Determining optimal eluter design by modeling physical dose enhancement in brachytherapy.

PURPOSE: In situ drug release concurrent with radiation therapy has been proposed to enhance the therapeutic ratio of permanent prostate brachytherapy. Both brachytherapy sources and brachytherapy spacers have been proposed as potential eluters to release compounds, such as nanoparticles or chemotherapeutic agents. The relative effectiveness of the approaches has not been compared yet. This work models the physical dose enhancement of implantable eluters in conjunction with brachytherapy to determine which delivery mechanism provides greatest opportunity to enhance the therapeutic ratio. MATERIALS AND METHODS: The combined effect of implanted eluters and radioactive sources were modeled in a manner that allowed the comparison of the relative effectiveness of different types of implantable eluters over a range of parameters. Prostate geometry, source, and spacer positions were extracted from treatment plans used for 125 I permanent prostate implants. Compound concentrations were calculated using steady-state solution to the diffusion equation including an elimination term characterized by the diffusion-elimination modulus (ϕb ). Does enhancement was assumed to be dependent on compound concentration up to a saturation concentration (csat ). Equivalent uniform dose (EUD) was used as an objective to determine the optimal configuration of eluters for a range of diffusion-elimination moduli, concentrations, and number of eluters. The compound delivery vehicle that produced the greatest enhanced dose was tallied for points in parameter space mentioned to determine the conditions under whether there are situations where one approach is preferable to the other. RESULTS: The enhanced effect of implanted eluters was calculated for prostate volumes from 14 to 45 cm3 , ϕb from 0.01 to 4 mm-1 , csat from 0.05 to 7.5 times the steady-state compound concentration released from the surface of the eluter. The number of used eluters (ne ) was simulated from 10 to 60 eluters. For the region of (csat , Φ)-space that results in a large fraction of the gland being maximally sensitized, compound eluting spacers or sources produce equal increase in EUD. In the majority of the remaining (csat , Φ)-space, eluting spacers result in a greater EUD than sources even where sources often produce greater maximal physical dose enhancement. Placing eluting implants in planned locations throughout the prostate results in even greater enhancement than using only source or spacer locations. CONCLUSIONS: Eluting brachytherapy spacers offer an opportunity to increase EUD during the routine brachytherapy process. Incorporating additional needle placements permits compound eluting spacer placement independent of source placement and thereby allowing a further increase in the therapeutic ratio. Additional work is needed to understand the in vivo spatial distribution of compound around eluters, and to incorporate time dependence of both compound release and radiation dose.

The impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or with androgen deprivation therapy for unfavorable-risk prostate cancer.

BACKGROUND: The optimal management of men with PSA failure following initial prostate cancer (PC) therapy stratified by comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all-cause mortality (ACM), prostate cancer-specific mortality (PCSM) and other-cause mortality (OCM) following PSA failure. METHODS: Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT); 108 men experienced PSA failure and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM, respectively, stratified by comorbidity status using a validated metric. RESULTS: After a median follow-up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal (adjusted hazard ratio (AHR) 0.33, 95% confidence interval (CI) 0.17-0.65, P=0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, P=0.0002). However, because of the different contributions of the risk of OCM to risk of ACM within comorbidity subgroups, increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, P=0.03) but not moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, P=0.87). CONCLUSIONS: Both the extent of comorbidity and the PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure.

Duration of the anti-androgen in men undergoing 6 months of an LHRH agonist and radiation therapy for unfavorable-risk prostate cancer and the risk of death.

