A risk-adjusted definition of biochemical recurrence after radical prostatectomy.

BACKGROUND: To determine whether a variable definition of biochemical recurrence (BCR) based on clincopathologic features facilitates early identification of patients likely to suffer from disease progression. The definition of BCR after radical prostatectomy (RP) bears important implications for patient counseling and management; however, there remains a significant debate regarding the appropriate definition. METHODS: The study cohort consisted of 3619 men who underwent RP for localized prostate cancer from 1989 to 2007, with data abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Patients were stratified into three risk groups according to Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score. Three single threshold PSA cut-points for BCR were evaluated (PSA > or =0.05, > or =0.2 and > or =0.4 ng ml(-1)) as well as a variable cut-point defined by risk group. After reaching the cut-points, patients were followed for further PSA progression. RESULTS: The proportion of patients with BCR differed by cut-point and risk group, ranging from 7 to 37% (low risk), 22 to 58% (intermediate risk) and 60 to 86% (high risk). The positive-predictive value (PPV) for predicting further PSA progression was 49% for the PSA > or =0.05 ng ml(-1), 62% for the PSA > or =0.2 ng ml(-1), 65% for the PSA > or =0.4 ng ml(-1) and 68% for the risk-adjusted definition. Five-year progression-free survival was 39% for the risk-adjusted definition compared with 45-52% for the other definitions of BCR. CONCLUSIONS: These data suggest that a variable definition of BCR determined by clinicopathologic risk may improve the identification of early recurrence after RP without increasing the overdiagnosis of BCR. By using a risk-adjusted BCR definition, clinicians can better predict future PSA progression and more appropriately counsel patients regarding salvage therapies.

Erectile dysfunction after radiotherapy for prostate cancer: a model assessing the conflicting literature on dose-volume effects.

Studies assessing the relationship between dose to the penile bulb (PB) and risk of ED in men treated for prostate cancer with external beam radiation therapy (EBRT) have been critically scored. A review of published literature examining dose received by the PB and clinical erectile function outcomes for patients receiving EBRT was performed. Of 146 retrieved articles, 8 evaluated EBRT-induced ED in relation to PB dose. Half of these articles showed a relationship between dose to PB and ED, and the other half did not. A reliability score (RS) was constructed to more uniformly evaluate strengths and weaknesses of these eight articles. Subsequently, they were scored by two independent reviewers. An average of both scores was calculated. A close consensus was found (identical RS for six of the eight studies; kappa statistic: P=0.97). The studies with highest RS consistently support a relationship between ED and PB doses, whereas those with low scores did not. The RS-based analysis supports the recommended dose-volume limits specified in the Quantitative Analysis of Normal Tissue Effects in the Clinic review, maintaining the mean dose to 95% of the PB<50 Gy, although the target organ at risk is not likely to be the PB.

Impact of dose hot spots on spinal cord tolerance following stereotactic body radiotherapy: a generalized biological effective dose analysis.

The purpose of this study was to investigate the effects of high-dose inhomogeneous irradiation to small volumes of spinal cord with a new generalized biological effective dose (gBED) analysis for spine stereotactic body radiotherapy (SBRT). The gBED was applied to spinal cord dosimetric data (contoured per the thecal sac) at specified volumes for a cohort of five patients with radiation-induced myelopathy (RM) and compared to nineteen patients without RM post-SBRT. The spinal cord gBED was calculated and normalized to a conventional 2-Gy equivalent dose fraction scheme (α/ß = 2 Gy for late toxicity). Differences between the conventional BED and those gBED calculations by accounting for small-volume dosing within the spinal cord was observed. Statistically significant differences in the mean gBED between the RM group and the non-RM group was observed both at the maximum point volume (gBED of 66 Gy vs. 37 Gy (p = 0.01), respectively) and at the 0.1 cm(3) volume (gBED of 53 Gy vs. 28 Gy (p = 0.01), respectively). No significant difference at the 0.1 cm(3) volume was observed based on the mean BED comparisons. No significant differences were observed at the larger 1 cm(3), 2 cm(3) or 5 cm(3) volumes for either BED or gBED comparisons. We conclude that differences in dose hot spots characteristics within small inhomogenously irradiated volumes of spinal cord can affect spinal cord tolerance following SBRT treatments.

Evolving immunosuppressive microenvironment during human cervical carcinogenesis.

