Advancing Traditional Prostate-specific Antigen Kinetics in the Detection of Prostate Cancer: A Machine Learning Model.

BACKGROUND: Prostate-specific antigen (PSA) kinetics, defined as the change in PSA over time, may be of use as a predictor of prostate cancer. PSA kinetics can be assessed as the PSA velocity, which is traditionally evaluated dichotomously and classified as abnormal if greater than either 0.35 or 0.75 ng/ml/yr. Machine learning models may provide additional benefit in assessing risk using PSA kinetics instead of PSA velocity. OBJECTIVE: To improve the utility of PSA kinetics by constructing a generalizable, universal machine learning model. DESIGN, SETTING, AND PARTICIPANTS: Data were obtained from the PLCO and PCPT trials and from a contemporary Australian cohort. PSA data were interpolated using a modified Gaussian process. A machine learning model based on a two-headed approach was designed, in which the multivariable input was fed into a one-dimensional ResNet18 model. OUTCOME MEASURES AND STATISTICAL ANALYSIS: The model performance was assessed compared to PSA levels and PSA velocity in terms of area under the receiver operator characteristic curve (AUC). RESULTS AND LIMITATIONS: A total of 10719 patients were included in the analysis. In tests on a validation set of the complete database to diagnose grade group ≥2, the AUC was 0.886 (95% confidence interval [CI] 0.870-0.902) for the machine learning model, compared to 0.807 (95% CI 0.796-0.819) for PSA and 0.627 (95% CI 0.607-0.648) for PSA velocity. CONCLUSIONS: Machine learning models can be used to augment the diagnostic utility of PSA kinetics in the diagnosis of prostate cancer. We demonstrated significant improvements in accuracy compared to the traditional approaches of PSA velocity and PSA thresholds. PATIENT SUMMARY: Prostate cancer diagnosis is limited by the diagnostic accuracy of the prostate-specific antigen (PSA) blood test. Advances in techniques such as machine learning algorithms can greatly improve the diagnostic accuracy of prostate cancer screening without additional costs or tests.

PSA-based machine learning model improves prostate cancer risk stratification in a screening population.

CONTEXT: The majority of prostate cancer diagnoses are facilitated by testing serum Prostate Specific Antigen (PSA) levels. Despite this, there are limitations to the diagnostic accuracy of PSA. Consideration of patient demographic factors and biochemical adjuncts to PSA may improve prostate cancer risk stratification. We aimed to develop a contemporary, accurate and cost-effective model based on objective measures to improve the accuracy of prostate cancer risk stratification. METHODS: Data were collated from a local institution and combined with patient data retrieved from the Prostate, Lung, Colorectal and Ovarian Cancer screening Trial (PLCO) database. Using a dataset of 4548 patients, a machine learning model was developed and trained using PSA, free-PSA, age and free-PSA to total PSA (FTR) ratio. RESULTS: The model was trained on a dataset involving 3638 patients and was then tested on a separate set of 910 patients. The model improved prediction for prostate cancer (AUC 0.72) compared to PSA alone (AUC 0.63), age (AUC 0.52), free-PSA (AUC 0.50) and FTR alone (AUC 0.65). When an operating point is chosen such that the sensitivity of the model is 80% the specificity of the model is 45.3%. The benefit in AUC secondary to the model was related to sample size, with AUC of 0.64 observed when a subset of the cohort was assessed. CONCLUSIONS: Development of a dense neural network model improved the diagnostic accuracy in screening for prostate cancer. These results demonstrate an additional utility of machine learning methods in prostate cancer risk stratification when using biochemical parameters.

CD169(+) macrophages mediate pathological formation of woven bone in skeletal lesions of prostate cancer.