BACKGROUND: Whether adding a first-generation anti-androgen (AA) to a luteinizing hormone-releasing hormone agonist in the radiotherapeutic management of unfavorable-risk prostate cancer (PC) reduces the risk of all-cause and PC-specific mortality (ACM and PCSM) among men within differing comorbidity subgroups is unknown. METHODS: Between 1995 and 2001, 206 men with unfavorable-risk PC were enrolled in a randomized trial comparing radiation with or without 6 months of androgen-deprivation therapy (ADT). Partial AA use (median: 4.2 months) occurred in 29 of the 102 men randomized to ADT. Cox, and Fine and Gray's regressions were used to evaluate the impact of full versus partial AA use on PCSM and ACM-risk within comorbidity subgroups. RESULTS: After a median follow-up of 16.62 years, 156 men died. In men with moderate to severe comorbidity increasing death was observed as treatment transitioned from no to partial to full ADT (P=0.02) with an increased ACM-risk with full versus partial AA use (adjusted hazard ratio (AHR), 2.25 (95% confidence interval (CI), 0.94-5.41); P=0.07); whereas only 1 and no PC deaths occurred in men receiving a partial versus full AA course, respectively. Among men with no or minimal comorbidity there was no decrease in ACM (AHR, 0.97 (95% CI, 0.49-1.91); P=0.92) or PCSM-risk (AHR 0.39 (95% CI 0.07-52.18); P=0.28) in comparing full versus partial AA use. CONCLUSION: Increasing AA use by 2 months does not appear to impact survival in men with localized unfavorable-risk PC and no or minimal comorbidity, but may shorten survival in men with moderate to severe comorbidity, raising concern regarding in whom and for how long the AA should be prescribed.

Which, when and why? Rational use of tissue-based molecular testing in localized prostate cancer.

An increased molecular understanding of localized prostate cancer and the improved ability for molecular testing of pathologic tissue has led to the development of multiple clinical assays. Here we review the relevant molecular biology of localized prostate cancer, currently available tissue-based tests and describe which is best supported for use in various clinical scenarios. Literature regarding testing of human prostate cancer tissue with Ki-67, PTEN (by immunohistochemistry (IHC) or fluroescence in situ hybridization (FISH)), ProMark, Prolaris, OncotypeDX Prostate and Decipher was reviewed to allow for generation of expert opinions. At diagnosis, evaluation of PTEN status, use of ProMark or OncotypeDX Prostate in men with Gleason 6 or 3+4=7 disease may help guide the use of active surveillance. For men with Gleason 7 or above disease considering watchful waiting, Ki-67 and Prolaris add independent prognostic information. For those men who have undergone prostatectomy and have adverse pathology, Decipher testing may aid in the decision to undergo adjuvant radiation. Newly available molecular tests bring opportunities to improve decision making for men with localized prostate cancer. A review of the currently available data suggests clinical scenarios for which each of these tests may have the greatest utility.

High PSA anxiety and low health literacy skills: drivers of early use of salvage ADT among men with biochemically recurrent prostate cancer after radiotherapy?

BACKGROUND: Although commonly used, early initiation of salvage androgen deprivation therapy (ADT) has not been proven to enhance survival. We evaluated whether prostate-specific antigen (PSA) anxiety or health literacy are associated with use of early salvage ADT among men with recurrent prostate cancer after radiotherapy. PATIENTS AND METHODS: The prospective Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma Registry was used to study 375 men with biochemically recurrent prostate cancer after external beam radiation or brachytherapy. Multivariable logistic regression was used to determine whether PSA anxiety and health literacy are associated with salvage ADT as initial management after biochemical recurrence. RESULTS: Sixty-eight men (18.1%) received salvage ADT as initial management for PSA recurrence. Men with high PSA anxiety were twice as likely to receive salvage ADT compared with men who did not have high PSA anxiety on both univariable [28.8% versus 13.1%; odds ratio (OR) 2.15; 95% confidence interval (CI) 1.16-4.00; P = 0.015] and multivariable analysis [adjusted OR (AOR) 2.36; 95% CI 1.21-4.62; P = 0.012]. Furthermore, men who had higher levels of health literacy were nearly half as likely to undergo salvage ADT compared with men who had lower levels of health literacy on univariable analysis (15.2% versus 26.3%; OR 0.50; 95% CI 0.29-0.88; P = 0.016), with a trend toward this association on multivariable analysis (AOR 0.58; 95% CI 0.32-1.05; P = 0.07). CONCLUSIONS: Among men with PSA recurrence after radiotherapy, odds of use of salvage ADT were nearly twice as great among men with high PSA anxiety or low health literacy, suggesting that these men are receiving higher rates of unproven treatment. Given that early salvage ADT is costly, worsens quality of life, and has not been shown to improve survival, quality improvement strategies are needed for these individuals.

