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Purpose: Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services., Methods: A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider)., Results: Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM , for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM , and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches., Conclusion: This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

Background: Genomic classifiers (GC) have been shown to improve risk stratification post prostatectomy. However, their clinical benefit has not been prospectively demonstrated. We sought to determine the impact of GC testing on postoperative management in men with prostate cancer post prostatectomy., Methods: Two prospective registries of prostate cancer patients treated between 2014 and 2019 were included. All men underwent Decipher tumor testing for adverse features post prostatectomy (Decipher Biosciences, San Diego, CA). The clinical utility cohort, which measured the change in treatment decision-making, captured pre- and postgenomic treatment recommendations from urologists across diverse practice settings (n = 3455). The clinical benefit cohort, which examined the difference in outcome, was from a single academic institution whose tumor board predefined "best practices" based on GC results (n = 135)., Results: In the clinical utility cohort, providers' recommendations pregenomic testing were primarily observation (69%). GC testing changed recommendations for 39% of patients, translating to a number needed to test of 3 to change one treatment decision. In the clinical benefit cohort, 61% of patients had genomic high-risk tumors; those who received the recommended adjuvant radiation therapy (ART) had 2-year PSA recurrence of 3 vs. 25% for those who did not (HR 0.1 [95% CI 0.0-0.6], p = 0.013). For the genomic low/intermediate-risk patients, 93% followed recommendations for observation, with similar 2-year PSA recurrence rates compared with those who received ART (p = 0.93)., Conclusions: The use of GC substantially altered treatment decision-making, with a number needed to test of only 3. Implementing best practices to routinely recommend ART for genomic-high patients led to larger than expected improvements in early biochemical endpoints, without jeopardizing outcomes for genomic-low/intermediate-risk patients.

Purpose: High dose-rate (HDR) brachytherapy is commonly administered as a boost to external beam radiation therapy (EBRT). Our purpose was to compare toxicity with increasingly hypofractionated EBRT in combination with a single 15 Gy HDR boost for men with intermediate-risk prostate cancer., Methods and Materials: Forty-two men were enrolled on this phase IB clinical trial to one of three EBRT dose cohorts: 10 fractions, seven fractions, or five fractions. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition., Results: With a median follow up of 36 months, the biochemical disease-free survival was 95.5%. One man developed metastatic disease at 5 years. There was no significant minimally important difference in EPIC PRO for either urinary, bowel, or sexual domains. There was one acute Grade 3 GI and GU toxicity, but no late Grade 3 GU or GI toxicities., Conclusion: Fifteen gray HDR brachytherapy followed by a five fraction SBRT approach results in high disease control rates and low toxicity similar to previously reported HDR protocols with significant improvement in patient convenience and resource savings. While mature results with longer follow up are awaited, this treatment approach may be considered a safe and effective option for men with intermediate-risk disease., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Although current Delphi Consensus guidelines do not recommend a specific definition of biochemical recurrence after partial gland therapy, these guidelines acknowledge that serial prostate-specific antigen (PSA) tests remain the best marker for monitoring disease after treatment. The purpose of this study was to determine whether PSA velocity at failure per the Phoenix (nadir + 2 ng/mL) definition is associated with metastasis and prostate cancer-specific mortality (PCSM) in a cohort of patients who experienced PSA failure after partial gland therapy., Methods: Between 1997 and 2007, 285 patients with favorable risk prostate cancer underwent partial prostate brachytherapy to the peripheral zone. PSA velocity was calculated for 94 patients who experienced PSA failure per the Phoenix (nadir + 2) definition. Fine and Gray competing risks regression was performed to determine whether PSA velocity and other clinical factors were associated with metastasis and PCSM., Results: The median time to PSA failure was 4.2 years (interquartile range: 2.2, 7.9), and the median followup time after PSA failure was 6.5 years (3.5-9.7). Seventeen patients developed metastases, and five experienced PCSM. On multivariate analysis, PSA velocity ≥3.0 ng/mL/year (adjusted hazard ratio 5.97; [2.57, 13.90]; p < 0.001) and PSA nadir (adjusted hazard ratio 0.39; [0.24, 0.64]; p < 0.001) were significantly associated with metastasis. PSA velocity ≥3.0 ng/mL/year was also associated with PCSM (HR 15.3; [1.8, 128.0]; p = 0.012) on univariate analysis., Conclusions: Rapid PSA velocity at PSA failure after partial gland treatment may be prognostic for long-term outcomes., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Partial prostate treatment has emerged as a potential method for treating patients with favorable-risk prostate cancer while minimizing toxicity. The authors previously demonstrated poor rates of biochemical disease control for patients with National Comprehensive Cancer Network (NCCN) intermediate-risk disease using partial gland treatment with brachytherapy. The objective of the current study was to estimate the rates of distant metastasis and prostate cancer-specific mortality (PCSM) for this cohort., Methods: Between 1997 and 2007, a total of 354 men with clinical T1c disease, a prostate-specific antigen (PSA) level < 15 ng/mL, and Gleason grade ≤3 + 4 prostate cancer underwent partial prostate treatment with brachytherapy to the peripheral zone under 0.5-Tesla magnetic resonance guidance. The cumulative incidences of metastasis and PCSM for the NCCN very low-risk, low-risk, and intermediate-risk groups were estimated. Fine and Gray competing risk regression was used to evaluate clinical factors associated with time to metastasis., Results: A total of 22 patients developed metastases at a median of 11.0 years (interquartile range, 6.9-13.9 years). The 12-year metastasis rates for patients with very low-risk, low-risk, and intermediate-risk disease were 0.8% (95% confidence interval [95% CI], 0.1%-4.4%), 8.7% (95% CI, 3.4%-17.2%), and 15.7% (95% CI, 5.7%-30.2%), respectively, and the 12-year PCSM estimates were 1.6% (95% CI, 0.1%-7.6%), 1.4% (95% CI, 0.1%-6.8%), and 8.2% (95% CI, 1.9%-20.7%), respectively. On multivariate analysis, NCCN risk category (low risk: hazard ratio, 6.34 [95% CI, 1.18-34.06; P = .03] and intermediate risk: hazard ratio, 6.98 [95% CI, 1.23-39.73; P = .03]) was found to be significantly associated with the time to metastasis., Conclusions: Partial prostate treatment with brachytherapy may be associated with higher rates of distant metastasis and PCSM for patients with intermediate-risk disease after long-term follow-up. Treatment of less than the full gland may not be appropriate for this cohort., (© 2018 American Cancer Society.)

Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.

This study aimed to explore the effects of a decision support intervention (DSI) and shared decision making (SDM) on knowledge, perceptions about treatment, and treatment choice among men diagnosed with localized low-risk prostate cancer (PCa). At a multidisciplinary clinic visit, 30 consenting men with localized low-risk PCa completed a baseline survey, had a nurse-mediated online DS session to clarify preference for active surveillance (AS) or active treatment (AT), and met with clinicians for SDM. Participants also completed a follow-up survey at 30 days. We assessed change in treatment knowledge, decisional conflict, and perceptions and identified predictors of AS. At follow-up, participants exhibited increased knowledge (p < 0.001), decreased decisional conflict (p < 0.001), and more favorable perceptions of AS (p = 0.001). Furthermore, 25 of the 30 participants (83 %) initiated AS. Increased family and clinician support predicted this choice (p < 0.001). DSI/SDM prepared patients to make an informed decision. Perceived support of the decision facilitated patient choice of AS.

Background: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined., Methods: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The primary objective was to assess whether the addition of ADT and docetaxel to ART resulted in a freedom from progression (FFP) rate ≥ 70% compared with an expected rate of 50%. Multivariate logistic and Cox regression analyses were used to model associations between factors and outcomes., Results: In total, 74 patients were enrolled. The median follow-up was 4.4 years. The pathologic tumor classification was pT2 in 4% of patients, pT3 in 95%, and pT4 in 1%. The Gleason score was 7 in 18% of patients and ≥8 in 82%. Post-RP PSA levels were ≤0.2 ng/mL in 53% of patients and >0.2 ng/mL in 47%. The 3-year FFP rate was 73% (95% confidence interval, 61%-83%), and the 3-year cumulative incidence of biochemical, distant, and local failure was 26%, 7%, and 0%, respectively. In multivariate models, postprostatectomy PSA nadir was associated with 3-year FFP, Gleason score, and PSA with biochemical failure. Grade 3 and 4 neutropenia was common; however, only 3 episodes of febrile neutropenia occurred. Late toxicities were not impacted by the addition of systemic therapy., Conclusions: Combined ADT, docetaxel, and ART for men with high-risk prostate cancer after prostatectomy exceeded the prespecified study endpoint of 70% 3-year FFP. Phase 3 trials assessing combined local and systemic therapies for these high-risk patients are warranted. Cancer 2017;123:2489-96. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: We sought to determine whether patients with high-volume, low-risk prostate cancer are suitable candidates for ultrasound-guided brachytherapy, monotherapy alone, without supplemental external beam radiation., Materials and Methods: The study cohort comprised 200 consecutive patients who received ultrasound.guided monotherapy from November 02, 1998 to March 26, 2010. Real.time intraoperative treatment planning was performed for all patients. 145. Gy with I125 was prescribed to the prostate with no margin. The primary endpoint was time to prostate-specific antigen. (PSA) failure using the phoenix definition. Cox multivariable regression analysis was used to determine the factors significantly associated with time to PSA failure., Results: Median follow-up was 59 months (range 1.2-146.8 months). The median PSA was 5.0 ng/ml. For the overall cohort, both 5- and 8-year PSA failure-free survival was 92.3% (95% confidence interval [95% CI]: 86.5-95.7%). Low-risk patients per the NCCN criteria had 5- and 8-year PSA failure-free survival of 93.6%. On cox multivariable analysis, only baseline PSA (adjusted hazard ratio: 1.29 [95% CI: 1.02-1.65], P = 0.036) was associated with outcome. Among patients with Conclusions: Our analysis indicates that patients with a high number of cores positive for cancer can be adequately treated with modern brachytherapy as monotherapy and be spared the additional morbidity and cost of supplemental external beam radiation or androgen deprivation therapy.

Purpose: To determine if increasing the biologically equivalent dose (BED) via various radiation fractionation regimens is correlated with clinical outcomes or toxicities for prostate cancer., Methods and Materials: We performed a meta-analysis that included 12,756 prostate cancer patients from 55 studies published from 2003 to 2013 who were treated with non-dose-escalated conventionally fractionated external beam radiation therapy (non-DE-CFRT), DE-CFRT, hypofractionated RT, and high dose rate brachytherapy (HDR-BT; either mono or boost) with ⩾5-year actuarial follow-up. BEDs were calculated based on the following formula: (nd[1+d/(α/β)]), where n is the number of fractions, and d is dose per fraction; assuming an α/β of 1.5 for prostate cancer and 3.0 for late toxicities. Mixed effects meta-regression models were used to estimate weighted linear relationships between BED and the observed percentages of patients experiencing late toxicities or 5-year freedom from biochemical failure (FFBF)., Results: Increases in 10 Gy increments in BED (at α/β of 1.5) from 140 to 200 Gy were associated with 5-unit improvements in percent FFBF. Dose escalation of BED above 200 Gy was not correlated with FFBF. Increasing BED (at α/β of 3.0) from 98 to 133 Gy was associated with increased gastrointestinal toxicity. Dose escalation above 133 Gy was not correlated with toxicity., Conclusions: An increase in the BED to 200 Gy (at α/β of 1.5) was associated with increased disease control. Doses above 200 Gy did not result in additional clinical benefit., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

