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BACKGROUND. The authors prospectively evaluated the late gastrointestinal (GI) and genitourinary (GU) toxicity and prostate‐specific antigen (PSA) control of magnetic resonance imaging (MRI)‐guided brachytherapy used as salvage for radiation therapy (RT) failure. METHODS. From October 2000 to October 2005, 25 men with a rising PSA level and biopsy‐proven, intraprostatic cancer at least 2 years after initial RT (external beam in 13 men and brachytherapy in 12 men) who had favorable clinical features (Gleason score ≤7, PSA < 10 ng/mL, negative pelvic and bone imaging studies), received MRI‐guided salvage brachytherapy to a minimum peripheral dose of 137 gray on a phase 1/2 protocol. Estimates of toxicity and cancer control were calculated using the Kaplan‐Meier method. RESULTS. The median follow‐up was 47 months. The 4‐year estimate of grade 3 or 4 GI or GU toxicity was 30%, and 13% of patients required a colostomy and/or urostomy to repair a fistula. An interval < 4.5 years between RT courses was associated with both outcomes with a hazard ratio of 12 (95% confidence interval [95% CI], 1.4–100; P = .02) for grade 3 or 4 toxicity and 25 (95% CI, 1.1–529; P = .04) for colostomy and/orurostomy. PSA control (nadir +2 definition) was 70% at 4 years. CONCLUSIONS. The current results indicated that MRI‐guided salvage brachytherapy in men who are selected based on presenting characteristics and postfailure PSA kinetics can achieve high PSA control rates, although complications requiring surgical intervention may occur in 10% to 15% of patients. Prospective randomized studies are needed to characterize the relative cancer control and toxicity after all forms of salvage local therapy. Cancer 2007. © 2007 American Cancer Society.

Patients with histologic grade 1 and grade 2 (except N3) are at low risk of DM. Patients with grade 2 and N3 or patients with grade 3 and N1 to N3 have a higher risk of distant metastases and should be considered for systemic treatment.

BACKGROUND This study was designed to estimate the rates of late genitourinary (GU) and rectal toxicity after magnetic resonance image (MRI)‐guided prostate brachytherapy exclusively or in conjunction with external beam radiation therapy (EBRT). METHODS Between November 1997 and April 2002, 201 patients with category T1C prostate carcinoma (according to the 2002 American Joint Committee on Cancer staging criteria), prostate specific antigen levels < 10 ng/mL, and biopsy Gleason score 3 + 4 disease were treated with MRI‐guided brachytherapy exclusively or in conjunction with EBRT. The MRI‐guided technique was designed to spare the urethra based on delivery of the prescription dose to the peripheral zone exclusively. The Kaplan–Meier method was used to estimate rates of freedom from late GU and rectal toxicity. Comparisons were made using a log‐rank test. RESULTS At a median follow‐up of 2.8 years (range, 0.5–5.0 years), the 4‐year estimates of rectal bleeding requiring coagulation for patients who underwent implantation therapy, compared with patients who received combined‐modality therapy, were 8% versus 30%, respectively (log‐rank P value = 0.0001). Although erectile dysfunction was common (range, 82–93%), with the use of sildenafil citrate (Viagra®), it was estimated that at least two‐thirds of patients had erectile function comparable to or superior to baseline function, independent of whether they received monotherapy or combined‐modality therapy (P = 0.46). The 4‐year estimate of freedom from radiation cystitis was 100% versus 95% (P = 0.01) for patients who received monotherapy and patients who received combined‐modality therapy, respectively. No urethral strictures were observed, and no patients underwent postimplantation transurethral resection of the prostate. CONCLUSIONS In the current study, rectal bleeding after MRI‐guided prostate brachymonotherapy was infrequent, and urethral and bladder toxicity is reported to be rare and may be attributed to the urethral‐sparing technique of the MRI‐guided approach. Cancer 2003;98:949–54. © 2003 American Cancer Society. DOI 10.1002/cncr.11595