A refined risk stratification scheme for clinical stage 1 NSGCT based on evaluation of both embryonal predominance and lymphovascular invasion.

BACKGROUND: Active surveillance is an increasingly accepted approach for managing patients with germ-cell tumors (GCTs) after an orchiectomy. Here we investigate a time-to-relapse stratification scheme for clinical stage 1 (CS1) nonseminoma GCT (NSGCT) patients according to factors associated with relapse and identify a group of patients with a lower frequency and longer time-to-relapse who may require an alternative surveillance strategy. PATIENTS AND METHODS: We analyzed 266 CS1 GCT patients from the IRB-approved DFCI GCT database that exclusively underwent surveillance following orchiectomy from 1997 to 2013. We stratified NSGCT patients according to predominance of embryonal carcinoma (EmbP) and lymphovascular invasion (LVI), using a 0, 1, and 2 scoring system. Cox regression and conditional risk analysis were used to compare each NSGCT group to patients in the seminomatous germ-cell tumor (SGCT) category. Median time-to-relapse values were then calculated among those patients who underwent relapse. Relapse-free survival curves were generated using the Kaplan-Meier method. RESULTS: Fifty (37%) NSGCT and 20 (15%) SGCT patients relapsed. The median time-to-relapse was 11.5 versus 6.3 months for the SGCT and NSGCT groups, respectively. For NSGCT patients, relapse rates were higher and median time-to-relapse faster with increasing number of risk factors (RFs). Relapse rates (%) and median time-to-relapse (months) were 25%/8.5 months, 41%/6.8 months and 78%/3.8 months for RF0, RF1 and RF2, respectively. We found a statistically significant difference between SGCT and patients with one or two RFs (P < 0.001) but not between SGCT and NSGCT RF0 (P = 0.108). CONCLUSION: NSGCT patients grouped by a risk score system based on EmbP and LVI yielded three groups with distinct relapse patterns -and patients with neither EmbP nor LVI appear to behave similar to SGCT.

Incidence and determinants of 1-month mortality after cancer-directed surgery.

BACKGROUND: Death within 1 month of surgery is considered treatment related and serves as an important health care quality metric. We sought to identify the incidence of and factors associated with 1-month mortality after cancer-directed surgery. PATIENTS AND METHODS: We used the Surveillance, Epidemiology and End Results Program to study a cohort of 1 110 236 patients diagnosed from 2004 to 2011 with cancers that are among the 10 most common or most fatal who received cancer-directed surgery. Multivariable logistic regression analyses were used to identify factors associated with 1-month mortality after cancer-directed surgery. RESULTS: A total of 53 498 patients (4.8%) died within 1 month of cancer-directed surgery. Patients who were married, insured, or who had a top 50th percentile income or educational status had lower odds of 1-month mortality from cancer-directed surgery {[adjusted odds ratio (AOR) 0.80; 95% confidence interval (CI) 0.79-0.82; P < 0.001], (AOR 0.88; 95% CI 0.82-0.94; P < 0.001), (AOR 0.95; 95% CI 0.93-0.97; P < 0.001), and (AOR 0.98; 95% CI 0.96-0.99; P = 0.043), respectively}. Patients who were non-white minority, male, or older (per year increase), or who had advanced tumor stage 4 disease all had a higher risk of 1-month mortality after cancer-directed surgery, with AORs of 1.13 (95% CI 1.11-1.15), P < 0.001; 1.11 (95% CI 1.08-1.13), P < 0.001; 1.02 (95% 1.02-1.03), P < 0.001; and 1.89 (95% CI 1.82-1.95), P < 0.001 respectively. CONCLUSIONS: Unmarried, uninsured, non-white, male, older, less educated, and poorer patients were all at a significantly higher risk for death within 1 month of cancer-directed surgery. Efforts to reduce 1-month surgical mortality and eliminate sociodemographic disparities in this adverse outcome could significantly improve survival among patients with cancer.

