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ImportanceRadiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain.ObjectiveTo determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT).Design, settings, and participantsThis was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivación Androgénica y Radio Terapía (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021.ExposuresHigh-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs).Main outcomes and measuresThe primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months).ResultsThis cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to

ImportanceProstate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear.ObjectivesTo evaluate the prognostic significance of a nomogram that models an individual's risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools.Design, setting, and participantsThis cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021.ExposuresCurative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy.Main outcomes and measuresPSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index.ResultsOf 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P

ContextManagement of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality.ObjectiveTo quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy.Evidence acquisitionWe performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities.Evidence synthesisA total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p

The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p

Simple Summary: In our paper, we examine various facets of prostate cancer lung metastasis. We explore their clinical manifestations, such as respiratory symptoms and potential complications. Diagnostic modalities, including imaging techniques and biomarker analysis, are scrutinized for accurate identification. Treatment strategies, encompassing surgery, radiation therapy, chemotherapy, and targeted therapies, are discussed for their efficacy. Survival outcomes are assessed to gauge the effectiveness of different interventions. Through comprehensive analysis, we aim to provide insights into managing prostate cancer lung metastasis and enhancing patient care and outcomes. Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy. [ABSTRACT FROM AUTHOR]

Clinical trials have established the benefit of androgen deprivation therapy (ADT) combined with radiotherapy in prostate cancer. ADT sensitizes prostate cancer to radiotherapy-induced death at least in part through inhibition of DNA repair machinery, but for unknown reasons, adjuvant ADT provides further survival benefits. Here, we show that androgen receptor (AR) expression and activity are durably upregulated following radiotherapy in multiple human prostate cancer models in vitro and in vivo. Moreover, the degree of AR upregulation correlates with survival in vitro and time to tumor progression in animal models. We also provide evidence of AR pathway upregulation, measured by a rise in serum levels of AR-regulated hK2 protein, in nearly 20% of patients after radiotherapy. Furthermore, these men were three-fold more likely to experience subsequent biochemical failure. Collectively, these data demonstrate that radiotherapy can upregulate AR signaling after therapy to an extent that negatively affects disease progression and/or survival.

Objectives: The objective was to evaluate the diagnostic performance of surveillance11 C-choline positron emission tomography/computed tomography (PET/CT) for the detection of disease relapse in patients with a history of biochemically recurrent (BCR) prostate cancer (PCa) and prostate-specific antigen (PSA) ≤0.1 ng/ml.Materials and Methods: We included patients who had been treated for BCR PCa and had a surveillance11 C-choline PET/CT at serum PSA ≤0.1 ng/ml. Positive surveillance PET/CT was defined as a study that identified a new tracer-avid lesion or new tracer uptake in a previously treated lesion or both. Findings were confirmed against a composite radiologic-pathologic gold standard. Time to recurrence association analyses were performed for disease relapse risk with the use of Cox proportional hazards regression.Results: In total, 13 (12.1%) of the 107 patients had positive surveillance PET/CT scans, confirmed on pathologic assessment (n = 5) and subsequent imaging (n = 8). Among these 13 patients, ten had distant metastases, two had local recurrence, and one had both. Nine of the ten patients with metastases had oligometastatic disease defined as the presence of ≤3 metastases. Serum PSA became detectable again in only seven patients with positive surveillance PET/CT, after a mean interval from surveillance PET/CT of 292 days (range: 105-543 days). We identified an association of N stage with increased risk of recurrence (hazard ratio = 3.85; P = 0.036) although this was not significant after accounting for multiple testing.Conclusions: Surveillance11 C-choline PET/CT can detect early disease relapse at serum PSA ≤0.1 ng/ml in patients with a history of BCR PCa. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively assess acute differences in patient‐reported outcomes in bowel and urinary domains between intensity‐modulated radiotherapy (IMRT) and proton beam therapy (PBT) for prostate cancer. Methods and Materials: Bowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC‐26 were collected in patients with T1‐T2 prostate cancer receiving IMRT or PBT at a tertiary cancer center (2015‐2018). Mean changes in domain scores were analyzed from pretreatment to the end of and 3 months post‐radiotherapy for each modality. A clinically meaningful change was defined as a score change >50% of the baseline standard deviation. Results: A total of 157 patients receiving IMRT and 105 receiving PBT were included. There were no baseline differences in domain scores between cohorts. At the end of radiotherapy, there was significant and clinically meaningful worsening of BF and UO scores for patients receiving either modality. In the BF domain, the IMRT cohort experienced greater decrement (−13.0 vs −6.7, P <.01), and had a higher proportion of patients with clinically meaningful reduction (58.4% vs 39.5%, P =.01), compared to PBT. At 3 months post‐radiotherapy, the IMRT group had significant and clinically meaningful worsening of BF (−9.3, P <.001), whereas the change in BF score of the PBT cohort was no longer significant or clinically meaningful (−1.2, P =.25). There were no significant or clinically meaningful changes in UO or UI 3 months post‐radiotherapy. Conclusions: PBT had less acute decrement in BF than IMRT following radiotherapy. There was no difference between the two modalities in UO and UI. [ABSTRACT FROM AUTHOR]