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Purpose/Objective: Hypofractionated radiotherapy (HRT) regimens for prostate cancer are emerging, but tolerance doses for late adverse events are scarce. The purpose of this study is to define dose-volume predictors for late gastrointestinal and genitourinary (GI and GU) toxicities after HRT in the multi-center NRG/RTOG 0415 low-risk prostate cancer trial (N=521). Material/methods: Treatment in the studied HRT arm was delivered as 70Gy at 2.5Gy/fraction with 3D-CRT/IMRT (N=108/413). At a median follow-up of 5.9 years, the crude late ≥Grade 2 GI and GU toxicities were 19% and 29%, respectively. For modeling, the complete HRT cohort was randomly split into training and validation (70% and 30%; preserved toxicity rates). Within training, dose-response modeling was based on dose-volume cut-points (EQD2Gy; bladder/ rectum: α/β=6Gy/3Gy), age, acute ≥Grade 2 toxicity, and treatment technique using univariate and multivariate logistic regression on bootstrapping (UVA and MVA). Candidate predictors were determined at p≤0.05, and the selected MVA models were explored on validation where model generalizability was judged if the area under the receiver-operating curve in validation (AUC validation) was within AUC training ±SD with p≤0.05, and with an Hosmer-Lemeshow p-value (p HL)>0.05. Results: Three candidate predictors were suggested for late GI toxicity: the minimum dose to the hottest 5% rectal volume (D5%[Gy]), the absolute rectal volume <35Gy, and acute GI toxicity (AUC=0.59-0.63; p=0.02-0.04). The two generalizable MVA models, i.e.. D5%[Gy] with or without acute GI toxicity (AUC validation =0.64. 0.65; p=0.01, 0.03; p HL =0.45-0.56), suggest that reducing late GI toxicity from 20% to 10% would require reducing D5%[Gy] from ≤65Gy to ≤62Gy (logistic function argument: 17+(0.24D5%[Gy])). Acute GU toxicity showed only a trend to predict late GU toxicity (AUC training =0.57; p=0.07). Conclusion: Uate GI toxicity, following moderate HRT for low-risk prostate cancer, increases with higher doses to small rectal volumes. This work provides quantitative evidence that limiting small rectal dose 'hotspots' in clinical practice of such HRT regimens is likely to further reduce the associated rates of GI toxicity.

Purpose To investigate the dosimetric variability associated with interobserver organ-at-risk delineation differences on computed tomography in patients undergoing gynecologic interstitial brachytherapy. Methods and Materials The rectum, bladder and sigmoid of 14 patients treated with gynecologic interstitial brachytherapy were retrospectively contoured by 13 physicians. Geometric variability was calculated using κ statistics, conformity index (CIgen), and coefficient of variation (CV) of volumes contoured across physicians. Dosimetric variability of the single-fraction D0.1cc and D2cc was assessed through CV across physicians, and the standard deviation of the total EQD2 (equivalent dose in 2 Gy per fraction) brachytherapy dose (SDTOT) was calculated. Results The population mean ± 1 standard deviation of κ, CIgen and volume CV were, respectively: 0.77 ± 0.06, 0.70 ± 0.08 and 20% ± 6% for bladder; 0.74 ± 06, 0.67 ± 0.08 and 20% ± 5% for rectum, and 0.33 ± 0.20, 0.26 ± 0.17 and 82% ± 42% for sigmoid. Dosimetric variability was: for bladder, CV = 31% ± 19% (SDTOT = 72 ± 64 Gy) for D0.1cc and CV = 16% + 10% (SDTOT = 9 ± 6 Gy) for D2cc; for rectum, CV = 11% ± 5% (SDTOT = 16 ± 17 Gy) for D0.1cc and CV = 7% ± 2% (SDTOT = 4 ± 3 Gy) for D2cc; for sigmoid, CV = 39% ± 28% (SDTOT = 12 ± 18 Gy) for D0.1cc and CV = 34% ± 19% (SDTOT = 4 ± 4 Gy) for D2cc. Conclusions Delineation of bladder and rectum by 13 physicians demonstrated substantial geometric agreement and resulted in good dosimetric agreement for all dose-volume histogram parameters except bladder D0.1cc. Small delineation differences in high-dose regions by the posterior bladder wall may explain these results. The delineation of sigmoid showed fair geometric agreement. The higher dosimetric variability for sigmoid compared with rectum and bladder did not correlate with higher variability in the total brachytherapy dose but rather may be due to the sigmoid being positioned in low-dose regions in the cases analyzed in this study.

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