High-dose rate brachytherapy (HDR-BT) monotherapy and robotic arm (i.e., CyberKnife) stereotactic body radiation therapy (SBRT) are emerging technologies that have become popular treatment options for prostate cancer. Proponents of both HDR-BT monotherapy and robotic arm SBRT claim that these modalities are as efficacious as intensity-modulated radiation therapy in treating prostate cancer. Moreover, proponents of robotic arm SBRT believe it is more effective than HDR-BT monotherapy because SBRT is non-invasive, touting it as 'virtual HDR-BT.' We perform a comparative effective analysis of the two technologies. The tumor control rates and toxicities of HDR-BT monotherapy and robotic arm SBRT are promising. However, at present, it would be inappropriate to state that HDR-BT monotherapy and robotic arm SBRT are as efficacious or effective as other treatment modalities for prostate cancer, which have stronger foundations of evidence. Studies reporting on these technologies have relatively short follow-up time, few patients and are largely retrospective.

Purpose: Prostate volume greater than 50cc is traditionally a relative contraindication to prostate seed implantation (PSI), but there is little consensus regarding prostate size and clinical outcomes. We report biochemical control and toxicity after low-dose-rate PSI and compare outcomes according to the prostate size., Methods and Materials: A total of 429 men who underwent low-dose-rate PSI between 1998 and 2009 were evaluated. Median followup was 38.7 months. Patients were classified by prostate volume into small, medium, and large subgroups. Differences were analyzed using the Mann-Whitney and Pearson's χ(2) tests for continuous and categorical variables, respectively. Cox proportional hazards regression models were used to evaluate effect of prostate size on outcomes., Results: Patient pretreatment factors were balanced between groups except for age (p=0.001). The 10-year actuarial freedom from biochemical failure for all patients treated with PSI was 96.3% with no statistically significant difference between large vs. small/medium prostate size (90% vs. 96.6%, p=0.47). In a multivariate analysis, plan type (hazard ratio [HR]=0.25, p=0.03), dose to 90% of the gland (D90: HR=0.98, p=0.02), volume receiving 200Gy (V200: HR=0.98, p=0.026), and biologic effective dose (HR=0.99, p=0.045), but not prostate size (HR=2.27, p=0.17) were significantly associated with freedom from biochemical failure. Prostate size was not significantly associated with time to maximum American Urologic Association score., Conclusion: In men with large prostates, the PSI provides biochemical control and temporal changes in genitourinary toxicity that are comparable with men having smaller glands. Accurate dose optimization and delivery of PSI provides the best clinical outcomes regardless of gland size., (Published by Elsevier Inc.)

Studies of dose-escalated external beam radiation therapy (EBRT) and low dose rate brachytherapy (LDR-BT) have shown excellent rates of tumor control and cancer specific survival. Moreover, LDR-BT combined with EBRT (i.e. "LDR-BT boost") is hypothesized to improve local control. While phase II trials with LDR-BT boost have produced mature data of outcomes and toxicities, high dose rate (HDR)-BT has been growing in popularity as an alternative boost therapy. Boost from HDR-BT has theoretical advantages over LDR-BT, including improved cancer cell death and better dose distribution from customization of catheter dwell times, locations, and inverse dose optimization. Freedom from biochemical failure rates at five years for low-, intermediate-, high-risk, and locally advanced patients have generally been 85-100%, 80-98%, 59-96%, and 34-85%, respectively. Late Radiation Therapy Oncology Group grade 3-4 toxicities have also been encouraging with <6% of patients experiencing any toxicity. Limitations of current HDR-BT boost studies include reports of only single-institution experiences, and unrefined reports of toxicity or patient quality of life. Comparative effectiveness research will help guide clinicians in selecting the most appropriate treatment option for individual patients based on risk-stratification, expected outcomes, toxicities, quality of life, and cost., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Approximately a third of men with localized prostate cancer who are treated with external beam radiation therapy (EBRT) or radical prostatectomy (RP) develop biochemical failure (BF). Presumably, BF will progress to distant metastasis and prostate cancer-specific mortality in some patients over subsequent years. Accurate detection of recurrent disease is important because it allows for appropriate treatment selection (e.g., local vs systemic therapy) and early delivery of therapy (e.g., salvage EBRT), which affect patient outcome. In this article, we discuss the paradigm shift in imaging technology in the detection of recurrent prostate cancer. First, we discuss the commonly used morphological and anatomical imaging modalities and their role in the post-RP and post-EBRT settings of BF. Second, we discuss the accuracy of functional and molecular imaging techniques, many of which are under investigation. Further studies are needed to establish the role of imaging techniques for detection of cancer recurrence and clinical decision-making.

Low-dose rate brachytherapy (LDR-BT), involving implantation of radioactive seeds into the prostate, is an established monotherapy for most low-risk and select intermediate- and high-risk prostate cancer patients. High-dose rate brachytherapy (HDR-BT) is an advanced technology theorized to be more advantageous than LDR-BT from a radiobiological and radiophysics perspective, to the patient himself, and in terms of resource allocation. Studies of HDR-BT monotherapy have encouraging results in terms of biochemical control, patient survival, treatment toxicity and erectile preservation. However, there are still certain limitations that preclude recommending HDR-BT monotherapy for prostate cancer outside the setting of a clinical trial. HDR-BT monotherapy should be considered experimental at present.