Purpose To provide updated American College of Radiology (ACR) appropriateness criteria for transrectal ultrasound-guided transperineal interstitial permanent source brachytherapy. Methods and Materials The ACR appropriateness criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Results Permanent prostate brachytherapy (PPB) is a treatment option for appropriately selected patients with localized prostate cancer with low to very high risk disease. PPB monotherapy remains an appropriate and effective curative treatment for low-risk prostate cancer patients demonstrating excellent long-term cancer control and acceptable morbidity. PPB monotherapy can be considered for select intermediate-risk patients with multiparametric MRI useful in evaluation of such patients. High-risk patients treated with PPB should receive supplemental external beam radiotherapy (EBRT) along with androgen deprivation. Similarly, patients with involved pelvic lymph nodes may also be considered for such combined treatment but reported long-term outcomes are limited. Computed tomography–based postimplant dosimetry completed within 60 days of PPB is essential for quality assurance. PPB may be considered for treatment of local recurrence after EBRT but is associated with an increased risk of toxicity. Conclusions Updated appropriateness criteria for patient evaluation, selection, treatment, and postimplant dosimetry are given. These criteria are intended to be advisory only with the final responsibility for patient care residing with the treating clinicians. [ABSTRACT FROM AUTHOR]

Background Management of recurrent prostate cancer (CaP) after radiotherapy (RT) is dependent on accurate localization of the site of recurrent disease. Objective To describe the anatomic patterns and clinical features associated with CaP recurrence following RT identified on advanced imaging. Design, setting, and participants Retrospective review of 184 patients with a rising prostate-specific antigen (PSA) after RT for CaP. Intervention C-11 choline positron emission tomography/computed tomography (CholPET). Outcome measurements and statistical analysis Recurrence patterns were classified as pelvic soft tissue only (as a surrogate for potentially salvageable disease) versus any extrapelvic disease, and clinical features were compared between patterns. Multivariable logistic regression was used to generate a predictive nomogram for extrapelvic recurrence. Discrimination was assessed with a c -index. Results and limitations Recurrence site was identified in 161 (87%) patients, with 95 (59%) sites histologically confirmed. Factors associated with the detection of recurrence included the difference between PSA nadir and PSA at CholPET (odds ratio: 1.30, p < 0.01) and National Comprehensive Cancer Network high-risk classification (odds ratio: 10.83, p = 0.03). One hundred (54.3%) patients recurred in the pelvic soft tissue only, while 61 (33%) had extrapelvic recurrence. Of 21 patients who underwent CholPET prior to meeting the Phoenix criteria of biochemical failure, 15 (71%) had recurrence identified on CholPET with 11 localized to the pelvis. On multivariable analysis, the difference between PSA nadir and PSA at CholPET, time from RT, and National Comprehensive Cancer Network risk group were predictive of recurrence outside of the pelvis, and a nomogram was generated with a c -index of 0.79. Conclusions CholPET identified the site of recurrence in 87% of patients with a rising PSA after RT; most commonly within the pelvis in potentially salvageable locations. A predictive nomogram was generated, and pending external validation, this may aid in assessing the risk of disease beyond the pelvis. These findings underscore the importance of advanced imaging when considering management strategies for patients with a rising PSA following primary RT. Patient summary We identified anatomic patterns of recurrence in patients with a rising prostate-specific antigen after radiotherapy using C-11 choline positron emission tomography/computed tomography. Most recurrences were localized to the pelvis and we were able to generate a tool to aid in disease localization prior to evaluation with advanced imaging. [ABSTRACT FROM AUTHOR]

Purpose We identify sites and patterns of cancer recurrence in patients with post-prostatectomy biochemical relapse using 11 C-choline positron emission tomography/computerized tomography and endorectal coil multiparametric magnetic resonance imaging. Materials and Methods Between January 2008 and June 2015, 2,466 men underwent choline positron emission tomography for suspected prostate cancer relapse at our institution. Of these men 202 did not receive hormone or radiation therapy, underwent imaging with choline positron emission tomography and multiparametric magnetic resonance imaging, and were found to have disease recurrence. Overall patterns of recurrence were described, and factors associated with local only recurrence were evaluated using univariable and multivariable logistic regression. Results Median prostate specific antigen at positive scan was 2.3 ng/ml (IQR 1.4–5.5) with a median time from prostate specific antigen relapse to lesion visualization of 15 months (IQR 4.8–34.2). Of these 202 men 68 (33%) exhibited local only, 45 (22%) local plus metastatic and 89 (45%) metastatic only relapse. Pelvic node only relapse was observed in 39 (19%) men. Median prostate specific antigen at positive imaging for patients with local only, metastatic only and local plus metastatic relapse was 2.3, 2.7 and 2.2 ng/ml (p=0.46), with a median interval from biochemical recurrence to positive scan of 33.5, 7.0 and 15.0 months, respectively (p <0.001). On multivariable analysis time from biochemical recurrence to positive imaging was independently associated with local only recurrence (OR 1.10 for every 6-month increase, p=0.012). Conclusions Combined choline positron emission tomography and multiparametric magnetic resonance imaging evaluation of biochemical recurrence after prostatectomy reveals an anatomically diverse pattern of recurrence. These findings have implications for optimizing the salvage treatment of patients with prostate cancer with relapse following surgery. [ABSTRACT FROM AUTHOR]