Skeletal metastases present a major clinical challenge for prostate cancer patient care, inflicting distinctive mixed osteoblastic and osteolytic lesions that cause morbidity and refractory skeletal complications. Macrophages are abundant in bone and bone marrow and can influence both osteoblast and osteoclast function in physiology and pathology. Herein, we examined the role of macrophages in prostate cancer bone lesions, particularly the osteoblastic response. First, macrophage and lymphocyte distributions were qualitatively assessed in patient's prostate cancer skeletal lesions by immunohistochemistry. Second, macrophage functional contributions to prostate tumour growth in bone were explored using an immune-competent mouse model combined with two independent approaches to achieve in vivo macrophage depletion: liposome encapsulated clodronate that depletes phagocytic cells (including macrophages and osteoclasts); and targeted depletion of CD169(+) macrophages using a suicide gene knock-in model. Immunohistochemistry and histomorphometric analysis were performed to quantitatively assess cancer-induced bone changes. In human bone metastasis specimens, CD68(+) macrophages were consistently located within the tumour mass. Osteal macrophages (osteomacs) were associated with pathological woven bone within the metastatic lesions. In contrast, lymphocytes were inconsistently present in prostate cancer skeletal lesions and when detected, had varied distributions. In the immune-competent mouse model, CD169(+) macrophage ablation significantly inhibited prostate cancer-induced woven bone formation, suggesting that CD169(+) macrophages within pathological woven bone are integral to tumour-induced bone formation. In contrast, pan-phagocytic cell, but not targeted CD169(+) macrophage depletion resulted in increased tumour mass, indicating that CD169(-) macrophage subset(s) and/or osteoclasts influenced tumour growth. In summary, these observations indicate a prominent role for macrophages in prostate cancer bone metastasis that may be therapeutically targetable to reduce the negative skeletal impacts of this malignancy, including tumour-induced bone modelling. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A phase I clinical trial of CD1c (BDCA-1)+ dendritic cells pulsed with HLA-A*0201 peptides for immunotherapy of metastatic hormone refractory prostate cancer.

Preclinical studies have suggested that purified populations of CD1c (BDCA-1) blood-derived dendritic cells (BDC) loaded with tumor-specific peptides may be a feasible option for prostate cancer immunotherapy. We performed an open-label dose-finding Phase I study to evaluate the safe use of CD1c BDC in patients with advanced metastatic hormone refractory prostate cancer. HLA-A*0201-positive patients with advanced metastatic prostate cancer were recruited and consented. The vaccine was manufactured by pulsing autologous CD1c BDC, prepared by magnetic bead immunoselection from apheresed peripheral blood mononuclear cells, with a cocktail of HLA-A*0201-restricted peptides (prostate-specific antigen, prostate acid phosphatase, prostate specific membrane antigen, and control influenza peptide) and keyhole limpet hemocyanin. The vaccine was administered intradermally or intravenously and peripheral blood was taken at predetermined intervals for clinical and immunologic monitoring. The vaccine was manufactured with a median purity of 82% CD1c BDC and administered successfully to 12 patients. Each patient received between 1 and 5 × 10 fresh CD1c BDC on day 0, followed by cryopreserved product in the same dose on days 28 and 56. The vaccine was well tolerated in all patients, with the most frequent adverse events being grade 1-2 fever, pain, or injection-site reactions. Vaccination with CD1c BDC is therefore feasible, safe, and well tolerated in patients with advanced-stage metastatic prostate cancer.

Proton magnetic resonance spectroscopy of the central, transition and peripheral zones of the prostate: assignments and correlation with histopathology.

Proton magnetic resonance spectroscopy (MRS) is used to compare the chemistry of the transition, central and peripheral zones of the prostate. The assignments are made using two-dimensional correlated spectroscopy and the results compared with histopathology. The chemistry associated with benign prostatic hyperplasia (BPH), prostate intraepithelial neoplasia (PIN) and malignant biopsy tissues are described. There are distinct MR spectral patterns for glandular and stromal BPH, PIN and adenocarcinoma. Importantly, there are also different spectral patterns from BPH in the transitional and central zones when compared to BPH in the peripheral zone. A pattern recognition method is used to analyze the MR spectra from the biopsy specimens. The resultant mathematical classifiers generated a high level of accuracy (sensitivity and specificity of 100 and 97%). It was found that for this accuracy to be achieved, the classifiers need to be developed by comparing the spectra with specialist serial sectioned histopathology. With serial sectioned pathology the pattern recognition method was capable of identifying less than 5% of adenocarcinoma in a given piece of tissue. Many of the chemicals identified in the biopsy specimens are available for inspection from the prostate, in vivo, at 3 T.

Do margins matter? The prognostic significance of positive surgical margins in radical prostatectomy specimens.