The association between race and treatment regret among men with recurrent prostate cancer.

BACKGROUND: To examine the impact of race on treatment regret among men with recurrent prostate cancer after surgery or radiation. METHODS: The prospective Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma (COMPARE) registry was used to study a cohort of 484 men with biochemically recurrent prostate cancer after radical prostatectomy, external beam radiation or brachytherapy. Multivariable logistic regression was used to model the association between race and treatment regret and to determine whether there was an interaction between race and sexual problems after treatment with regards to treatment regret. RESULTS: Black men (N=78) were significantly more likely to have treatment regret when compared with non-black men (N=406; 21.8% versus 12.6%) on univariable analysis (odds ratio (OR) 1.94; 95% confidence interval 1.05-3.56; P=0.03). On multivariable analysis, black race trended towards but was no longer significantly associated with an increase in treatment regret (adjusted OR (AOR) 1.84 (0.95-3.58); P=0.071). There was an interaction between race and sexual problems after treatment (Pinteraction=0.02) such that among those without sexual problems, black men had more treatment regret than non-black men (26.7% versus 8.4%: AOR 4.68 (1.73-12.63); P=0.002), whereas among those with sexual problems, there was no difference in treatment regret between black and non-black men (18.8% versus 17.3%: AOR 1.04 (0.44-2.46); P=0.93). CONCLUSIONS: Among men with recurrent prostate cancer after surgery or radiation, black men were nearly twice as likely to experience treatment regret. Treating physicians should ensure that patients are fully apprised of the pros and cons of all treatment options to reduce the risk of subsequent regret.

The association between insurance status and prostate cancer outcomes: implications for the Affordable Care Act.

BACKGROUND: The Affordable Care Act (ACA) aims to expand health insurance coverage to over 30 million previously uninsured Americans. To help evaluate the potential impact of the ACA on prostate cancer care, we examined the associations between insurance coverage and prostate cancer outcomes among men <65 years old who are not yet eligible for Medicare. METHODS: The Surveillance, Epidemiology and End Results Program was used to identify 85 203 men aged <65 years diagnosed with prostate cancer from 2007 to 2010. Multivariable logistic regression modeled the association between insurance status and stage at presentation. Among men with high-risk disease, the associations between insurance status and receipt of definitive therapy, prostate cancer-specific mortality (PCSM) and all-cause mortality were determined using multivariable logistic, Fine and Gray competing-risks and Cox regression models, respectively. RESULTS: Uninsured patients were more likely to be non-white and come from regions of rural residence, lower median household income and lower education level (P<0.001 for all cases). Insured men were less likely to present with metastatic disease (adjusted odds ratio (AOR) 0.23; 95% confidence interval (CI) 0.20-0.27; P<0.001). Among men with high-risk disease, insured men were more likely to receive definitive treatment (AOR 2.29; 95% CI 1.81-2.89; P<0.001), and had decreased PCSM (adjusted hazard ratio 0.56; 95% CI 0.31-0.98; P=0.04) and all-cause mortality (adjusted hazard ratio 0.60; 0.39-0.91; P=0.01). CONCLUSIONS: Insured men with prostate cancer are less likely to present with metastatic disease, more likely to be treated if they develop high-risk disease and are more likely to survive their cancer, suggesting that expanding health coverage under the ACA may significantly improve outcomes for men with prostate cancer who are not yet eligible for Medicare.

Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer.