Purpose: Limited duration cytoreductive neoadjuvant hormonal therapy (NHT) is used prior to definitive radiotherapeutic management of prostate cancer to decrease prostate volume. The purpose of this study is to examine the effect of NHT on prostate volume before permanent prostate brachytherapy (PPB), and determine associated predictive factors. Material and methods: Between June 1998 and April 2012, a total of 1,110 patients underwent PPB and 207 patients underwent NHT. Of these, 189 (91.3%) underwent detailed planimetric transrectal ultrasound before and after NHT prior to PPB. Regression analysis was used to assess predictors of absolute and percentage change in prostate volume after NHT. Results: The median duration of NHT was 4.9 months with inter quartile range (IQR), 4.2-6.6 months. Prostatespecific antigen (PSA) reduced by a median of 97% following NHT. The mean prostate volume before NHT was 62.5 ± 22.1 cm3 (IQR: 46-76 cm3), and after NHT, it was 37.0 ± 14.5 cm3 (IQR: 29-47 cm3). The mean prostate volume reduction was 23.4 cm3 (35.9%). Absolute prostate volume reduction was positively correlated with initial volume and inversely correlated with T-stage, Gleason score, and NCCN risk group. In multivariate regression analyses, initial prostate volume (p < 0.001) remained as a significant predictor of absolute and percent prostate volume reduction. Total androgen suppression was associated with greater percent prostate volume reduction than luteinizing hormone releasing hormone agonist (LHRHa) alone (p = 0.001). Conclusions: Prostate volume decreased by approximately one third after 4.9 months of NHT, with total androgen suppression found to be more efficacious in maximizing cytoreduction than LHRHa alone. Initial prostate volume is the greatest predictor for prostate volume reduction. [ABSTRACT FROM AUTHOR]

Purpose: To examine specific prostate and urethra dimensions and prostate shape to facilitate the design of a transurethral ultrasonographic imaging device. Methods and Materials: Computed tomographic (CT) data sets were retrospectively evaluated from 191 patients who underwent permanent prostate brachytherapy at our institution. The prostate, rectum, urethra, and bladder were each segmented with imaging software. Collected data and calculations included prostate volume at specific distances from the urethra and rectum, distances from seeds to urethra (SU), distances from seeds to rectum (SR), prostate length, and curvilinear prostatic urethra length. Results: The CT-based, postimplant mean prostate volume was 49 cm³ (range, 22-106 cm³). Mean prostate length was 4.5 cm (range, 3.1-6.0 cm). The mean curvilinear length of the prostatic urethra was 4.5 cm. The mean (standard deviation) prostatic urethra bend was 29.0° (12.2°). The mean surface distance from the prostate to the urethra was 2.9 cm and from the prostate to the rectum w as 4.6 cm (p < 0.001, paired t test). The mean SU distance was 1.6 cm, and the mean SR distance was 2.3 cm (p < 0.001). In the largest prostate, the mean SU distance was 3.9 cm and the mean SR distance was 6.0 cm. Conclusions: A urethral imaging device for prostate brachytherapy and other minimally invasive prostate therapies should ideally have a 6-cm imaging field of view to image all the prostates in this series in a single image. The mean distance from the SU in permanent prostate brachytherapy is less than 70% of the mean SR distance. [ABSTRACT FROM AUTHOR]

Purpose: Effective permanent prostate brachytherapy (PPB) requires precise placement of radioactive seeds in and around the prostate. The impetus for this research is to examine a new ultrasoundbased imaging modality, vibro-acoustography (VA), which may serve to provide a high rate of PPB seed detection while also effecting enhanced prostate imaging. The authors investigate the ability of VA, implemented on a clinical ultrasound (US) scanner and equipped with a quasi-2D (Q2D) array US transducer, to detect and localize PPB seeds in excised prostate specimens. Methods: Nonradioactive brachytherapy seeds were implanted into four excised cadaver prostates. A clinical US scanner equipped with a Q2D array US transducer was customized to acquire both US and C-scan VA images at various depths. The VA images were then used to detect and localize the implanted seeds in prostate tissue. To validate the VA results, computed tomography (CT) images of the same tissue samples were obtained to serve as the reference by which to evaluate the performance of VA in PPB seed detection. Results: The results indicate that VA is capable of accurately identifying the presence and distribution of PPB seeds with a high imaging contrast. Moreover, a large ratio of the PPB seeds implanted into prostate tissue samples could be detected through acquired VA images. Using CT-based seed identification as the standard, VA was capable of detecting 74%-92% of the implanted seeds. Additionally, the angular independency of VA in detecting PPB seeds was demonstrated through a well-controlled phantom experiment. Conclusions: Q2DVA detected a substantial portion of the seeds by using a 2D array US transducer in excised prostate tissue specimens. While VA has inherent advantages associated with conventional US imaging, it has the additional advantage of permitting detection of PPB seeds independent of their orientation. These results suggest the potential of VA as a method for PPB imaging that ultimately may allow US-based real-time intraoperative dosimetry. [ABSTRACT FROM AUTHOR]