Chronic infection with human papillomavirus (HPV) can result in cervical cancer. To understand how HPV escapes immune eradication, we examined biophenotypes of immune cells in human normal cervix, cervical intraepithelial neoplasia (CIN), and cancer. Expression and cellular localization of Forkhead box protein-3 (FOXP3), indolamine 2,3-dioxygenase (IDO), interleukin (IL)-10, and interferon (IFN)-gamma were examined by immunofluorescence and immunohistochemistry. Mean cell densities of stromal FOXP3+ cells, IDO+ cells, IL-10+ cells, CD1a+ cells, and macrophages significantly increased from normal cervix to cancer, whereas densities of IFN-gamma+ and MMP-9+ cells increased from normal cervix to CIN but decreased in cancer. Flow cytometry confirmed significant elevation of cervical T cells expressing IFN-gamma and transforming growth factor-beta in CIN compared with normal cervix. Upon activation, a significantly increased proportion of cervical T cells expressed IFN-gamma in CIN than normal. A unique subset of morphologically immature stromal dendritic cells expressing IL-10 and IDO was more numerous in cancer than in normal cervix and CIN. The potentially suppressive immune milieu in the cervix may be permissive of HPV-associated cervical carcinogenesis.

Beta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell lines.

AIMS: To investigate the cytotoxicity of beta-lapachone, a potent agent that may selectively target tumour cells, in retinoblastoma (RB) cell lines. METHODS: Growth inhibitory effects of beta-lapachone were evaluated in Y79, WERI-RB1, and RBM human retinoblastoma cell lines. Pro-apoptotic effects of beta-lapachone were evaluated in Y79 cells by detection of caspase 3/7 activity, by enzyme-linked immunosorbent assay for nucleosome fragments, and by cellular morphological analysis. RESULTS: Beta-lapachone induced significant dose-dependent growth inhibitory effects in all three retinoblastoma cell lines. The 50% growth inhibitory concentration (IC(50)) of this agent was 1.9 microM in Y79 cells, 1.3 microM in WERI-RB1 cells, and 0.9 microM in RBM cells. Beta-lapachone also induced proapoptotic effects in RB cells. Treatment of Y79 cells with 1.9 microM beta-lapachone (IC(50)) resulted in a peak, fourfold induction of caspase 3/7 activity at 72 h post-treatment; a peak, 5.6-fold increase in nucleosome fragments at 96 h post-treatment; and a peak, 1.7-fold increase in the frequency of apoptotic cells at 48 h post-treatment, relative to vehicle-treated controls. CONCLUSION: Beta-lapachone induced potent cytotoxic effects in RB cell lines at low micromolar concentrations, suggesting this agent could be useful in the clinical management of RB.

Defining high risk prostate cancer with risk groups and nomograms: implications for designing clinical trials.

PURPOSE: Death from prostate cancer is usually preceded by metastases and it usually occurs in men with high risk disease who experienced biochemical failure with a short prostate specific antigen doubling time. We developed a model for determining disease specific survival in prostate cancer. MATERIALS AND METHODS: We used the model for defining high risk prostate cancer that was developed by the Radiation Therapy Oncology Group and combined it with the Kattan nomogram for predicting the risk of metastases. We selected 414 Radiation Therapy Oncology Group intermediate and high risk patients who were treated with external beam radiotherapy alone. Excluded were patients with low risk disease. The Kaplan-Meier product limit method was used to estimate the probability of freedom from biochemical failure, overall survival and disease specific survival. RESULTS: A significant difference was observed in freedom from biochemical failure, disease specific survival and overall survival among the 3 tertiles created by the nomogram using the cutoff points less than 8.5%, 8.5% to 15% and greater than 15% (p <0.001, 0.0002 and 0.0003, respectively). Only the risk of metastases using the categorized nomogram score (less than 8.5% and 8.5% to 15% vs greater than 15%), not preradiotherapy prostate specific antigen or Radiation Therapy Oncology Group risk (Radiation Therapy Oncology Group 2 vs 3), was a significant predictor of disease specific and overall survival for intermediate/high risk patients and intermediate/high risk with 15% or less risk for metastases. CONCLUSIONS: We combined a risk group stratification scheme for disease specific survival with a nomogram predicting the risk of metastases and created a model that may be useful for designing phase III trials with metastases and disease specific survival as study end points.

Preliminary evaluation of prostate cancer metastatic risk biomarkers.