PURPOSE: The prognostic significance of positive surgical margins (PSM) in radical prostatectomy (RP) specimens remains unclear. While most studies have concluded that a PSM is an independent adverse prognostic factor, others report that surgical margin status has no effect on prognosis. One reason for these discordant conclusions is the variable number of patients with a PSM who receive adjuvant therapy and the differing statistical methods used to account for the effects of the time course of adjuvant treatment on recurrence. We evaluated the prognostic significance of PSMs using multiple methods of analysis accounting for patients who received adjuvant therapy. MATERIALS AND METHODS: We analyzed 1,389 consecutive patients with clinical stage T1-3 prostate cancer treated with RP by 2 surgeons from 1983 to 2000. Of 179 patients with a PSM, 37 received adjuvant therapy (AT), 29 radiation therapy and 8 received hormonal therapy. Because the method used to account for men receiving AT can affect the outcome of the analysis, data were analyzed by the Cox proportional hazards technique accounting for patients receiving AT using 5 methods: 1) exclusion, 2) inclusion (AT ignored), 3) censoring at time of AT, 4) failing at time of AT and 5) considering AT as a time dependent covariate. RESULTS: Overall 179 patients (12.9%) had a PSM, including 6.8% of 847 patients with pT2 and 23% of 522 patients with pT3 disease. A PSM was a significant predictor of cancer recurrence when analyzed using methods 1, 3, 4 and 5 (p=0.005, p=0.014, p=0.0005, p=0.002, respectively). However, it was not a predictor of recurrence using method 2 in which AT was ignored (p=0.283). Using method 5 multivariate analysis demonstrated that a PSM (p=0.002) was an independent predictor of 10-year progression-free probability (PFP) along with Gleason score (p=0.0005), extracapsular extension (p=0.0005), seminal vesicle invasion (p <0.0005), positive lymph nodes (p <0.0005) and preoperative serum prostate specific antigen (p <0.0001). Using method 5 the 10-year PFP was 58% +/- 12% and 81% +/- 3% for patients with and without a PSM, respectively (p <0.00005). The relative risk of recurrence in men with a PSM using method 5 was 1.52 (95% confidence interval 1.06-2.16). CONCLUSIONS: We confirm that a PSM has a significant adverse impact on PFP after RP in multivariate analysis using multiple statistical methods to account for patients who received AT. While prostate cancer screening strategies have resulted in a majority of men having organ confined disease at RP, surgeons should continue to strive to reduce the rate of positive surgical margins to improve cancer control outcomes.

Laparoscopic radical prostatectomy for localized prostate cancer: a systematic review of comparative studies.

PURPOSE: We compared the safety and efficacy of laparoscopic and open radical prostatectomy through a systematic assessment of the literature. MATERIALS AND METHODS: Literature databases were searched from 1996 to December 2004 inclusive. Studies comparing transperitoneal laparoscopic radical prostatectomy, extraperitoneal endoscopic radical prostatectomy or robot assisted radical prostatectomy with open radical retropubic prostatectomy or radical perineal prostatectomy for localized prostate cancer were included. Comparisons between different laparoscopic approaches were also included. RESULTS: We identified 30 comparative studies, of which none were randomized controlled trials. There were 21 studies comparing laparoscopic with open prostatectomy with a total of 2,301 and 1,757 patients, respectively, and 9 comparing different laparoscopic approaches with a total of 1,148 patients. In terms of safety there did not appear to be any important differences in the complication rate between laparoscopic and open approaches. However, blood loss and transfusions were lower for laparoscopic approaches. In terms of efficacy operative time was longer for laparoscopic than for open prostatectomy but length of stay and duration of catheterization were shorter. Positive margin rates and recurrence-free survival were similar. Continence and potency were not well reported but they appeared similar for the 2 approaches. There were no important differences between laparoscopic approaches. CONCLUSIONS: Laparoscopic radical prostatectomy is emerging as an alternative to open radical prostatectomy but randomized, controlled trials considering patient relevant outcomes, such as survival, continence and potency, with sufficient followup are required to determine relative safety and efficacy.

Numerical and functional assessment of blood dendritic cells in prostate cancer patients.