Gene therapy has held promise to correct various disease processes. Prostate cancer rep-resents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS) is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To help establish patterns of care and standards of care of interstitial permanent low-dose-rate (LDR) and temporary high-dose-rate brachytherapy for prostate cancer and to compare the results with a similar 1998 American Brachytherapy Society (ABS) survey. Methods and Materials: A comprehensive questionnaire intended to survey specific details of current clinical brachytherapy practice was provided to the participants of the seventh ABS Prostate Brachytherapy School. Responses were tabulated and descriptive statistics are reported. Results: Sixty-five brachytherapy practitioners responded to the survey. Eighty-nine percent (89%) of respondents performed LDR and 49% perform high-dose-rate brachytherapy. The median number of years of experience for LDR brachytherapists increased from 5 to 10 years over the course of the 12 years since the preceding survey. Compared with the first ABS, a smaller proportion of respondents received formal brachytherapy residency training (43% vs. 56%) or formal “hands-on” brachytherapy training (15% vs. 63%). There has been a marked decline in the utilization of the Mick applicator (Mick Radio-Nuclear Instruments, Inc., Mount Vernon, NY, USA) (60% vs. 28%) and an increase in the use of stranded seeds (40% vs. 11%). Compliance with postimplant dosimetry was higher in the 2010 survey. Conclusion: This survey does suggest an evolution in the practice of LDR brachytherapy since 1998 and aids in identifying aspects that require further progress or investigation. ABS guidelines and other practice recommendations appear to impact the practice of brachytherapy. [Copyright &y& Elsevier]

Abstract: Purpose: To provide updated American Brachytherapy Society (ABS) guidelines for transrectal ultrasound-guided transperineal interstitial permanent prostate brachytherapy (PPB). Methods and Materials: The ABS formed a committee of brachytherapists and researchers experienced in the clinical practice of PPB to formulate updated guidelines for this technique. Sources of input for these guidelines included prior published guidelines, clinical trials, published literature, and experience of the committee. The recommendations of the committee were reviewed and approved by the Board of Directors of the ABS. Results: Patients with high probability of organ-confined disease or limited extraprostatic extension are considered appropriate candidates for PPB monotherapy. Low-risk patients may be treated with PPB alone without the need for supplemental external beam radiotherapy. High-risk patients should receive supplemental external beam radiotherapy if PPB is used. Intermediate-risk patients should be considered on an individual case basis. Intermediate-risk patients with favorable features may appropriately be treated with PPB monotherapy but results from confirmatory clinical trials are pending. Computed tomography–based postimplant dosimetry performed within 60 days of the implant is considered essential for maintenance of a satisfactory quality assurance program. Postimplant computed tomography–magnetic resonance image fusion is viewed as useful, but not mandatory. Conclusions: Updated guidelines for patient selection, workup, treatment, postimplant dosimetry, and followup are provided. These recommendations are intended to be advisory in nature with the ultimate responsibility for the care of the patients resting with the treating physicians. [Copyright &y& Elsevier]

The objective of this research is to prospectively evaluate the feasibility of vibroacoustography (VA) imaging in monitoring prostate cryotherapy in an ex vivo model. Baseline scanning of an excised human prostate is accomplished by a VA system apparatus in a tank of degassed water. Alcohol and dry ice mixture are used to freeze two prostate tissue samples. The frozen prostates are subsequently placed within the water tank at 27°C and rescanned. VA images were acquired at prescribed time intervals to characterize the acoustic properties of the partially frozen tissue. The frozen prostate tissue appears in the images as hypoemitting signal. Once the tissue thaws, previously frozen regions show coarser texture than prior to freezing. The margin of the frozen tissue is delineated with a well-defined rim. The thawed cryolesions show a different contrast compared with normal unfrozen prostate. In conclusion, this pilot study shows that VA produces clear images of a frozen prostate at different temperature stages. The frozen tissue appears as a uniform region with well-defined borders that are readily identified. These characteristic images should allow safer and more efficient application of prostatic cryosurgery. These results provide substantial motivation to further investigate VA as a potential modality to monitor prostate cryotherapy intraoperatively. [ABSTRACT FROM AUTHOR]

Purpose: We describe the treatment outcome in 17 patients who received combined salvage brachytherapy and short-term androgen deprivation therapy for local prostate cancer relapse after prior external beam irradiation. Materials and Methods: Median patient age was 68 years. Local relapse after external beam irradiation was confirmed by biopsy. Median prostate specific antigen at local relapse was 4.7 ng/ml. Five of the 17 patients were enrolled in a protocol combining androgen deprivation therapy with brachytherapy and the remaining men were treated off protocol. All patients received neoadjuvant androgen deprivation therapy for a median of 3 months, followed by ultrasound guided brachytherapy using 125I in 9 and 103Pd seeds in 8. Five patients also received adjuvant leuprolide for a median of 6 months. Biochemical failure was defined using the American Society for Therapeutic Radiology and Oncology definition. Toxicity was graded with a modified Radiation Therapy Oncology Group scale. Results: Median followup was 44 months. The actuarial 4-year biochemical control rate was 75%. Three patients died of intercurrent diseases. No prostate cancer mortality or local failure had occurred at last followup. One patient had bone metastasis. No clinical or treatment factor was associated with biochemical control. Grade 3 and 4 genitourinary toxicity developed in 7 (41%) and 1 patients (6%), respectively. Grade 2 and 3 gastrointestinal toxicity occurred in 5 (29%) and 1 patients (6%), respectively. Conclusions: Our series suggests that salvage brachytherapy and short-term androgen deprivation therapy can achieve biochemical control in select patients with local relapse after prior external beam irradiation. The major side effects are urinary complications, including grade 3 and 4 complications in 41% and 6% of cases, respectively. [Copyright &y& Elsevier]