Prostate cancer patients at high risk of metastasis need to be identified as early as possible since metastasis is invariably fatal. Treatment could be tailored to risk. Recent array comparative genomic hybridization (aCGH) studies of primary and metastatic prostate tumors identified 39 BAC clones capable of detecting genomic signatures of metastasis. We termed these loci the genomic evaluators of metastatic CaP (GEMCaP). Risk assessments were made on a set of men who were managed with radical prostatectomy. We compared the utility of GEMCaP loci and the Kattan nomogram, a common risk assessment tool, in relation to biochemical outcome. This preliminary evaluation experiment suggests we can use aCGH to detect genomic signatures of metastasis in primary tumors with an accuracy of 78%. The classification accuracy for the Kattan nomogram was 75%. Therefore, validation of GEMCaP is warranted in a larger, appropriately designed cohort.

Discordance between beliefs and recommendations of gynecologic oncologists in ovarian cancer management.

PURPOSE: The purpose of this study was to determine how physician experts make decisions for clinical scenarios in ovarian cancer and describe a profile of factors reported to influence treatment decisions. METHODS: A questionnaire was sent to Full Members of the Society of Gynecologic Oncologists regarding surgery and chemotherapy for scenarios of primary and recurrent ovarian cancer. RESULTS: In a scenario of primary presentation, 94% of respondents chose a treatment of tumor resection over chemotherapy. Despite the preference for surgery in a clinical scenario, 50% agreed with a statement that neoadjuvant chemotherapy is equivalent to primary surgery. In a scenario of recurrent disease, a comparable number of respondents chose a treatment of secondary cytoreductive surgery (45%) versus direct retreatment with chemotherapy (49%). Those choosing surgery responded that they believed in extensive surgery to achieve optimal cytoreduction. Most (62%) respondents described themselves as collaborative in treatment planning, yet only 24% reported that patient preference strongly influences their decision making. CONCLUSIONS: Although a plan for primary cytoreduction is favored, in specific scenarios, views were divided for the role of neoadjuvant chemotherapy. For a recurrent disease scenario, support was divided between secondary cytoreductive surgery and direct retreatment with chemotherapy. Further clinical research is necessary to minimize the discordance between physician beliefs and recommendations.

Evaluation of ultrasound-based prostate localization for image-guided radiotherapy.

To evaluate the use of the ultrasound-based BAT system for daily prostate alignment. Prostate alignments using the BAT system were compared with alignments using radiographic images of implanted radiopaque markers. The latter alignments were used as a reference. The difference between the BAT and marker alignments represents the displacements that would remain if the alignments were done using ultrasonography. The inter-user variability of the contour alignment process was assessed. On the basis of the marker alignments, the initial displacement of the prostate in the AP, superoinferior, and lateral direction was -0.9 +/- 3.9, 0.1 +/- 3.9, and 0.2 +/- 3.4 mm respectively. The directed differences between the BAT and marker alignments in the respective directions were 0.2 +/- 3.7, 2.7 +/- 3.9, and 1.6 +/- 3.1 mm. The occurrence of displacements >/=5 mm was reduced by a factor of two in the AP direction after the BAT system was used. Among eight users, the average range of couch shifts due to contour alignment variability was 7, 7, and 5 mm in the antero-posterior (AP), superoinferior, and lateral direction, respectively. In our study, the BAT alignments were systematically different from the marker alignments in the superoinferior, and lateral directions. The remaining random variability of the prostate position after the ultrasound-based alignment was similar to the initial variability. However, the occurrence of displacements >/=5 mm was reduced in the AP direction. The inter-user variation of the contour alignment process was significant.

What does postradiotherapy PSA nadir tell us about freedom from PSA failure and progression-free survival in patients with low and intermediate-risk localized prostate cancer?

OBJECTIVES: To determine whether the post-external beam radiotherapy (RT) prostate-specific antigen nadir (nPSA) improves our ability to predict freedom from PSA failure, progression-free survival (PFS), and overall survival. Controversy regarding the importance of nPSA after external beam RT as a prognostic indicator for patients with localized prostate cancer has continued. METHODS: This analysis was based on the data from 748 patients with low and intermediate-risk localized prostate cancer treated with external beam RT alone. Patients were categorized by nPSA quartile groups with cutpoints of less than 0.3, 0.3 to less than 0.6, 0.6 to less than 1.2, and 1.2 ng/mL or greater. Both univariate and multivariate analyses were used to determine the significance of nPSA on PSA failure (American Society for Therapeutic Radiology Oncology consensus definition), PFS (death after PSA failure), and overall survival (death from any cause). RESULTS: Freedom from PSA failure was strongly associated with nadir quartile groups (P <0.0001). PFS was also significantly different statistically among nadir quartile groups (P = 0.02). No statistically significant difference was found in overall survival associated with nPSA at this point. CONCLUSIONS: nPSA is a strong independent predictor of freedom from PSA failure and PFS in patients with low and intermediate-risk localized prostate cancer treated with RT alone. Longer follow-up and larger patient numbers are required to confirm these observations.