BACKGROUND: Prostate cancer is one of the leading causes of cancer deaths in males and there are currently no effective treatments available for metastatic disease. Although recent clinical trials using dendritic cell (DC) based immunotherapy treatments have demonstrated safety, immunological responses, and some clinical efficacy, better vaccine delivery strategies need to be developed. We have undertaken the first detailed analysis of blood DC (BDC) subsets and their function in prostate cancer patients, with a view to utilizing immunoselected BDC for immunotherapy. METHODS: We enumerated the CD11c+CD1c+, CD11c+CD16+, and CD11c-CD123+ BDC subsets in whole blood of prostate cancer patients using a single platform TruCOUNT assay. These subsets were identified and purified using flow cytometry and immunomagnetic selection, and their functional capacity analyzed by costimulatory molecule expression, cytokine secretion, and antigen presenting ability. RESULTS: There were no significant differences in the number or composition of these subsets compared to healthy donors and these cells could be purified with equal efficiency from both groups. The prostate cancer patients BDC had similar levels of key costimulatory molecules and cytokine expression profiles, compared to healthy donors, and these were upregulated to the same extent, in response to exogenous stimuli. BDC from both groups were capable of eliciting allogeneic proliferative responses and inducing autologous CD4+ responses to naïve and recall antigens, and antigen-specific CD8+ responses to influenza matrix protein and prostate specific antigen. CONCLUSIONS: These results indicate that an immunoselected CD1c+ BDC preparation could provide a suitable vaccine delivery vehicle for future prostate cancer immunotherapy trials.

Do margins matter? The prognostic significance of positive surgical margins in radical prostatectomy specimens.

PURPOSE: The prognostic significance of positive surgical margins (PSM) in radical prostatectomy (RP) specimens remains unclear. While most studies have concluded that a PSM is an independent adverse prognostic factor, others report that surgical margin status has no effect on prognosis. One reason for these discordant conclusions is the variable number of patients with a PSM who receive adjuvant therapy and the differing statistical methods used to account for the effects of the time course of adjuvant treatment on recurrence. We evaluated the prognostic significance of PSMs using multiple methods of analysis accounting for patients who received adjuvant therapy. MATERIALS AND METHODS: We analyzed 1,389 consecutive patients with clinical stage T1-3 prostate cancer treated with RP by 2 surgeons from 1983 to 2000. Of 179 patients with a PSM, 37 received adjuvant therapy (AT), 29 radiation therapy and 8 received hormonal therapy. Because the method used to account for men receiving AT can affect the outcome of the analysis, data were analyzed by the Cox proportional hazards technique accounting for patients receiving AT using 5 methods: 1) exclusion, 2) inclusion (AT ignored), 3) censoring at time of AT, 4) failing at time of AT and 5) considering AT as a time dependent covariate. RESULTS: Overall 179 patients (12.9%) had a PSM, including 6.8% of 847 patients with pT2 and 23% of 522 patients with pT3 disease. A PSM was a significant predictor of cancer recurrence when analyzed using methods 1, 3, 4 and 5 (p=0.005, p=0.014, p=0.0005, p=0.002, respectively). However, it was not a predictor of recurrence using method 2 in which AT was ignored (p=0.283). Using method 5 multivariate analysis demonstrated that a PSM (p=0.002) was an independent predictor of 10-year progression-free probability (PFP) along with Gleason score (p=0.0005), extracapsular extension (p=0.0005), seminal vesicle invasion (p <0.0005), positive lymph nodes (p <0.0005) and preoperative serum prostate specific antigen (p <0.0001). Using method 5 the 10-year PFP was 58% +/- 12% and 81% +/- 3% for patients with and without a PSM, respectively (p <0.00005). The relative risk of recurrence in men with a PSM using method 5 was 1.52 (95% confidence interval 1.06-2.16). CONCLUSIONS: We confirm that a PSM has a significant adverse impact on PFP after RP in multivariate analysis using multiple statistical methods to account for patients who received AT. While prostate cancer screening strategies have resulted in a majority of men having organ confined disease at RP, surgeons should continue to strive to reduce the rate of positive surgical margins to improve cancer control outcomes.

Suspected local recurrence after radical prostatectomy: endorectal coil MR imaging.

PURPOSE: To evaluate endorectal coil magnetic resonance (MR) imaging in the depiction of local recurrence after radical prostatectomy. MATERIALS AND METHODS: Endorectal MR images were reviewed retrospectively in 82 patients who underwent prostatectomy. The interval between prostatectomy and MR imaging ranged between 0.5 and 13.0 years (mean, 3.25 years). Local recurrence was considered present if there was no evidence of distant metastases and there was a positive biopsy result, subsequent reduction in prostate-specific antigen (PSA) level after radiation therapy of the pelvis, or serial MR imaging findings of increased tumor size. Local recurrence on MR images was assessed for location, size, signal intensity, and invasion of adjacent structures. All images were reviewed independently by two readers who were blinded to clinical information. RESULTS: Thirty-four of 82 patients did not meet inclusion criteria. Forty-one of 48 remaining patients had clinically documented local recurrence, which MR imaging depicted in 39 of 41 (95%) patients. Seven of 48 patients had no evidence of local or distant metastases, and none had positive MR imaging findings. Sensitivity of MR imaging was 95%, and specificity was 100%. Local recurrences were perianastomotic in 12 (29%) patients and retrovesical in 17 (40%), within retained seminal vesicles in nine (22%), and at anterior or lateral surgical margins in four (9%). All local recurrences were hyperintense to adjacent pelvic muscles on T2-weighted MR images. The mean diameter of tumors was 1.4 cm (range, 0.8-4.5 cm). PSA levels at MR imaging in patients with clinically proved recurrences ranged from undetectable to 10 ng/mL (mean, 2.18 ng/mL). CONCLUSION: MR imaging depicts a high proportion of local recurrence after prostatectomy. The authors propose incorporation of endorectal coil MR imaging in the diagnostic paradigm of patients who have undergone prostatectomy and are suspected of having local recurrence.