Abstract: Objectives: To assess the impact of clinical selection criteria on pathologic features among patients treated by radical retropubic prostatectomy and to evaluate the implications of broadening eligibility for permanent prostate brachytherapy monotherapy. Methods: A consecutive series of 423 patients with prostate cancer, who underwent diagnostic biopsy and subsequent radical retropubic prostatectomy, were selected for this study. Four subgroups were defined using the American Brachytherapy Society selection criteria, including prostate size limits (group 1), no prostate size limits (group 2A), a modified set of criteria (group 2B), and clinical Stage T1-T2 (group 3). The rates of extraprostatic extension, seminal vesicle invasion, and lymph node involvement were compared. Results: Adverse pathologic features at radical retropubic prostatectomy were noted in 8 (9.3%) of 86 patients in group 1, 11 (5.6%) of 195 patients in group 2A, 35 (12.0%) of 292 patients in group 2B, and 90 (21.8%) of 413 patients in group 3. The rates of extraprostatic extension, seminal vesicle invasion, and lymph node involvement appeared comparable among groups 1 (5.8%, 3.5%, and 0.0%, respectively), 2A (3.6%, 2.1%, and 0.0%, respectively), and 2B (6.9%, 3.8%, and 1.4%, respectively), but were greater in group 3 (9.7%, 7.8%, and 4.4%, respectively). Conclusions: Judicious broadening of the clinical selection criteria may allow a greater number of patients to be eligible for permanent prostate brachytherapy monotherapy by including patients whose risk of having adverse pathologic features is comparable to that of patients currently deemed suitable for permanent prostate brachytherapy monotherapy. Prospective assessment of oncologic outcomes of such an approach is required. [Copyright &y& Elsevier]

The article discusses two different perspectives in the management of extraprostatic tumor extension and/or surgical margin-positive prostate cancer after radical prostatectomy. It discloses the results of several studies which indicate the benefit of adjuvant radiotherapy (RT) in terms of antigen relapse-free survival. It suggests that further study is needed to address the question on the effectiveness of surveillance with timely implementation of salvage RT limited only to those with relapse.

Purpose: To quantify prostate volume (pvol) changes with transrectal ultrasound (TRUS) immediately after permanent prostate brachytherapy (PPB) and to correlate these changes with postimplant computed tomography (CT) volumetrics. To provide data relevant to evaluating the potential of TRUS-based image fusion for intraoperative dosimetry. Methods and Materials: Between July 2000 and January 2003, 177 patients underwent (125)I PPB monotherapy at our institution, and 165 patients provided research authorization. A total of 136 patients (82%) completed 4 imaging studies: planning TRUS, intraoperative pre- and postimplant TRUS, and CT. Results: Mean planning TRUS pvol was 38.7 +/- 11.7 cc standard deviation (SD), 95% confidence interval (CI) (36.7, 40.7). Mean intraoperative TRUS pvol preimplant was 37.1 +/- 11.7 cc SD, 95% CI (35.1, 39.0), and postimplant was 44.5 +/- 15.1 cc SD, 95% CI (42.0, 47.1). The mean ratio of postimplant:preimplant intraoperative TRUS pvols was 1.2 +/- 0.2 SD, 95% CI (1.18, 1.24), and the difference in mean values was 7.5 cc (p < 0.0001). CT performed within 1 day revealed a mean pvol of 47.9 +/- 15.7 cc SD, 95% CI (45.2, 50.5). The mean volumetric ratio of CT to postimplant TRUS pvol was 1.13 +/- 0.36, 95% CI (1.07-1.19). Conclusions: Whereas mean preimplant step-section TRUS pvol measurements are similar, postimplant TRUS and CT measurements have greater variability that depend on initial pvol. CT-based pvol measurements determined a mean of 10.6 hours after implant were more likely to be identical to those of immediate postimplant TRUS in prostates >33 cc. These data are relevant for establishing accuracy in image-fusion based approaches being investigated for real-time intraoperative PPB dosimetry. [ABSTRACT FROM AUTHOR]