PURPOSE: To investigate the risk of postradiotherapy prostate-specific antigen (PSA) failure on the basis of pretreatment risk factors in prostate cancer patients with and without perineural invasion (PNI) in prostate biopsy specimens and to explain the observation that otherwise low-risk patients with PNI experience decreased freedom from PSA failure after external beam radiotherapy (RT). METHODS AND MATERIALS: The study cohort consisted of 381 patients who underwent RT between 1989 and 2000 for clinically localized prostate cancer. A single genitourinary pathologist scored the absence or presence of PNI on all prostate biopsy specimens. Patients were divided into low-, intermediate- and high-risk subgroups on the basis of their 1992 American Joint Committee on Cancer T-stage, pretreatment PSA level, and Gleason score. Cox regression uni- and multivariate analyses were performed to evaluate whether the presence or absence of PNI in the biopsy specimen was a predictor of the time to post-RT PSA failure for patients in each pretreatment risk group. PSA failure was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Actuarial PSA failure-free survival was estimated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. RESULTS: Cox regression univariate analysis revealed that PNI was a significant predictor of the time to PSA failure in the low-risk (p = 0.04) and high-risk (p = 0.03) cohorts. The 5-year PSA failure-free survival rate was 50% vs. 80% (p = 0.04) in low-risk patients, 70% vs. 75% (p = 0.72) in intermediate-risk patients, and 29% vs. 53% (p = 0.03) in high-risk patients with and without PNI, respectively. Cox regression multivariate analysis within the high-risk group revealed that a PSA level > or =20 ng/mL (p = 0.01) and Gleason score > or =8 (p = 0.02), but not PNI, were the only significant predictors of the time to PSA failure after RT. However, an association was found between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 8-10 (p = 0.06). The association was stronger between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 7-10 (p = 0. 033). CONCLUSION: A decrement in PSA outcome after RT for low-risk patients with PNI-positive biopsy specimens was found. The association between PNI and high Gleason score provides a possible explanation for the loss of statistical significance of PNI in the Cox regression multivariate analysis of the high-risk cohort. The data suggest that PNI found in the biopsy specimen of an otherwise low-risk patient predicts for occult high-grade disease that is missed owing to the sampling error associated with prostate biopsy. The association between PNI and a high Gleason score argues for the use of more aggressive therapy, such as hormonal therapy with RT and/or dose escalation, in these select patients.

A practical method to achieve prostate gland immobilization and target verification for daily treatment.

PURPOSE: A practical method to achieve prostate immobilization and daily target localization for external beam radiation treatment is described. METHODS AND MATERIALS: Ten patients who underwent prostate brachytherapy using permanent radioactive source placement were selected for study. To quantify prostate motion both with and without the presence of a specially designed inflatable intrarectal balloon, the computerized tomography-based coordinates of all intraprostatic radioactive sources were compared over 3 consecutive measurements at 1-min intervals. RESULTS: The placement and inflation of the intrarectal balloon were well tolerated by all patients. The mean (range) displacement of the prostate gland when the intrarectal balloon was present vs. absent was 1.3 (0-2.2) mm vs. 1.8 (0-9.1) mm (p = 0.03) at 2 min respectively. The maximum displacement in any direction (anterior-posterior, superior-inferior, or right-left) when the intrarectal balloon was inflated vs. absent was reduced to < or =1 mm from 4 mm. CONCLUSIONS: Both prostate gland immobilization and target verification are possible using a specially designed inflatable intrarectal balloon. Using this device, the posterior margin necessary on the lateral fields to ensure dosimetric coverage of the entire prostate gland could be safely reduced to 5 mm and treatment could be set up and verified using a lateral portal image.

Predicting prostate specific antigen outcome preoperatively in the prostate specific antigen era.