External beam radiation therapy (EBRT) combined with brachytherapy (BT) is an attractive treatment option for select patients with clinically localized prostate cancer. Either low- or high-dose rate BT may be combined with EBRT ('LDR-BT boost,' 'HDR-BT boost,' respectively). HDR-BT boost has potential theoretical benefits over LDR-BT boost or external beam radiation therapy monotherapy in terms of radiobiology, radiophysics and patient convenience. Based on prospective studies in this review, freedom from biochemical failure (FFBF) rates at 5 years for low-, intermediate- and high-risk patients have generally been 85-100%, 68-97%, 63-85%, respectively; late Radiotherapy and Oncology Group Grades 3 and 4 genitourinary and gastrointestinal toxicities are seen in <8% of patients. HDR-BT boost is now a relatively well-established treatment modality for certain intermediate-risk and high-risk prostate cancer patients, though limitations exist in drawing conclusions from the currently published studies.

Conventional treatment options for clinically localized, low-risk prostate cancer include radical prostatectomy, external-beam radiotherapy (EBRT) and low-dose-rate brachytherapy. Advances in image-guided radiotherapy (IGRT) since the 1980s, the development of intensity-modulated radiotherapy (IMRT) during the 1990s and evidence from radiobiological models--which support the use of high doses per fraction--have developed alongside novel advanced radiotherapy modalities that include high-dose-rate brachytherapy (HDR-BT), stereotactic body radiotherapy (SBRT) and proton beam therapy. The relationship between the outcomes of and toxicities experienced by patients with prostate cancer treated with HDR-BT, SBRT and particle-beam therapy should provide urologists and oncologists an understanding of the continually evolving technology in prostate radiotherapy. On the basis of published evidence, conventionally fractionated EBRT with IMRT is considered the standard of care over conventional 3D conformal radiotherapy, whereas HDR-BT boost is an acceptable treatment option for selected patients with intermediate-risk and high-risk prostate cancer. SBRT and proton therapy should not be used for patients (regardless of disease risk group) outside the setting of a clinical trial. Finally, comparative effectiveness research should be conducted to provide a framework for evaluating advanced radiotherapy technologies by comparing the benefits and harms of available therapeutic options to optimize the risk:benefit ratio and improve cost effectiveness.

Purpose: We report updated results of magnetic resonance imaging guided partial prostate brachytherapy and propose a definition of biochemical failure following focal therapy., Materials and Methods: From 1997 to 2007, 318 men with cT1c, prostate specific antigen less than 15 ng/ml, Gleason 3 + 4 or less prostate cancer received magnetic resonance imaging guided brachytherapy in which only the peripheral zone was targeted. To exclude benign prostate specific antigen increases due to prostatic hyperplasia, we investigated the usefulness of defining prostate specific antigen failure as nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year. Cox regression was used to determine the factors associated with prostate specific antigen failure., Results: Median followup was 5.1 years (maximum 12.1). While 36 patients met the nadir +2 criteria, 16 of 17 biopsy proven local recurrences were among the 26 men who also had a prostate specific antigen velocity greater than 0.75 ng/ml per year (16 of 26 vs 1 of 10, p = 0.008). Using the nadir +2 definition, prostate specific antigen failure-free survival for low risk cases at 5 and 8 years was 95.1% (91.0-97.3) and 80.4% (70.7-87.1), respectively. This rate improved to 95.6% (91.6-97.7) and 90.0% (82.6-94.3) using nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year. For intermediate risk cases survival was 73.0% (55.0-84.8) at 5 years and 66.4% (44.8-81.1) at 8 years (the same values as using nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year)., Conclusions: Requiring a prostate specific antigen velocity greater than 0.75 ng/ml per year in addition to nadir +2 appears to better predict clinical failure after therapies that target less than the whole gland. Further followup will determine whether magnetic resonance imaging guided brachytherapy targeting the peripheral zone produces comparable cancer control to whole gland treatment in men with low risk disease. However, at this time it does not appear adequate for men with even favorable intermediate risk disease., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Combined transperineal prostate brachytherapy and external beam radiation therapy (EBRT) is widely used for treatment of prostate cancer. Long-term efficacy and toxicity results of a multicenter phase 2 trial assessing combination of EBRT and transperineal prostate brachytherapy boost with androgen deprivation therapy (ADT) for intermediate-risk prostate cancer are presented., Methods: Intermediate-risk patients per Memorial Sloan-Kettering Cancer Center/National Comprehensive Cancer Network criteria received 6 months of ADT, and 45 grays (Gy) EBRT to the prostate and seminal vesicles, followed by transperineal prostate brachytherapy with I125 (100 Gy) or Pd103 (90 Gy). Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2 and Radiation Therapy Oncology Group late radiation morbidity scoring systems. Disease-free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant, or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive prostate-specific antigen rises>1.0 ng/mL after 18 months from treatment start), the 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan-Meier method was used to estimate DFS and overall survival., Results: Sixty-one of 63 enrolled patients were eligible. Median follow-up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six-year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. Six deaths occurred; only 1 was attributed to prostate cancer. Six-year overall survival was 96.1%., Conclusions: In a cooperative setting, combination of EBRT and transperineal prostate brachytherapy boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate-risk prostate cancer., (Copyright © 2011 American Cancer Society.)

