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Purpose: To quantify the dosimetric deviations that would arise from delivering subsequent prostate high-dose-rate fractions with only needle readjustment and no replanning after the first fraction., Methods and Materials: Patients were treated with either two implant sessions (two 9.5-Gy fractions per session) separated by 2-4 weeks or with one implant session and external beam radiotherapy. After needle placement, needle positions were adjusted under CT guidance, after which dosimetric planning was performed before each fraction. To evaluate the consequence of not replanning before the second fraction, we analyzed the dosimetric parameters of 45 consecutive implants (26 patients). Needles with optimized dwell positions from the first fraction were transferred to the needle positions in the second fraction. Needle displacement between fractions was assessed as well as changes in plan metrics., Results: After adjustment, the mean interfractional needle displacement was 3.5 mm. If replanned, the probability of planning target volume D90% ≥ 95% is 100%, prostate V100% ≥ 95% is 87%, and urethra V115% ≤10% is 78%. If treated without replanning, the probability of planning target volume D90% ≥ 95% is 82%, prostate V100% ≥ 95% is 53%, and urethra V115% ≤ 10% is 69%. Even for implants with minimal needle displacement (<3 mm) and minimal prostate volume change (<3 cc), the dosimetric consequence of not replanning the second fraction would result in 46% of cases with a prostate V100% < 95%., Conclusion: The dosimetric consequences of not replanning the second fraction for prostate high-dose-rate implants results in significantly inferior plan metrics., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

High-dose-rate brachytherapy is a relatively new radiotherapeutic intervention that is used as a curative treatment for patients with many types of cancer. Advances in mechanical systems and computer applications result in a sophisticated treatment technique that reliably delivers a high-quality radiation dose distribution to the intended target. Patients with localized prostate cancer may benefit from high-dose-rate brachytherapy, which may be used alone in certain circumstances or in combination with external-beam radiotherapy in other settings. The authors comprehensively searched the MEDLINE database for clinical studies published from January 1, 2002, through December 31, 2007, using the key terms brachytherapy, high-dose-rate, and prostatic neoplasms. Criteria for study review were study design, English language, relevance to clinicians, and validity based on design and appropriateness of conclusions. The abstract proceedings of meetings sponsored by the American Brachytherapy Society and the American Society for Therapeutic Radiology and Oncology were reviewed to identify additional relevant material. These sources provided the basis for a concise review of the rationale and advantages of high-dose-rate brachytherapy in the management of localized prostate cancer, as well as the details of the clinical use and therapeutic outcomes of this treatment as observed in a contemporaneous time frame.

Background: The role of radiotherapy (RT) for rising PSA after radical prostatectomy (RP) is debatable. We analyzed a large database of men to evaluate for predictors of prostate-specific antigen (PSA) failure after salvage RT., Methods: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor database (CaPSURE) identified 4,563 men with RP between 1989 and 2004; 194 underwent salvage RT > or = 6 months after RP. PSA failure following RT was defined as a PSA >0.2 ng/ml. The association between clinical and pathologic characteristics and PSA failure was examined using a chi-square metric. A multivariable analysis of predictors for time to PSA failure was performed using a Cox proportional hazard regression model., Results: After a median follow-up of 66 months, 121 (62%) men experienced PSA failure at a median 20 months. Significant associations for PSA failure were found for the clinical T category (P < .01), race/ethnicity (P = 0.04), pT3 disease (P < 0.01), seminal vesicle invasion (P < 0.01), and pre-RT PSA level (P < 0.01). The pre-RT PSA level (P = 0.07) was the only factor to approach significance as an independent predictor of PSA failure on multivariable analysis. Pre-RT PSA doubling time was calculated for 131 men but did not predict for PSA failure on univariate (P = 0.38) or multivariate analyses (P = 0.13) for < or = 12 vs. >12 months., Conclusions: Salvage RT provided the greatest benefit in PSA control in men with the lowest pre-RT PSA levels. Post-RP PSA doubling time >12 months trended toward predicting for PSA failure but was not significant likely owing to limited sample size. Together, these findings would suggest that salvage RT is optimal at low pre-RT PSA and long doubling times with favorable pathologic features.

