation events are dependent on the ATM protein kinase. In this study, we describe the generation of two novel ELISAs for quantifying phospho-Smc1(Ser-957) and phospho-Smc1(Ser-966). Using these novel assays, we quantify the kinetic and biodosimetric responses of human cells of hematological origin, including immortalized cells, as well as both quiescent and cycling primary human PBMC. Additionally, we demonstrate a robust in vivo response for phospho-Smc1(Ser-957) and phospho-Smc1(Ser-966) in lymphocytes of human patients after therapeutic exposure to ionizing radiation, including total-body irradiation, partial-body irradiation, and internal exposure to (131)I. These assays are useful for quantifying the DNA damage response in experimental systems and potentially for the identification of individuals exposed to radiation after a radiological incident.

Purpose: A report of biochemical outcomes for patients treated with palladium-103 (Pd-103) brachytherapy over a fixed time interval., Methods and Materials: Two hundred thirty patients with clinical stage T1-T2 prostate cancer were treated with Pd-103 brachytherapy and followed with prostate-specific antigen (PSA) determinations. Kaplan-Meier estimates of biochemical failure on the basis of two consecutive elevations of PSA were utilized. Multivariate risk groups were constructed. Aggregate PSA response by time interval was assessed., Results: The overall biochemical control rate achieved at 9 years was 83.5%. Failures were local 3.0%; distant 6.1%; PSA progression only 4.3%. Significant risk factors contributing to failure were serum PSA greater than 10 ng/ml and Gleason sum of 7 or greater. Five-year biochemical control for those exhibiting neither risk factor was 94%; one risk factor, 82%; both risk factors, 65%. When all 1354 PSA determinations obtained for this cohort were considered, the patients with a proportion of PSAs < or = 0.5 ng/ml continued to increase until at least 48 months post-therapy. These data conformed to a median PSA half-life of 96.2 days., Conclusions: Prostate brachytherapy with Pd-103 achieves a high rate of biochemical and clinical control in patients with clinically organ-confined disease. PSA response following brachytherapy with low-dose-rate isotopes is protracted.

Purpose: To compare the prostate volumes defined by transrectal ultrasound (TRUS) versus computed tomographic (CT) scans used for brachytherapy planning., Methods and Materials: Ten unselected patients underwent evaluation for prostate brachytherapy with TRUS and CT imaging. Axial prostate contours were obtained at 5-mm intervals in both studies. The CT images were photographed, scanned into a commercial software program, and reprinted from a laser printer at 600 dots per inch to provide individual images that were interpreted independently by the three physician authors (BK, KW, and JB). An effort was made to exclude pelvic floor muscles from the defined prostate contour. Volumes were calculated in cubic centimeters. The prostate volume and maximum dimension in each plane were compared for each imaging modality., Results: The CT-based prostate volumes ranged from 31.1 cc to 48.1 cc. The TRUS-based volumes ranged from 26.6 cc to 46.4 cc. There was close agreement between imaging modalities (r = 0.9). The anterior-posterior, lateral, and craniocaudal prostatic dimensions were similar between modalities. To test for consistency between observers, the CT volumes were drawn independently by KB, KW, and JB. The prostatic measurements were consistent in all dimensions between observers., Conclusion: CT scan volumes and measurements correlate well with those obtained by TRUS, and are appropriate for pre- or postimplant dosimetry.

The purpose of the study was to determine which clinical parameters might predict individual prostate volume changes from prostate brachytherapy. Fifty consecutive, unselected patients treated at the University of Washington by I-125 or Pd-103 implantation for prostatic carcinoma in 1998 were analyzed. The prostate contours on preimplant transrectal ultrasound (TRUS) images were digitized and the prostate volumes calculated. Postimplant axial CT images of the prostate was obtained at 0.5 cm intervals with patients in the supine position the morning after the implant. The postimplant prostate volume increased by an average factor of 1.7 (+/-0.34) compared with the preimplant volume, the size increase being primarily in the anterior-posterior dimension. The absolute volume change was similar in patients with small vs. large preimplant prostate volume (r = -0.39), but the proportional change was less in patients with a larger prostate volume (r = -0.71). Because patients with a small preimplant prostate had proportionately greater volume increase, their postimplant target coverage was generally less. No single parameter, including preimplant prostate volume, preimplant hormonal deprivation, or supplemental external beam radiation therapy (EBRT) can accurately predict the degree of swelling. The precise significance of and practical solution to implant-related prostate volume changes remains to be determined.