Background: The authors present long-term results from a phase 2 study that assessed the efficacy of transrectal ultrasound hyperthermia plus radiation with or without androgen suppression for the treatment of locally advanced prostate cancer., Methods: Patients with clinical T2b-T3bN0M0 disease (according to 1992 American Joint Committee on Cancer [AJCC] criteria) received radiation plus 2 transrectal ultrasound hyperthermia treatments. After the first 4 patients, 6 months of androgen suppression were allowed. The study was designed to assess absolute improvement in the 2-year disease-free survival rate compared with the short-term androgen suppression arm in Radiation Therapy Oncology Group (RTOG) study 92-02., Results: Thirty-seven patients received a total of 72 hyperthermia treatments. The mean cumulative equivalent minutes (CEM) T₉₀ 43°C was 8.4 minutes. According to the 1992 AJCC classification, there were 19 patients with T2b tumors, 8 patients with T2c tumors, 5 patients with T3a tumors, and 5 patients with T3b tumors. The median Gleason score was 7 (range, 6-9), and the median prostate-specific antigen (PSA) level was 13.3 ng/mL (range, 2-65 ng/mL). Thirty-three patients received androgen suppression. At a median follow-up of 70 months (range, 18-110 months), the 7-year overall survival rate was 94%, and 61% of patients remained failure free (according to the American Society for Therapeutic Radiology and Oncology definition for failure free survival). The absolute rate of disease-free survival at 2 years, which was the primary study endpoint, improved significantly (84%) compared with a rate of 64% for similar patients on the 4-month androgen suppression arm of RTOG 92-02. When Phoenix criteria (PSA nadir + 2 ng/mL) were used to define biochemical failure, 89% of patients were failure free at 2 years., Conclusions: Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer appeared to be promising. The current results indicated that further study of hyperthermia for the treatment of prostate cancer with optimal radiation and systemic therapy is warranted., (Copyright © 2010 American Cancer Society.)

Background and Purpose: Hsp72 found in the extracellular milieu has been shown to play an important role in immune regulation. The impact of common cancer therapies on extracellular release of Hsp72 however, has been to date undefined., Materials and Methods: Serum from 13 patients undergoing radiation therapy (XRT) for prostate cancer with or without hormonal therapy (ADT) was measured for levels of circulating serum Hsp72 and pro-inflammatory cytokines (IL-6 and TNF-alpha) using the classical sandwich ELISA technique and the relative expression of CD8(+) T lymphocytes and natural killer (NK) cells was measured using flow cytometry. Mouse orthotopic xenograft of human prostate cancer tumors (DU-145 and PC-3) were used to validate and further characterize the response noted in the clinical setting. The biological significance of tumor released Hsp72 was studied in human dendritic cells (DC) in vitro., Results: Circulating serum Hsp72 levels increased an average of 3.5-fold (median per patient 4.8-fold) with XRT but not with ADT (p=0.0002). Increases in IL-6 (3.3-fold), TNF-alpha (1.8-fold), CD8(+) CTL (2.1-fold) and NK cells (3.2-fold) also occurred. Using PC-3 and DU-145 human prostate cancer xenograft models in mice, we confirmed that XRT induces Hsp72 release primarily from implanted tumors. In vitro studies using supernatant recovered from irradiated human prostate cancer cells point to exosomes containing Hsp72 as a possible stimulator of pro-inflammatory cytokine production and costimulatory molecules expression in human DC., Conclusions: The current study confirms for the first time in an actual clinical setting elevation of circulating serum Hsp72 with XRT. The accompanying studies in mice and in vitro identify the released exosomes containing Hsp72 as playing a pivotal role in stimulating pro-inflammatory immune responses. These findings, if validated, may lead to new treatment paradigms for common human malignancies., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Transperineal prostate brachytherapy (TPPB) can be used with external beam radiation therapy (EBRT) to provide a high-dose conformal boost to the prostate. The results of a multicenter Phase II trial assessing safety of combination of EBRT and TPPB boost with androgen suppression (AST) in treatment of intermediate-risk prostate cancer are present here., Materials and Methods: Patients had intermediate-risk prostate cancer. Six months of AST was administered. EBRT to the prostate and seminal vesicles was administered to 45Gy followed by TPPB using either (125)I or (103)Pd to deliver an additional 100Gy or 90Gy. Toxicity was graded using the National Cancer Institute CTC version 2 and the Radiation Therapy Oncology Group late radiation morbidity scoring systems., Results: Sixty-three patients were enrolled. Median follow-up was 38 months. Side effects of AST including sexual dysfunction and vasomotor symptoms were commonly observed. Apart from erectile dysfunction, short-term Grade 2 and 3 toxicity was noted in 21% and 7%, primarily genitourinary related. Long-term Grade 2 and 3 toxicities were noted in 13% and 3%. Two patients had Grade 3 dysuria that resolved with longer follow-up. The most common Grade 2 long-term toxicity was urinary frequency (5%). No biochemical or clinical evidence of progression was noted for the entire cohort., Conclusions: In a cooperative group setting, combination EBRT and TPPB boost with 6 months of AST was generally well tolerated with expected genitourinary and gastrointestinal toxicities. Further follow-up will be required to fully assess long-term toxicity and cancer control.

External-beam radiation therapy (EBRT) combined with brachytherapy is an attractive treatment option for selected patients with clinically localized prostate cancer. This therapeutic strategy offers dosimetric coverage if local-regional microscopic disease is present and provides a highly conformal boost of radiation to the prostate and immediate surrounding tissues. Either low-dose-rate (LDR) permanent brachytherapy or high-dose-rate (HDR) temporary brachytherapy can be combined with EBRT; such combined-modality therapy (CMT) is typically used to treat patients with intermediate-risk to high-risk, clinically localized disease. Controversy persists with regard to indications for CMT, choice of LDR or HDR boost, isotope selection for LDR, and integration of EBRT and brachytherapy. Initial findings from prospective, multicenter trials of CMT support the feasibility of this strategy. Updated results from these trials as well as those of ongoing and new phase III trials should help to define the role of CMT in the management of prostate cancer. In the meantime, long-term expectations for outcomes of CMT are based largely on the experience of single institutions, which demonstrate that CMT with EBRT and either LDR or HDR brachytherapy can provide freedom from disease recurrence with acceptable toxicity.