Objectives: To analyze an observational database of prostate cancer, assessing for patterns of use and predictors of prostate-specific antigen (PSA) recurrence after adjuvant radiotherapy (RT)., Methods: From the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), 5336 men underwent prostatectomy from 1989 to 2004. Of these 5336 men, 96 men (1.8%) underwent adjuvant RT. These 96 men were classified as having low (Stage T1c-T2a and PSA level of 10 ng/mL or less and Gleason score of 6 or less), intermediate (Stage T2b or PSA level greater than 10 ng/mL and 20 ng/mL or less or Gleason score 7), or high (Stage T2c or higher or PSA level greater 20 ng/mL or Gleason score of 8 or greater) risk of PSA recurrence. PSA recurrence was defined as two consecutive PSA levels greater than 0.2 ng/mL. Differences between patients who experienced failure were assessed by chi-square tests or analysis of variance. Univariate and multivariate analyses were performed using a Cox proportional hazard regression model., Results: Of the 96 men, 27 (28%) experienced PSA failure and 20 (21%) received additional treatment, with a median of 60 months of follow-up. The clinical risk group (P <0.01), PSA level at diagnosis (P <0.01), Gleason score (P <0.01), and seminal vesicle invasion (P <0.01) all significantly associated with PSA recurrence. The clinical risk group was the sole predictor of PSA recurrence-free survival on multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.7 to 8.3, P = 0.007)., Conclusions: Adjuvant RT was not frequently used in men enrolled in CaPSURE. PSA recurrence was observed more frequently in men with high-risk disease, suggesting that adjuvant RT is not adequate therapy and that these men might benefit from the combined use of hormonal therapy and RT.

Objectives: To analyze the prostate-specific antigen (PSA) outcome after low-dose adjuvant RT at a single institution, because the role and optimal dose of external beam radiotherapy (RT) after radical prostatectomy for prostate cancer remain controversial., Methods: We retrospectively identified 65 men who had received low-dose adjuvant RT (median 50 Gy) for microscopically positive margins with an undetectable postoperative PSA from 1990 to 2004. Biochemical failure-free survival was the primary endpoint. Biochemical failure was defined as two consecutive PSA increases to greater than 0.2 ng/mL., Results: At a median follow-up of 5 years, 2 men had developed distant metastasis, 2 had local recurrence, and 2 had died (neither attributable to prostate cancer). Biochemical failure had occurred in 7 men (11%). The 5 and 8-year rate of biochemical failure-free survival was 87%. A greater Gleason score (P = 0.04) and seminal vesicle invasion (P = 0.04) predicted significantly for increased biochemical failure on univariate analysis. No single factor was significant on multivariate analysis. Men with a Gleason score of 7 or less had a 5-year biochemical failure-free survival rate of more than 90%. In contrast, those with a Gleason score of 8 or more had a 50% risk of biochemical failure at 5 years. Acute bowel or bladder toxicity (all grade 2 or less) developed in 25%. Two men developed chronic urethral stricture requiring dilation, and 34 (51%) developed surgery-related toxicity that persisted throughout and after RT., Conclusions: Low-dose RT is well tolerated and can potentially provide PSA control in men with Gleason score 7 or less disease with positive surgical margins after radical prostatectomy.

Purpose: This study was performed to evaluate the results and prognostic factors associated with radiotherapy for a detectable serum prostate specific antigen level after radical prostatectomy., Materials and Methods: From July 1987 through July 2003, 368 patients received radiotherapy for a detectable prostate specific antigen level (biochemical relapse) as the sole evidence of recurrence after radical prostatectomy for node negative prostate cancer. Estimated survival and relapse-free probabilities were obtained via Kaplan-Meier estimation. Associations of patient factors with survival and biochemical relapse were investigated using Cox proportional hazards models., Results: With a median followup of 5 years the 5 and 8-year freedom from biochemical relapse were an estimated 46% (95% CI 41%-53%) and 35% (95% CI 29%-43%) while survival was 92% (95% CI 89%-95%) and 80% (95% CI 74%-87%), respectively. Patient and treatment variables showing evidence of association with biochemical relapse on multivariate analysis included pathological stage T3a or less vs T3b (seminal vesicle involvement, p = 0.029), pathological Gleason score 7 or less vs 8 or greater (p <0.001) and pre-radiotherapy prostate specific antigen (p <0.001). Four biochemical failure risk groups were created by assigning seminal vesicle involvement, Gleason score and pre-radiotherapy prostate specific antigen each a score of 0 to 2. These individual scores were summed. The freedom from biochemical failure at 5 years for each risk group was 0 to 1-69%, 2-53%, 3-26% and 4 to 5-6%., Conclusions: The presence of seminal vesicle involvement and high Gleason score in the radical prostatectomy specimen are inherent predictors of adverse outcome. Early referral for salvage radiotherapy can decrease subsequent biochemical relapse.