Minichromosome maintenance protein 2 expression in prostate: characterization and association with outcome after therapy for cancer.

The minichromosome maintenance (MCM) proteins are highly conserved proteins essential for initiating and regulating eukaryotic DNA replication. Recent studies have demonstrated the potential use of MCM proteins as markers of proliferation. We characterized the pattern of Mcm 2 staining in benign and malignant prostate tissues and examined the role of Mcm 2 expression in disease-free survival after surgery in men with localized prostate cancer. Tumors from 92 patients who underwent radical prostatectomy for prostate cancer (median follow-up of 54 months) were examined for Mcm 2 expression by immunohistochemistry using a monoclonal antibody. Prostate tissue from five men without histopathological evidence of prostate cancer was also stained for Mcm 2. Mcm 2 expression was quantified by calculating a labeling index, and patients were grouped according to degree of staining. An analysis of the association between Mcm 2 expression with traditional clinicopathological characteristics of prostate cancer was carried out. A Cox proportional hazards analysis was performed to determine whether Mcm 2 staining was a significant independent predictor of disease-free survival. Mcm 2 expression is low (<2%) and limited to the basal cell layer in nonmalignant prostate glands. Mcm 2 expression is consistently increased in malignant glands and is significantly associated with disease-free survival in univariate (P = 0.002) and multivariate (P = 0.01) analyses. Patients with high Mcm 2 expression exhibited shorter disease-free survival. Mcm 2 expression was not associated with any traditional clinical or pathological factors and therefore is an independent predictor of survival in these patients with prostate cancer. These data support evidence that Mcm 2 may serve as a novel proliferation marker in the prostate. Mcm 2 expression is an independent predictor of disease-free survival after definitive local therapy and has potential as a molecular marker for clinical outcome in prostate cancer.

Is anastomotic biopsy necessary before radiotherapy after radical prostatectomy?

PURPOSE: External beam radiotherapy may be given after radical prostatectomy as adjuvant (immediate) or therapeutic (delayed) treatment, the latter in response to evidence of disease recurrence. In patients receiving delayed radiotherapy the necessity of a positive anastomotic biopsy before treatment remains unclear. We determined whether a positive anastomotic biopsy predicted the response to radiation in this setting. MATERIALS AND METHODS: We reviewed the records of 67 patients who received radiotherapy for biochemical or biopsy proved recurrent prostate cancer after radical prostatectomy. Patients underwent surgery at our institution or its affiliated hospitals, or were referred to our institution for radiotherapy. All patients had a negative metastatic evaluation before receiving radiotherapy. Biochemical failure after radiotherapy was defined as serum prostate specific antigen (PSA) 0.2 ng./dl. or greater on 2 or more consecutive occasions. Biochemical recurrence-free survival was calculated using the Kaplan-Meier method. Independent predictors of PSA failure after radiotherapy were identified using the multivariate Cox proportional hazards model. RESULTS: Of the 67 patients evaluated 33 and 34 received radiotherapy for biochemical failure and biopsy proved local recurrence, respectively. The 3-year recurrence-free survival rate was 49% in patients treated for biochemical failure and 39% in those with biopsy proved local recurrence. There was no significant difference in PSA-free survival in these 2 groups. Only pre-radiotherapy PSA 1 ng./dl. or greater (p = 0.02) and seminal vesicle invasion (p = 0.02) were significant independent predictors of biochemical failure. CONCLUSIONS: A positive anastomotic biopsy did not predict an improved outcome after radiotherapy following radical prostatectomy. Anastomotic biopsy was associated with a longer time to salvage radiotherapy. However, this delay did not translate into worse disease-free outcomes in patients who underwent anastomotic biopsy. High pre-radiotherapy PSA greater than 1 ng./ml. was the most significant predictor of biochemical failure after therapeutic radiotherapy. Decisions regarding local radiation therapy after radical prostatectomy may be made without documenting recurrent local disease.

Dose of radiation received by the bulb of the penis correlates with risk of impotence after three-dimensional conformal radiotherapy for prostate cancer.