Purpose: This study was performed to define the rectal dose constraint that would predict late rectal bleeding requiring argon plasma coagulation (APC) following prostate brachy mono-therapy., Methods and Materials: Between February 1999 and April 2002, 91 patients with low risk prostate cancer underwent permanent I(125) radioactive seed implantation without the use of supplemental external beam radiation or androgen suppression therapy. Patients received both CT and MRI scans 6 weeks postimplant for evaluation of dosimetry. The CT and MRI scans were fused. Rectal volumes were contoured on the T2 weighted MR images. For those patients requiring APC, the date on which a patient reported rectal bleeding was recorded. A Cox regression analysis was performed to assess whether there was a significant association between the rectal volume (continuous) exceeding 100 Gy time rectal bleeding. Comparisons of estimates of rectal bleeding requiring APC were made using a 2-sided log rank test., Results: There was a significant association (hazard ratio = 5.6 [95% confidence interval: 1.3, 23.8]; P = 0.002) between the rectal volume exceeding 100 Gy and rectal bleeding requiring APC. After a median follow-up of 4.25 (1-6) years, no patient with less than a median value of 8 cc of rectum exceeding 100 Gy required APC, whereas 20% (P = 0.004) were estimated to require APC within 3 years following treatment., Conclusions: Keeping the rectal volume receiving more than 100 Gy below 8 cc will minimize the risk of rectal bleeding requiring APC following I(125) permanent prostate brachy mono-therapy.

Purpose: To identify an association between perineural invasion (PNI) and cancer-specific survival in patients with prostate cancer after standard-dose external beam radiation therapy (RT)., Methods and Materials: A total of 517 consecutive patients who underwent RT (median dose, 70.5 Gy) between 1989 and 2003 for low-risk or intermediate-risk prostate cancer were studied. A genitourinary pathologist (AAR) scored presence or absence of PNI on all prostate needle-biopsy specimens. A Cox regression multivariable analysis was performed to assess whether the presence of PNI was associated with risk of prostate cancer-specific mortality after RT when the recognized risk-group variables were factored into the model. Estimates of cancer-specific mortality were made using a cumulative incidence method. Comparisons of survival were made using a two-tailed log-rank test., Results: At a median follow-up of 4.5 years, 84 patients (16%) have died, 15 of 84 (18%) from prostate cancer. PNI was the only significant predictor of prostate cancer-specific mortality after RT (p=0.012). The estimated prostate cancer-specific mortality was 14% at 8 years for PNI+ patients vs. 5% for PNI- patients (p=0.0008)., Conclusions: Patients with low- or intermediate-risk prostate cancer who have PNI on prostate needle biopsy have a significantly higher rate of prostate cancer-specific mortality after standard-dose radiation therapy than patients without PNI. Although this analysis is retrospective, this association argues for consideration of the use of more aggressive therapy, such as hormonal therapy with RT or dose escalation, in these select patients.

Objectives: Patients with high-grade clinically localized disease often have disease beyond the prostate and, if so, are unlikely to benefit from radical prostatectomy in the long-term. The objective of this study was to assess whether use of other known prognostic factors could be helpful in defining which men with Gleason 8 to 10 prostate cancer are most likely to benefit from surgical management., Methods: A retrospective analysis was performed on men with biopsy Gleason 8 to 10 prostate cancer who underwent radical prostatectomy at two major university centers. No patients received hormonal therapy as part of initial treatment or adjuvant radiation therapy. Surgery was performed using a retropubic approach, and lymph node dissection was performed in all patients. Risk groups were defined based on prostate-specific antigen (PSA) value and percent positive biopsy cores (%PBC). A Cox proportional hazards analysis was performed to assess for differences in pretreatment prognostic factors. Kaplan-Meier curves were generated for each group, and then comparisons between groups were performed using log-rank analysis to assess for differences in 5-year actuarial freedom from biochemical failure., Results: Radical prostatectomy was performed on 196 patients between 1987 and 2002, of whom 168 had sufficient data for analysis. Median follow-up was 18 months (range, 1 to 130 months), with 31 patients at risk for more than 5 years. Patients with a PSA value of less than 10 ng/mL and %PBC of less than 50% had a 5-year actuarial biochemical control rate of 67% versus 23% for all other patients (P = 0.0001)., Conclusions: PSA value and %PBC are useful in selecting patients with high-grade prostate cancer most likely to benefit by radical prostatectomy.

Purpose: Hyperthermia is used to treat several pelvic tumours. An important step in establishing a broader role for hyperthermia in treatment of prostate cancer is verification of an acceptable toxicity profile. In this report, short- and long-term toxicity profiles of a completed phase II trial of transrectal ultrasound hyperthermia combined with radiation in treatment of locally advanced prostate cancer are presented., Methods and Materials: Thirty-seven patients enrolled on a phase II study of external beam radiation +/- androgen suppression with two transrectal ultrasound hyperthermia treatments were assessed for short- and long-term toxicity. Prostatic and anterior rectal wall temperatures were monitored. Rectal wall temperatures were limited to 40 degrees C (19 patients), 41 degrees C (three patients) and 42 degrees C (15 patients). Univariate logistic regression was used to estimate the log hazard of developing NCI CTC Grade 2 toxicity based on temperature parameters. Hazard ratios, 95% confidence intervals, p-values for statistical significance of each parameter and proportion of variability explained for each of the parameters were calculated., Results: Median follow-up was 42 months. Both short- and long-term GI toxicity were limited to grade 2 or less. Acute grade 2 proctitis was greater for patients with allowable rectal wall temperature of >40 degrees C. Eleven of 18 patients in this group had acute grade 2 proctitis vs three of 19 patients with rectal wall temperatures limited to 40 degrees C (p = 0.004). Long-term grade 2 GI and GU toxicity occurred in 5% and 19% of patients. No late grade 3 or greater toxicity occurred. Late GI and GU toxicity were not associated with the allowable rectal wall temperature., Conclusion: Transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer is safe and well tolerated.