PURPOSE: We evaluated the ability of previously defined risk groups to predict prostate specific antigen (PSA) outcome 10 years after radical prostatectomy in patients diagnosed with clinically localized prostate cancer during the PSA era. MATERIALS AND METHODS: Between 1989 and 2000, 2,127 men with clinically localized prostate cancer underwent radical prostatectomy, including 1,027 at Hospital of the University of Pennsylvania (study cohort) and 1,100 at Brigham and Women's Hospital (validation cohort). Cox regression analysis was done to calculate the relative risk of PSA failure with the 95% confidence interval (CI) in patients at intermediate and high versus low risk. The Kaplan-Meier actuarial method was used to estimate PSA outcome 10 years after radical prostatectomy. RESULTS: Compared with low risk patients (stages T1c to 2a disease, PSA 10 ng./ml. or less and Gleason score 6 or less) the relative risk of PSA failure in those at intermediate (stage T2b disease or PSA greater than 10 to 20 ng./ml. or less, or Gleason score 7) and high (stage T2c disease, or PSA greater than 20 ng./ml. or Gleason score 8 or greater) risk was 3.8 (95% CI 2.6 to 5.7) and 9.6 (95% CI 6.6 to 13.9) in the study cohort, and 3.3 (95% CI 2.3 to 4.8) and 6.3 (95% CI 4.3 to 9.4) in the validation cohort. The 10-year PSA failure-free survival rate in the 1,020 patients in the low, 693 in the intermediate and 414 in the high risk groups was 83%, 46% and 29%, respectively (p <0.0001). CONCLUSIONS: Based on 10-year actuarial estimates of PSA outcome after radical prostatectomy 3 groups of patients were identified using preoperative PSA, biopsy Gleason score and 1992 clinical T category.

Combined-modality staging for localized adenocarcinoma of the prostate.

The goal of identifying a set of pretreatment risk-stratifying factors for patients with localized prostate cancer is to be able to individualize treatment and optimize patient selection for clinical trials. Low-risk patients are most likely to remain disease-free following local therapy, whereas high-risk patients are not. By identifying a high-risk group in which approximately two-thirds of the patients fail biochemically within 10 years following local therapy, the ability to detect a difference in outcome as a result of additional therapy (if any difference exists) is maximized. Specifically, small improvements in outcome associated with the use of novel therapies can be measured more quickly in the high-risk population because of the intrinsically higher failure and progression rates. Therefore, novel therapies should be studied first in high-risk populations using a prospective randomized trial design (ie, local therapy with or without novel therapy). If efficacy is established in the high-risk cohort, then testing could be considered in the low-risk population. This review will demonstrate the ability to risk stratify more than 90% of all patients with clinically localized prostate cancer into low- or high-risk groups for biochemical progression following local therapy using four readily available pretreatment clinical parameters.

Using the receiver operating characteristic curve to select pretreatment and pathologic predictors for early and late postprostatectomy PSA failure.

OBJECTIVES: Pretreatment prostate-specific antigen (PSA), prostatectomy Gleason score, margin status, and pathologic T stage are known explanatory variables for the postprostatectomy PSA outcome. We used the receiver operating characteristic (ROC) curve to select those factors that were optimal for predicting early and late postoperative PSA failure. METHODS: We designed and implemented a clinical outcome prediction expert that performs, assesses, and optimizes the actuarial prediction on individual cases. A postprostatectomy database of 1022 patients was divided into 60% for training and 40% for validation. The ROC areas of the predictors were calculated over a range of cutoff time from 24 to 60 months. RESULTS: Multivariate pathologic T stage/prostatectomy Gleason score/margin status had the highest ROC area of 0.900. Patients with Stage T disease less than T3, negative surgical margins, and Gleason score of 6 or less had a 90% probability to be PSA failure free at 4 years versus 36% otherwise. The pathologic T stage/margin status accurately predicted PSA failure at 24 months or less after prostatectomy with an ROC area of 0.800. Lower risk patients (less than Stage T3, negative surgical margins) had a 94% probability to be PSA failure free at 2 years versus 46% otherwise. CONCLUSIONS: A combination of actuarial analysis and ROC optimization accurately identified the individual patients at high risk of early and late postprostatectomy PSA failure.

Estimating the impact on prostate cancer mortality of incorporating prostate-specific antigen testing into screening.