OBJECTIVES: To evaluate the effect of the dose to the bulb of the penis on postradiation potency. METHODS: Twenty-one patients reporting potency before three-dimensional conformal radiotherapy had the dose delivered to the bulb of the penis evaluated. This was then compared with the patient assessments of post-treatment sexual function to determine whether a dose-volume relationship exists. RESULTS: Among the patients analyzed to date, a strong dose-volume relationship and the likelihood of remaining potent after treatment seems to exist. Patients receiving a dose of less than 40 Gy to 70% of the bulb of the penis appear to have a much greater likelihood of maintaining potency. Patients receiving 70 Gy or more to 70% of the bulb of the penis appear to be at very high risk of experiencing radiation-induced impotence (P = 0.03). CONCLUSIONS: More studies are needed to confirm these observations. If confirmed, these data suggest that by using three-dimensional-based treatment planning and carefully designed treatment fields, the potency of men treated with radiotherapy might be substantially improved.

Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing.

BACKGROUND & AIMS: The optimal strategy for the detection of hereditary nonpolyposis colorectal cancer (HNPCC) gene carriers remains uncertain. We evaluated whether microsatellite instability (MSI) analysis or MSH2 and MLH1 protein immunostaining of tumors will screen individuals efficiently for germline MSH2 and MLH1 testing. METHODS: We performed a case-series study of 114 eligible families enrolled in our high-risk colorectal cancer (CRC) registry. Medical history data were collected on probands and relatives. MSI analysis was performed on proband tumors, and MSH2 and MLH1 protein immunostaining was assessed. Denaturing gradient gel electrophoresis was used to identify germline MSH2 or MLH1 mutations in probands found to have tumors with high-frequency MSI. RESULTS: Tumor tissue and adequate clinical data were available in 109 of the 114 families. Amsterdam criteria and Bethesda guidelines were met by 23% and 70% of the families, respectively. High-frequency MSI was identified in the proband tumors in 47 of the 109 families (43%). Germline MSH2 and MLH1 gene testing was carried out in the probands of 32 of 47 families with MSI-H tumors. Mutations were detected in 16 families (9 in MSH2 and 7 in MLH1) and sequence variants of uncertain significance in 5 families (1 in MSH2 and 4 in MLH1). Germline mutations or sequence variants of uncertain significance were detected in 15 of 19 (79%) of our Amsterdam families and in 6 of 13 (46%) of our non-Amsterdam families with MSI-H tumors. MSH2 and MLH1 protein immunostaining was assessed in 38 of the 47 MSI-H tumors. Unequivocal loss of hMLH1 expression was found in 20 tumors and loss of MSH2 expression in 9 tumors. Corresponding loss of protein expression was seen in 17 of 18 (94%) of tumors from probands with germline mutations or variants. CONCLUSIONS: The detection of high-frequency MSI or the loss of MSH2 or MLH1 immunostaining in CRCs are both useful criteria for selecting high-risk patients who should be tested for germline mutations in MSH2 or MLH1.

Functional and clinical outcomes of limb-sparing therapy for pediatric extremity sarcomas.

PURPOSE: To determine the clinical and functional outcomes of children undergoing limb-sparing therapy for extremity sarcomas. METHODS AND MATERIALS: We retrospectively reviewed 30 patients, age < or = 21 years, who were treated between l979 and l998 with external beam radiotherapy as a component of limb-sparing therapy for primary sarcomas of the extremity at UCSF. Included were patients for whom complete follow-up and functional outcome assessments were available. We assessed the patterns of failure, overall survival, disease-free survival, local control, and limb function. RESULTS: At a median follow-up of 3 years, 12 of the 30 patients recurred: 3 locally, 8 distantly, and 1 with synchronous local and distant disease as site of first progression. Eighteen patients were alive with no evidence of disease. The median overall survival was 10 years, with a median disease-free survival of 8 years. Functional outcome assessment revealed 15 patients retained excellent, 12 good, 1 fair, and 2 poor limb function. CONCLUSION: In pediatric patients receiving limb-sparing therapy, 90% maintained excellent or good limb function without compromising survival, demonstrating the validity of limb preservation in children with extremity sarcomas.

Prostate volume change after radioactive seed implantation: possible benefit of improved dose volume histogram with perioperative steroid.