Purpose: Limited duration neoadjuvant cytoreductive hormonal therapy (NHT) is used before the definitive radiotherapeutic management of prostate cancer to decrease target volume size and/or to decrease urinary obstructive symptoms. The purpose of this study is to examine the effect of NHT on prostate volume before permanent prostate brachytherapy (PPB) and on prostatic edema after PPB.Methods and Materials: Between May 1998 and February 2004, 408 patients underwent PPB at our institution and provided research authorization for the use of their records. Of these, 122 (30%) underwent NHT. Of the 122, 78 (64%) underwent transrectal ultrasound before the start of NHT. Patients undergoing PPB who received NHT were compared with a similar non-NHT group (N = 286). Detailed measurements of prostate volume were performed by transrectal ultrasound before and after NHT, if applicable. In addition, intraoperative preimplantation transrectal ultrasound and post-implantation transrectal ultrasound were also performed. Post-implantation computed tomography was per formed within 1 day of PPB.Results: The mean duration of NHT was 4.0 +/- 1.1 months (range, 1-8 months). The mean prostate volume before NHT was 63.3 +/- 22.8 cc (range, 19-138 cc), and after NHT (before PPB), it was 41.6 +/- 16.4 cc (18-98 cc). The median prostate volume decrease after NHT was 22.7 cc or 34.9%. There was no significant difference in the degree of postimplantation prostate edema, as measured by the postimplantation to preimplantation ratio (1.18 +/- 0.05 [range, 0.8-1.9]) for the NHT group and 1.21 +/- 0.03 (range, 0.8-1.9) for the non-NHT group (P = 0.5).Conclusions: Prostate volume decreased by approximately one third after 4 months of NHT. NHT did not affect the degree of post-PPB prostatic edema. [ABSTRACT FROM AUTHOR]

Routine permanent prostate brachytherapy (PPB) includes CT-based postimplant dosimetry (PID). A method of identifying different source types from CT data in the same implant volume is described.A previously described automatic method for seed localization using CT data is used in this study. Two cases were analyzed: a PPB case with 103Pd followed by salvage 125I implantation, both performed at another institution, and a cadaver case where 4 different seed types, including ferromagnetic seeds, and fiducials were implanted.Automatic segregation of different seed types with minimal manual correction is demonstrated using the described localization algorithm. The process is confirmed accurate by comparison of plain film radiographs to CT data and digitally reconstructed radiographs.Unique identification of different source types, including PPB seeds, fiducial markers, and ferromagnetic seeds in permanent implants is possible and permits dosimetric analyses that are spatially coincident. [Copyright &y& Elsevier]

: PurposeTo measure the relative ultrasound backscatter of different seed types as a function of seed orientation and to evaluate the corresponding images of these seeds.: Methods and materialsThree seed types were evaluated: OncoSeed (standard), EchoSeed (corrugated), and RAPID Strand(RS). Ultrasound images for angles of incidence varying from 90° (perpendicular) to 20° at 5MHz and 7.5MHz were produced by raster scanning the seeds in a degassed water bath. Seed images were visually inspected and analyzed using the integrated-optical-density (IOD) method.: ResultsCorrugated seeds appear as contiguous objects over the range of frequencies and orientations examined, whereas standard seeds appear as contiguous objects from 90° to 80° only. The ranges and means of the backscattered IOD ratio of the seeds from 85° to 20° were: (corrugated vs. standard) 1.48 to 3.72 (2.32 ± 0.62) for 5 MHz and 1.26 to 3.77 (2.19 ± 0.84) for 7.5 MHz and (corrugated vs. RS) 1.21 to 9.53 (2.98 ± 2.48) for 5 MHz and 1.008 to 10.86 (2.79 ± 3.08) for 7.5 MHz. Backscattered signal increase ranged from 1.66 dB to 20.7 dB for the corrugated seed as compared to the other seeds.: ConclusionsCorrugated seeds produce greater backscatter signal and a more readily identifiable seed image over a large range of seed orientation as compared with standard brachytherapy seeds. [Copyright &y& Elsevier]

In the year 2000, it is estimated that over 20,000 men underwent transperineal interstitial permanent prostate brachytherapy (TIPPB) for treatment of prostate cancer. Trans-urethral ultrasound (TUUS) is a new interactive, real-time 3D imaging method that may be effective in therapy-guidance during and after TIPPB. TUUS provides higher resolution than trans-rectal ultrasound (TRUS). TUUS can be used to accurately localize radioactive seeds and therefore contribute to more accurate determination of radiation dose distribution throughout the tissue after the completion of the procedure, similar to information currently provided by expensive and offline CT scans. A TUUS catheter can be used to acquire 2D section images or 3D volume images for detailed analyses of the prostate and associated tissue. Initial development of TUUS imaging was carried out on an ultrasound-equivalent prostate phantom with cylindrical dummy radiation sources. This was followed by preliminary studies in animals and then in patients. Both CT and TRUS data were acquired in these studies for comparative purposes. Segmentation of the prostate capsule and radioactive seeds was carried out using several semi-automated 3D algorithms and image processing techniques. Presentation of the data to the clinician is provided by a variety of complementary 2D and 3D display methods. In comparison with the CT data, TUUS data provided both greater spatial resolution and better soft tissue differentiation. In comparison to the TRUS data, TUUS data provided greater resolution and better seed localization. Combining these advantages suggests the possibility of TUUS becoming the exclusive imaging method in prostate cancer brachytherapy. [Copyright &y& Elsevier]