OBJECTIVES: Whether early detection using prostate-specific antigen (PSA) and digital rectal examination (DRE) compared with DRE alone will reduce prostate cancer mortality awaits the results of ongoing prospective randomized trials. However, the impact that early detection could have on prostate cancer-specific survival can be estimated by assuming that PSA failure after radical prostatectomy (RP) will translate into death from prostate cancer. METHODS: The study population consisted of 1274 men with clinically localized prostate cancer who underwent RP in Boston, Massachusetts or Philadelphia, Pennsylvania between 1989 and 2000 and had a preoperative PSA level greater than 4 but not more than 10 ng/mL. The primary endpoint was actuarial freedom from PSA failure (defined as PSA outcome). RESULTS: The relative risk of PSA failure after RP for patients diagnosed with a PSA of greater than 4 to 5, 5 to 6, 6 to 7, or 7 to 8 ng/mL compared with greater than 8 up to 10 ng/mL was 0.3 (95% confidence interval [CI] 0.2 to 0.5), 0.5 (95% CI 0.4 to 0.8), 0.6 (95% CI 0.4 to 0.9), or 0.9 (95% CI 0.6 to 1.3), respectively. On the basis of the estimates of the 5-year PSA outcome, patients with a biopsy Gleason score of 5 or 6 (781 of 1274; 61%) consistently benefited from RP performed when the PSA at diagnosis was greater than 4 to 7 ng/mL compared with greater than 8 to 10 ng/mL (93% versus 78%, P <0.0001). A benefit to early detection was not found for the vast majority (266 of 312; 88%) of patients who had a biopsy Gleason score of 7 or higher. CONCLUSIONS: Early detection using both PSA and DRE-based screening may benefit men who present with biopsy Gleason score 5 or 6 prostate cancer and a PSA level greater than 4 to 7 ng/mL compared with greater than 8 up to 10 ng/mL. This finding awaits validation from ongoing prospective randomized trials.

MR imaging-guided prostate biopsy with surgical navigation software: device validation and feasibility.

Magnetic resonance (MR) imaging--guided prostate biopsy in a 0.5-T open imager is described, validated in phantom studies, and performed in two patients. The needles are guided by using fast gradient-recalled echo and T2-weighted fast spin-echo images. Surgical navigation software provided T2-weighted images critical to targeting the peripheral zone and the tumor. MR imaging can be used to guide prostate biopsy.

ROC optimization may improve risk stratification of prostate cancer patients.

OBJECTIVES: Rational treatment decision requires accurate projection of the clinical course of a patient. Current methods in clinical outcome analysis mostly focus on population data. We investigated the applicability and optimization of the widely used actuarial method to project individual clinical outcomes. METHODS: We designed and implemented a Clinical Outcome Prediction Expert (COPE) that performs, assesses, and optimizes actuarial prediction on individual cases. We analyzed a post-prostatectomy database, consisting of 1043 patients. Sixty percent of the database was used for training and 40% for validation. Stratified actuarial curves are used to project individual outcomes. The prostate-specific antigen (PSA) level, the Gleason score, and the clinical American Joint Commission on Cancer Staging T-stage before treatment were used as predictors. The area under the receiver operator characteristic (ROC) curve was used to measure predictive performance. RESULTS: We obtained simple optimized stratification of pretreatment PSA level of 10 ng/mL or less, or more than 10 ng/mL; Gleason score of 6 or lower, or higher than 6; and clinical AJCC T-stage of T2a or lower, or higher. The optimized univariate risk scores were used to generate a multivariate score. After optimization, we found the higher risk group consisted of patients with PSA more than 10 ng/mL, or with PSA of 10 ng/mL or less and Gleason score higher than 6 and clinical AJCC T-stage higher than T2a. The optimized multivariate risk score has the highest ROC area of 0.77 among all predictors. CONCLUSIONS: The best conditions to perform actuarial prediction on individual cases are not known a priori and require optimization. This study shows that ROC optimization simplifies risk stratification and may improve the accuracy of clinical outcome prediction.