Purpose: To perform a systematic review of the evidence to determine the efficacy and effectiveness of three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer; provide a clear presentation of the key clinical outcome questions related to the use of 3D-CRT in the treatment of localized prostate cancer that may be answered by a formal literature review; and provide concise information on whether 3D-CRT improves the clinical outcomes in the treatment of localized prostate cancer compared with conventional RT., Methods and Materials: We performed a systematic review of the literature through a structured process developed by the American Society for Therapeutic Radiology and Oncology's Outcomes Committee that involved the creation of a multidisciplinary task force, development of clinical outcome questions, a formal literature review and data abstraction, data review, and outside peer review., Results: Seven key clinical questions were identified. The results and task force conclusions of the literature review for each question are reported., Conclusion: The technological goals of reducing morbidity with 3D-CRT have been achieved. Randomized trials and follow-up of completed trials remain necessary to address these clinical outcomes specifically with regard to patient subsets and the use of hormonal therapy.

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

Purpose: The need for dose escalation for patients with low-risk clinically localized prostate cancer remains controversial. In this study, we report our pooled institutional experience of low-risk patients treated with a range of "standard" radiation doses to assess outcome in regard to biochemical failure and to determine whether a dose-response relationship exists within this conventional dose range., Methods and Materials: Patients with low-risk clinically localized prostate cancer (T1 or T2a, Gleason grade 6660 cGy). To ensure that any differences in biochemical failure between patients at the lower and higher ends of the dose range used were not masked by analysis of the entire cohort, patients receiving or=6800 cGy were subsequently analyzed separately. Biochemical failure was defined per the ASTRO consensus definition. The log-rank test was used to assess for differences in follow-up and time to biochemical failure. A Kaplan-Meier plot of time to biochemical failure for the initial 3 subgroups was generated., Results: A total of 264 patients were identified. Sixteen patients whose dose was not recorded in the database were excluded from analysis. The median follow-up was 35 months. No significant differences were found in baseline prostate-specific antigen, Gleason grade, or clinical stage among the groups. The overall actuarial rate of 5-year freedom from biochemical failure was 80.2%. By dose level, the 5-year biochemical failure-free rate was 79.2%, 78.4%, and 84.5% for <6660 cGy, 6660 cGy, and >6660 cGy, respectively. These differences were not significant. Subsequently, 45 patients receiving or=6800 cGy. The difference between these groups was not significant. The 5-year freedom from biochemical failure rate for the patients receiving

Purpose: Although hyperthermia has been used for more than two decades in the treatment of pelvic tumors, little is known about the potential impact of heat on rectal toxicity when combined with other treatment modalities. Because rectal toxicity is a concern with radiation and may be exacerbated by hyperthermia, definition of the association of thermal dose parameters with rectal toxicity is important. In this report, we correlate rectal toxicity with thermal dose parameters for patients treated with hyperthermia and radiation for prostate cancer., Methods and Materials: Thirty patients with T2b-T3b disease (1992 American Joint Committee On Cancer criteria) enrolled in a Phase II study of external beam radiation +/- androgen-suppressive therapy with two transrectal ultrasound hyperthermia treatments were assessed for rectal toxicity. Prostatic and anterior rectal wall temperatures were monitored for all treatments. Rectal wall temperatures were limited to 40 degrees C in 19 patients, 41 degrees C in 3 patients, and 42 degrees C in 8 patients. Logistic regression was used to estimate the log hazard of developing National Cancer Institute Common Toxicity Criteria Grade 2 toxicity based on temperature parameters. The following were calculated: hazard ratios, 95% confidence intervals, p values for statistical significance of each parameter, and proportion of variability explained for each parameter., Results: Gastrointestinal toxicity was limited to Grade 2. The rate of acute Grade 2 proctitis was greater for patients with an allowable rectal wall temperature of >40 degrees C. In this group, 7 of 11 patients experienced acute Grade 2 proctitis, as opposed to 3 of 19 patients in the group with rectal wall temperatures limited to 40 degrees C (p = 0.004). Preliminary assessment of long-term toxicity revealed no differences in toxicity. Hazard ratios for acute Grade 2 proctitis for allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax were 9.33 (p = 0.01), 3.66 (p = 0.03), and 2.29 (p = 0.08), respectively. A model combining these three parameters explained 48.6% of the variability among groups., Conclusion: Rectal toxicity correlates with maximum allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax for patients undergoing transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer. Further definition of this association of thermal dose parameters with rectal toxicity in treatment of pelvic malignancies with hyperthermia should advance the goal of delivering thermal therapy in an effective yet safe manner.