Diagnosis and management of prostate cancer post treatment is a large and complex problem, and care of these patients requires multidisciplinary involvement of imaging, medical, and surgical specialties. Imaging capabilities for evaluation of men with recurrent prostate cancer are rapidly evolving, particularly with PET and MRI. At the same time, treatment options and capabilities are expanding and improving. These recommendations separate patients into three broad categories: (1) patients status post-radical prostatectomy, (2) clinical concern for residual or recurrent disease after nonsurgical local and pelvic treatments, and (3) metastatic prostate. This article is a review of the current literature regarding imaging in these settings and the resulting recommendations for imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Purpose: In 2009, the Radiation Therapy Oncology Group (RTOG) genitourinary members published a consensus atlas for contouring prostate pelvic nodal clinical target volumes (CTVs). Data have emerged further informing nodal recurrence patterns. The objective of this study is to provide an updated prostate pelvic nodal consensus atlas.Methods and Materials: A literature review was performed abstracting data on nodal recurrence patterns. Data were presented to a panel of international experts, including radiation oncologists, radiologists, and urologists. After data review, participants contoured nodal CTVs on 3 cases: postoperative, intact node positive, and intact node negative. Radiation oncologist contours were analyzed qualitatively using count maps, which provided a visual assessment of controversial regions, and quantitatively analyzed using Sorensen-Dice similarity coefficients and Hausdorff distances compared with the 2009 RTOG atlas. Diagnostic radiologists generated a reference table outlining considerations for determining clinical node positivity.Results: Eighteen radiation oncologists' contours (54 CTVs) were included. Two urologists' volumes were examined in a separate analysis. The mean CTV for the postoperative case was 302 cm3, intact node positive case was 409 cm3, and intact node negative case was 342 cm3. Compared with the original RTOG consensus, the mean Sorensen-Dice similarity coefficient for the postoperative case was 0.63 (standard deviation [SD] 0.13), the intact node positive case was 0.68 (SD 0.13), and the intact node negative case was 0.66 (SD 0.18). The mean Hausdorff distance (in cm) for the postoperative case was 0.24 (SD 0.13), the intact node positive case was 0.23 (SD 0.09), and intact node negative case was 0.33 (SD 0.24). Four regions of CTV controversy were identified, and consensus for each of these areas was reached.Conclusions: Discordance with the 2009 RTOG consensus atlas was seen in a group of experienced NRG Oncology and international genitourinary radiation oncologists. To address areas of variability and account for new data, an updated NRG Oncology consensus contour atlas was developed. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potential of the imaging modality vibro-acoustography (VA) for imaging of the prostate. Methods: Excised cadaver prostate specimens were embedded in tissue mimicking gel to simulate the properties of surrounding soft tissues. The samples were imaged at various depths using a laboratory prototyped VA imaging system. The recorded signals were used for offline processing and image reconstruction. In a selected subgroup of tissue samples, conventional ultrasound (B-mode) and x-ray imaging were performed for further analysis, evaluation, and validation of the VA images. Results: The imaging results of prostate tissue samples indicate the capability of VA imaging to detect prostatic nodules and lesions. In the prostate sample with an adenocarcinoma, the lesion appears with a clear contrast with respect to its surrounding tissue. The VA images could also identify the presence of calcifications deep inside the prostate tissue. Further, quantifications of the imaging results demonstrate that VA imaging has higher sensitivity to detect the calcifications compared to conventional ultrasound imaging. VA is also capable of visualizing prostatic tissue structures and in some cases can identify the anatomical zones. More specifically, the observed higher texture level in peripheral zones demonstrates the ability of VA to differentiate between prostatic anatomical zones. Conclusions: Imaging results of ex vivo prostate tissues, reveals the potency of VA as a promising tool to detect abnormalities, delineate tissue structures and anatomical zones, and locate calcifications. The results of this pilot study suggest that in vivo VA imaging of the prostate may be of clinical utility. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate late gastrointestinal (GI) and genitourinary (GU) toxicity of moderately hypofractionated intensity-modulated proton therapy (IMPT) targeting the prostate and pelvic lymph nodes.Methods and Materials: A target accrual of 56 patients with high-risk or unfavorable intermediate risk prostate cancer were enrolled into a prospective study (ClinicalTrials.gov: XXX) of moderately hypofractionated IMPT. IMPT with pencil beam scanning was utilized to deliver 6750 and 4500 cGy RBE in 25 daily fractions simultaneously to the prostate and pelvic lymph nodes, respectively. All received androgen deprivation therapy. Late GI and GU toxicity was prospectively assessed using CTCAE v4.0, at baseline, weekly during radiotherapy, 3-month post-radiotherapy, and then every six months. Actuarial rates of late GI and GU toxicity were estimated using Kaplan-Meier method.Results: Median age was 75.5 years. Fifty-four patients were available for late toxicity evaluation. Median follow-up was 43.9 months (range: 16-66). The actuarial rate of late grade ≥ 2 GI toxicity at both 2 and 3 years was 7.4% (95% CI: 0.2-14.2%). The actuarial rate of late grade 3 GI toxicity at both 2 and 3 years was 1.9% (95% CI: 0-5.4%). One patient experienced grade 3 GI toxicity with proctitis. The actuarial rate of late grade ≥ 2 GU toxicity was 20.5% (95% CI: 8.9-30.6%) at 2 years, and 29.2 % (95% CI: 15.5-40.7%) at 3 years. None had grade 3 GU toxicity. The presence of baseline GU symptoms was associated with a higher likelihood of experiencing late grade 2 GU toxicity.Conclusions: A moderately hypofractionated IMPT targeting the prostate and regional pelvic lymph nodes was generally well tolerated. Patients with pre-existing GU symptoms had a higher rate of late grade 2 GU toxicity. A phase III study is needed to assess any therapeutic gain of IMPT, in comparison with photon-based radiotherapy. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about seed migration and extraprostatic seed placement during prostate brachytherapy.