Pathologic characterization of human prostate tissue with proton MR spectroscopy.

PURPOSE: To assess the accuracy of magnetic resonance (MR) spectroscopy in documenting the chemical features of human prostate tissue and to ascertain if there are chemical criteria of diagnostic importance. MATERIALS AND METHODS: Seventy-seven prostate tissue specimens (peripheral zone, n = 61; transitional zone, n = 16) from 43 patients were analyzed with MR spectroscopy. Histologic features were compared with MR spectroscopic data. Statistical analysis was undertaken with analysis of variance and computer software. RESULTS: Histologically identified carcinomas were determined by using MR spectroscopy with a sensitivity of 100% and a specificity of 94%. Histologically benign tissue from patients without carcinoma of the prostate was distinguished from malignant tissue with a sensitivity of 100% and a specificity of 94%. When benign specimens from patients with cancer elsewhere in the prostate were included in the database, MR spectroscopy helped distinguish benign prostatic hyperplasia from adenocarcinoma with a sensitivity of 97% and specificity of 88%. Depleted citrate and elevated choline levels alone were not accurate markers of malignancy, since citrate levels remain high when a small amount of malignant disease is present. Carcinomas missed at routine histologic examination were identified with MR spectroscopy and confirmed with specialized, nonstandard histologic examination. CONCLUSION: By comparing the intensity of resonances assigned to choline, creatine, lipid, and lysine, MR spectroscopy can depict prostate carcinoma with a high degree of sensitivity and specificity. Citrate and choline resonances alone are not sufficiently accurate markers for distinguishing between various patterns of prostatic disease.

Markers and meaning of primary treatment failure.

BCR is the most clinically used endpoint for identification of treatment failure. Approximately 15% to 53% of patients undergoing primary curative therapy will develop BCR. BCR often precedes clinically detectable recurrence by years. It does not necessarily translate directly into PCa morbidity and mortality, nor does it always reflect the desired endpoint. Furthermore, it has not been validated as a surrogate endpoint, in that interventions that have been shown to alter the PSA level have not been shown to also alter survival. The utility of PSA level as a surrogate endpoint is brought into question by the knowledge that the overall survival rate of patients at 10 years is similar in patients with and without BCR, and that in a significant proportion of men, the only evidence of disease during their lifetime will be a detectable PSA level. The likelihood of developing BCR post-therapy can be predicted by using multiple clinical and pathologic variables. With the development of nomograms that incorporate several markers, the accuracy of prediction has improved. Until recently, the natural history of BCR post-RRP has not been well understood. Pound et al showed the heterogenous and prolonged natural history of BCR. In this large series of men with BCR following RRP, only 34% of men developed metastatic disease. The median time from development of BCR to identification of metastases was 8 years, and the median time from the development of metastatic disease to death was just under 5 years. These data highlight the extremely variable and potentially indolent nature of BCR. The risk of metastatic disease following BCR has been relatively well defined and relates to PSADT and time to PSA recurrence. It generally is accepted that a PSADT of less than 6 to 10 months and a time to PSA recurrence of less than 1 to 2 years relates to a higher risk of developing metastatic disease. Local recurrence, however, remains poorly understood with respect to its true incidence, clinical significance, and natural history. The significance of BCR post-RT remains unclear due to the lack of data on its natural history. Attempts have been made to identify patients at high risk for metastatic progression by looking at time to PSA recurrence and PSADT. A PSADT of less than 6 to 12 months and a time to PSA recurrence of less than 12 months reflects a higher risk of developing metastatic disease. Accurate risk stratification by means of an algorithm similar to that produced by Pound et al has not been performed on a large cohort, thus making risk assessment for an individual patient difficult. The major dilemma for clinicians in the management of BCR is the identification of the site of disease recurrence, which ultimately guides therapy decisions. Clinicopathologic features allow for risk stratification for recurrence, and multiple investigations have attempted to localize the site of recurrence. Time to biochemical progression, Gleason score, and PSADT are predictive of the probability and time to development of metastatic disease, and allow for stratification of patients into different risk groups (see Table 2). TRUS, CT, PET, and DRE all have limited utility in the identification of local recurrence. ProstaScint and MRI have demonstrated encouraging initial results: however, they require further investigation. Bone scintigraphy is of little value for the initial investigation of BCR. In patients with a PSA level of less than 10 ng/mL, the risk of having a positive bone scan is less than 1% and, until the PSA level rises above 40 ng/mL, the risk of having a positive bone scan is less than 5%. Therefore, bone scintigraphy should be reserved for patients with a PSA level greater than 10 to 20 ng/mL or patients with a rapidly rising PSA level. Using new MRI sequences, there is some evidence that MRI is better for the detection of bony metastatic disease; however, this technique requires further investigation. BCR causes anxiety for the patient and the treating doctor, because the best way to manage patients with PSA-only progression is unknown. Currently, there are no validated treatment recommendations for the management of BCR. The information in this review provides the framework for assignment of patients into clinical trials based on different risk categories. Patients at high risk for metastatic progression could be identified early and thus entered into appropriate clinical trials for systemic therapies. Similarly, patients with a low risk of progression could be placed into observation protocols, potentially sparing them from exhaustive and inappropriate investigations.