PURPOSE: To evaluate the changes in prostate volume associated with radioactive seed implantation and identify factors that influence prostate swelling. METHODS AND MATERIALS: Between June 1997 and August 1999, 161 patients implanted for prostate carcinoma at the University of California, San Francisco, had prostate volume measurements taken at 4 time points (preplan, preimplant, postimplant, postimplant dosimetry). Patient records were reviewed for treatment with perioperative steroids, hormone therapy (nHT), and external beam radiotherapy (EBRT). One and 2-way analysis of variance (ANOVA) methods were used to test differences in mean effects among patient subsets. RESULTS: A mean 20% volume increase was noted immediately postimplant overall (p < 0.0001), and even with EBRT and/or HT. Steroids were associated with a mean volume decrease of 19.9%, by 3-4 weeks post-procedure (p < 0.0001). Without steroids, only a 3.8% mean change was seen (p = ns). Steroid use resulted in a significant increase in mean dose-volume histogram (DVH) (p = 0.001); however, this benefit was only observed among patients who did not receive steroid. A consistently high DVH occurred with steroid use. CONCLUSION: A significant decrease in prostate volume and improved DVH are associated with steroid use. The diminished benefit of steroid use and higher mean DVH achieved in later years suggests the existence of a significant "learning curve" for brachytherapy procedures.

Hormonal evidence for altered responsiveness to social stress in major depression.

In patients with major depression, abnormalities in baseline cortisol secretion and resistance to negative feedback are well established. However, it is unclear if patients with major depression have alterations in the hypothalamic-pituitary-adrenal (HPA) response to stressors. While other challenges to the HPA axis have used endocrine stimuli such as insulin-induced hypoglycemia, we now report of the response to a social stressor in patients with major depression and matched control subjects. We used the Trier Social Stress Test (TSST), a public speaking task followed by mental arithmetic challenge in front of a panel of judges. The results suggest that depressed patients manifest normal cortisol response to a social stressor, despite increased pre-stressor plasma cortisol. However, the beta-endorphin response to the TSST was significantly smaller in the depressed patients compared to matched controls. These data are similar to data found with exogenous corticotropin-releasing-hormone challenge studies and suggest that elevated baseline cortisol can modulate the pituitary corticotroph response to a stressor, but that changes in adrenal sensitivity to ACTH result in a robust cortisol response to this stressor.

The impact of race on freedom from prostate-specific antigen failure in prostate cancer patients treated with definitive radiation therapy.

Many studies have reported that African-American men have the highest incidence and mortality rates for prostate cancer in the United States. A retrospective analysis of 607 patients treated with definitive radiation therapy was performed at the University of California San Francisco and its affiliated hospitals between 1987 and 1995. The patient population analyzed included African-American, Caucasian, and Asian men with AJCC T1-T3 disease. Race, Gleason score, pretreatment prostate-specific antigen levels, stage, and treatment delivery were all evaluated. The percent free from PSA failure at 48 months for African-American, Caucasian, and Asian men were 53%, 59%, and 53%, respectively. There was no difference among the three races or for any of the pairwise comparisons. Gleason score and stage of disease were each independent predictors of outcome, but race was not associated with remaining free from PSA failure. These results are similar to those recently reported in the literature from centers of excellence across the United States.

Management of a positive surgical margin after radical prostatectomy: decision analysis.

PURPOSE: We created and tested a decision analysis model to help determine the preferred management of a positive surgical margin(s) after radical prostatectomy. MATERIALS AND METHODS: We constructed a decision tree modeling surveillance versus immediate prophylactic adjuvant radiation in patients with a positive surgical margin(s) after radical prostatectomy. Literature and institution based estimates were determined for certain factors, including the probability of undetectable prostate specific antigen (PSA) in patients followed expectantly postoperatively and those treated with immediate adjuvant radiotherapy, complications of radiotherapy after prostatectomy and probability of undetectable PSA in those treated with therapeutic radiation for detectable PSA postoperatively. A panel of experts assigned utilities to the various outcomes. Sensitivity analysis was performed to determine threshold values required to change the model outcome. RESULTS: Using average probability estimates from a literature review the decision model recommended initial surveillance. Sensitivity analysis demonstrated that the model depended on the probability of disease recurrence in men followed expectantly after surgery as well as the efficacy of therapeutic radiation. We tested the decision model again for patient groups based on tumor grade, pathological stage, preoperative PSA and number of positive margins. The model recommended initial radiation for patients with low to intermediate grade disease, no evidence of seminal vesicle invasion and multiple positive margins. CONCLUSIONS: The results of our decision analysis imply that immediate radiation may be appropriate for patients with a positive surgical margin(s) and a high likelihood of recurrent local rather than distant disease. This model may be useful to physicians and patients who use individual probability estimates and utility values to determine the preferred course of management after surgery.