This report describes patient tolerance and toxicity of a transrectal ultrasound hyperthermia system used with external beam radiation therapy in treatment of locally advanced prostate cancer. Nine patients with clinical T2B-T3B (4th edition AJCC criteria) disease received external beam radiation therapy, with two hyperthermia treatments scheduled at least 1 week apart during the first 4 weeks of radiation. Five patients also received hormonal therapy. Interstitial and anterior rectal wall thermometry were performed. Median temperature for each treatment (T50) was 40.8 degrees C and mean CEM T90 = 43 degrees C was 3.4 min. Rectal wall temperature was maintained at < or = 40 degrees C. Treatment duration was limited in three of 17 sessions due to positional discomfort which was alleviated with light IV sedation and use of a 'New Life' mattress (Comfortex, Inc. Winoba, MN, USA). Acute toxicity was limited to NCI common toxicity criteria grade 1 and no excess toxicity was noted with full course radiation therapy +/- hormonal therapy. These findings are consistent with those reported in a previous phase I trial assessing this device. Given the favourable toxicity profile demonstrated to date, modification of treatment parameters for this ongoing phase II study have been instituted that should further the efficacy of transrectal ultrasound hyperthermia for treatment of prostate cancer.

Purpose: Larger prostate gland volumes have been associated with long-term urinary morbidity in prostate interstitial radiation therapy utilizing ultrasound image guidance technique. This study was performed to identify the clinical and technical predictors of acute urinary retention following magnetic-resonance (MR)-guided prostate interstitial brachytherapy., Methods and Materials: Fifty patients underwent MR-guided prostate brachytherapy between December 1997 and March 1999. Patient selection was limited to men with stage T1cNXM0 disease, PSA of less than10 ng/mL, biopsy Gleason score not more than 3 + 4, and endorectal coil MR stage T2 disease. Dosimetry plans were developed in the operating room and (125)Iodine sources were implanted using MR real-time guidance. The peripheral zone (PZ) of the prostate gland was defined as the clinical target volume (CTV) and the minimum prescribed dose to the CTV was 137 Gy. The volumes of the PZ, transition zone (TZ), and total prostate gland volume were also determined by MR. Individual source strength ranged from 0.35 to 0.54 microGym(2)/h (NIST 99, median 0.46 microGym(2)/h) and the total implanted activity ranged from 17.0 to 43.1 mCi (median, 28.1 mCi) using 43-120 seeds (median, 79). The seeds were placed using MR-compatible biopsy needles (14-28, median, 19)., Results: The ability of clinical (MR defined prostate, PZ, and TZ volumes) and technical (number of catheters, number of seeds implanted, and total activity) factors to predict AUR for 50 men undergoing MR-guided prostate interstitial brachytherapy were evaluated using univariable and logistic regression multivariable analyses. Six men (12%) experienced AUR within 24 h after removal of the Foley catheter subsequent to prostate brachytherapy. The total number of seeds (p = 0.05), MR determined prostate volume (p < 0.01), and the MR-determined TZ volume (p < 0.01) were significant predictors of AUR on univariable analysis. Utilizing a multivariable logistic regression analysis, the TZ volume was the only significant predictor of AUR (p < 0.01). The prostate volume is highly correlated to the TZ volume (Spearman correlation coefficient of 0. 91) and was thus significant in the univariable analysis; however, the prostate volume did not add prognostic value in multivariable analysis., Conclusion: Benign prostatic hyperplasia (BPH) resulting in an enlarged TZ volume, is the most important predictor of AUR following MR-guided prostate interstitial radiation therapy. Although AUR was significant (60%) in men with moderate BPH (TZ volume >/= 50 cc), it was also self-limiting.

Purpose: A large number of men are diagnosed with early-stage prostate cancer as a result of prostate-specific antigen (PSA) screening. For many of these men, prostatectomy results in long-term freedom from biochemical and clinical failure. Despite limited follow-up data, ultrasound-guided prostate brachytherapy has gained acceptance as a treatment for early-stage prostate cancer, in part due to its favorable side effect profile and brief recovery period. We report on the use of three-dimensional real-time magnetic resonance (MR) guidance, which has several advantages compared with biplanar ultrasound guidance for prostate brachytherapy, including enhanced geometric and dosimetric feedback during the procedure., Materials and Methods: Median clinical target volume coverage of 96% was achieved using MR guidance. The ability to define more precisely the clinical target volume with MR and the use of real-time assessment of dose distribution resulted in an excellent acute side effect profile. Only 19% of patients required oral alpha1 blockers for postimplant urethritis and 9% required temporary reinsertion of the Foley catheter due to acute urinary obstruction., Conclusions: These results compare favorably to those of ultrasound-guided brachytherapy. Further follow-up is needed to ascertain the impact this technique will have on cancer control and long-term quality of life.

Men treated for prostate cancer often have unexpected outcomes despite predictive models based on stage, grade and prostate-specific antigen (PSA). Previous results have indicated that nuclear morphometry can predict patient outcome in urologic malignancies. Application of this analytical method in prostate cancer treated with radiation therapy is limited. We have evaluated the predictive ability of nuclear morphometry in such patients. Histologic sections from 23 men with clinically localized adenocarcinoma of the prostate treated with radiation therapy were studied. Nuclear morphometric parameters were assessed using a previously described and validated system. Univariate and multivariate logistic regression analyses and a Cox proportional hazards model were used to assess the ability of nuclear morphometric parameters to predict recurrence and disease-free interval. Ten patients had no recurrence with median follow-up of 47. 5 months, while 13 had recurrence. Gleason grade was not predictive of treatment outcome. Pre-treatment PSA data, available for only 11 patients, were predictive of treatment outcome. Several nuclear morphometric parameters predicted recurrence, including upper quartile of suboptimal circle fit and upper quartile of feret-diameter ratio. A prognostic factor score incorporating these 2 parameters was derived, which predicted disease-free interval (p = 0.0014). Int. J. Cancer (Pred. Oncol.) 84:594-597, 1999., (Copyright 1999 Wiley-Liss, Inc.)