National Comprehensive Cancer Network guidelines for the management of prostate cancer.

Guidelines for the management of prostate cancer issued by the National Comprehensive Cancer Network provide a basis for rational treatment decisions. These guidelines represent consensus recommendations by a panel of experts that are evidence based and are designated according to the degree of consensus within the expert panel. The initial stratification point is the patient's life expectancy (>5 or <5 years). If life expectancy is >5 years, the recommended intervention is based on clinical stage, prostate-specific antigen (PSA) level, and Gleason score, as well as the presence of symptoms. These assessments establish the patient's risk of recurrence after therapy. Specific initial therapies are then recommended according to whether the risk category is low, intermediate, high, or very high. The guidelines also describe the appropriate use of observation ("watchful waiting") versus active intervention in certain patients. After definitive therapy, patients should be monitored with PSA determinations, digital rectal examination, and bone scans, as outlined in the guidelines. Patients who exhibit increasing PSA levels after prostatectomy are candidates for salvage therapy with androgen ablation, radiotherapy, or observation. If PSA levels begin to increase after radiotherapy, surgery may then be an additional option. Systemic salvage therapy generally consists of androgen ablation; the benefit of total androgen blockade versus initial monotherapy remains controversial. Relapse after initial androgen ablation is treated with an antiandrogen, if none had been administered previously. Patients refractory to further hormonal manipulations are observed or receive palliative therapy, including chemotherapy. The treatment of prostate cancer is complex. Optimal treatment is risk-adapted to the specific characteristics of the cancer and the expected longevity and personal preferences of the patient.

Nomograms and instruments for the initial prostate evaluation: the ability to estimate the likelihood of identifying prostate cancer.

As a result of prostate cancer screening programs, approximately 10% of otherwise healthy men will be found to have an elevated prostate-specific antigen (PSA) level and therefore be at risk for harboring prostate cancer. Patients with an elevated PSA level have a wide variation in the risk for having prostate cancer diagnosed by transrectal ultrasound (TRUS)-guided prostate biopsy. To adequately counsel these patients, some form of individualized risk assessment must be given. There are several tables, artificial neural network (ANN) models, and nomograms that are available to stratify an individual patients risk for having prostate cancer diagnosed by a TRUS biopsy, either initially or on subsequent biopsies after a previous negative biopsy. Presently, nomograms are also being developed to predict the risk not only for having prostate cancer but also for clinically significant prostate cancer. The difficulty in calculating this risk for an individual patient is that the multiple competing clinical and pathologic factors have varying degrees of effect on the overall risk. This problem of competing risk factors can be overcome by the use of nomograms or ANNs. This article reviews the available instruments that are available to the urologist to enable prediction of the risk for having prostate cancer diagnosed by TRUS-guided prostate biopsy.