Objectives: To compare, in a retrospective analysis, the outcome of salvage external beam radiotherapy (EBRT) for isolated prostate-specific antigen (PSA) elevation or palpable local recurrence after radical prostatectomy (RP)., Methods: We evaluated 102 men who underwent EBRT from 1993 to 1999, 60 for a rising PSA level alone and 42 for palpable local disease after RP. Biochemical disease-free survival and overall survival were calculated. Prognostic factors were evaluated to determine associations with biochemical disease-free survival., Results: The 5-year rate of biochemical disease-free survival, local control, freedom from distant metastasis, and overall survival for all 102 patients was 38%, 94%, 87%, and 88%, respectively. All palpable disease resolved completely after salvage EBRT. The greatest 5-year rate of biochemical control (69%) was obtained in patients with a pre-EBRT PSA level of 0.5 ng/mL or less. The 5-year overall survival rate was significantly better for those who underwent salvage EBRT for a rising PSA level than for those with palpable recurrence (96% versus 78%, P = 0.02). A low pre-EBRT PSA level and a less than 2-year interval from RP to EBRT were independent predictors of biochemical failure. Five patients (5%) experienced chronic grade 3 or 4 RT-related toxicity., Conclusions: Salvage EBRT provides excellent local control of recurrent disease after RP. Salvage EBRT before the development of palpable local disease may confer a survival benefit and decrease the risk of metastasis, and durable biochemical control was achieved best in those whose pre-EBRT PSA level was 0.5 ng/mL or less. Early referral and careful patient selection is vital for salvage EBRT to be of optimal benefit.

Purpose: A retrospective study to evaluate the outcome of salvage radiotherapy (RT) for clinically apparent, palpable prostate cancer recurrence after radical prostatectomy (RP)., Methods and Materials: Forty-two patients underwent RT for clinically apparent recurrent prostate cancer after RP between 1993 and 1999. The end points and treatment variables of biochemical disease-free survival were evaluated statistically., Results: The median follow-up was 4.3 years. All 42 patients experienced resolution of clinically detectable recurrence within 1 year after RT. The 5-year biochemical disease-free survival, local control, freedom from distant metastases, and overall survival rate was 27%, 94%, 82%, and 78%, respectively. The initial pathologic stage (T3 or T4; p = 0.04) and interval (<2 years from RP to RT; p = 0.01) were independent predictors of biochemical failure, and RT simulation without contrast (p = 0.05) was nearly significant on multivariate analysis. Three patients (7%) experienced chronic Grade 3 or 4 RT-related toxicity., Conclusion: Salvage prostate bed RT for clinically apparent locally recurrent prostate cancer after RP provides effective local tumor control with modest durable biochemical control. Patients irradiated with a better simulation technique were found to have a more favorable outcome. A consensus on a definition of biochemical disease-free survival after salvage RT is critical for meaningful comparison of the available data and to future progress in treating this disease process.

Controversy exists regarding the management of recurrent disease, heralded by a rising prostate specific antigen (PSA), in men who have undergone primary treatment of prostate cancer by radical prostatectomy. Although retrospective in nature, the use of salvage radiation therapy (RT) after prostatectomy has been extensively investigated and reported. Salvage RT alone is likely not optimal for every man presenting with recurrent disease after RP. Those with palpable recurrent disease or unfavorable disease characteristics are less likely to benefit from salvage RT alone and may respond better to a combined modality approach. However, early referral and proper patient selection maximizes the potential for durable biochemical control after salvage RT in men with rising PSA alone.

Purpose: In this retrospective study we determined the results of salvage external beam radiation therapy (RT) to the prostate bed for isolated increase of serum prostate specific antigen (PSA) after radical prostatectomy., Materials and Methods: A total of 60 patients underwent RT for PSA failure after radical prostatectomy from 1993 to 1999. Median followup was 51 months. Biochemical disease-free survival (bDFS) with a serum PSA of 0.3 ng/ml or less was estimated using the Kaplan-Meier method. Potential prognostic factors were evaluated for significant associations with bDFS., Results: Median PSA before RT was 0.69 ng/ml. Median radiation dose was 64.8 Gy. The 5-year actuarial bDFS was 45%. There were 32 patients with a minimum followup of 4 years (median 73 months) who experienced a 5-year bDFS rate of 43%. PSA before RT (p = 0.016), RT dose (p = 0.026), surgical margin involvement (p = 0.017) and Gleason score (p = 0.018) were identified as prognostic factors for bDFS. A significant association with bDFS was present at 5 years of 65%, 34% and 0% for PSA before RT less than 0.6, 0.6 to 1.2, and greater than 1.2 ng/ml, respectively (p = 0.036). Patients with PSA before RT less than 0.6 ng/ml and total RT dose greater than 64.8 Gy had improved bDFS at 5 years compared to all others (77% vs 32%, p = 0.04). Of 60 patients 3 (5%) experienced chronic grade 3 toxicity., Conclusions: Optimal benefit from salvage RT was achieved in patients with a PSA less than 0.6 ng/ml and doses of RT greater than 64.8 Gy. Early treatment with a sufficiently high dose of RT maximizes the potential for salvage.