Purpose: To report a multi-institutional outcomes study on permanent prostate brachytherapy (PPB) to 9 years that includes postimplant dosimetry, to develop a postimplant nomogram predicting biochemical freedom from recurrence. Methods and Materials: Cox regression analysis was used to model the clinical information for 5,931 patients who underwent PPB for clinically localized prostate cancer from six centers. The model was validated against the dataset using bootstrapping. Disease progression was determined using the Phoenix definition. The biological equivalent dose was calculated from the minimum dose to 90% of the prostate volume (D90) and external-beam radiotherapy dose using an α/β of 2. Results: The 9-year biochemical freedom from recurrence probability for the modeling set was 77% (95% confidence interval, 73–81%). In the model, prostate-specific antigen, Gleason sum, isotope, external beam radiation, year of treatment, and D90 were associated with recurrence (each p < 0.05), whereas clinical stage was not. The concordance index of the model was 0.710. Conclusion: A predictive model for a postimplant nomogram for prostate cancer recurrence at 9-years after PPB has been developed and validated from a large multi-institutional database. This study also demonstrates the significance of implant dosimetry for predicting outcome. Unique to predictive models, these nomograms may be used a priori to calculate a D90 that likely achieves a desired outcome with further validation. Thus, a personalized dose prescription can potentially be calculated for each patient. [Copyright &y& Elsevier]

Purpose: To investigate the biochemical control rates and survival for Gleason score 7–10 prostate cancer patients undergoing permanent prostate brachytherapy as a function of the biologic effective dose (BED). Methods and Materials: Six centers provided data on 5,889 permanent prostate brachytherapy patients, of whom 1,078 had Gleason score 7 (n = 845) or Gleason score 8–10 (n = 233) prostate cancer and postimplant dosimetry results available. The median prostate-specific antigen level was 7.5 ng/mL (range, 0.4–300). The median follow-up for censored patients was 46 months (range, 5–130). Short-term hormonal therapy (median duration, 3.9 months) was used in 666 patients (61.8%) and supplemental external beam radiotherapy (EBRT) in 620 (57.5%). The patients were stratified into three BED groups: <200 Gy (n = 645), 200–220 Gy (n = 199), and >220 Gy (n = 234). Biochemical freedom from failure (bFFF) was determined using the Phoenix definition. Results: The 5-year bFFF rate was 80%. The bFFF rate stratified by the three BED groups was 76.4%, 83.5%, and 88.3% (p < 0.001), respectively. Cox regression analysis revealed Gleason score, prostate-specific antigen level, use of hormonal therapy, EBRT, and BED were associated with bFFF (p < 0.001). Freedom from metastasis improved from 92% to 99% with the greatest doses. The overall survival rate at 5 years for the three BED groups for Gleason score 8–10 cancer was 86.6%, 89.4%, and 94.6%, respectively (p = 0.048). Conclusion: These data suggest that permanent prostate brachytherapy combined with EBRT and hormonal therapy yields excellent bFFF and survival results in Gleason score 7–10 patients when the delivered BEDs are >220 Gy. These doses can be achieved by a combination of 45-Gy EBRT with a minimal dose received by 90% of the target volume of 120 Gy of 103Pd or 130 Gy of 125I. [Copyright &y& Elsevier]

Purpose: To determine planning target volume (PTV) margins for prostate radiotherapy based on the internal margin (IM) (intrafractional motion) and the setup margin (SM) (interfractional motion) for four daily localization methods: skin marks (tattoo), pelvic bony anatomy (bone), intraprostatic gold seeds using a 5-mm action threshold, and using no threshold. Methods and Materials: Forty prostate cancer patients were treated with external radiotherapy according to an online localization protocol using four intraprostatic gold seeds and electronic portal images (EPIs). Daily localization and treatment EPIs were obtained. These data allowed inter- and intrafractional analysis of prostate motion. The SM for the four daily localization methods and the IM were determined. Results: A total of 1532 fractions were analyzed. Tattoo localization requires a SM of 6.8 mm left–right (LR), 7.2 mm inferior–superior (IS), and 9.8 mm anterior–posterior (AP). Bone localization requires 3.1, 8.9, and 10.7 mm, respectively. The 5-mm threshold localization requires 4.0, 3.9, and 3.7 mm. No threshold localization requires 3.4, 3.2, and 3.2 mm. The intrafractional prostate motion requires an IM of 2.4 mm LR, 3.4 mm IS and AP. The PTV margin using the 5-mm threshold, including interobserver uncertainty, IM, and SM, is 4.8 mm LR, 5.4 mm IS, and 5.2 mm AP. Conclusions: Localization based on EPI with implanted gold seeds allows a large PTV margin reduction when compared with tattoo localization. Except for the LR direction, bony anatomy localization does not decrease the margins compared with tattoo localization. Intrafractional prostate motion is a limiting factor on margin reduction. [Copyright &y& Elsevier]

Purpose: To investigate the biochemical control rate in patients undergoing permanent prostate brachytherapy as a function of the biologically effective dose (BED) and risk group. Methods and Materials: Six centers provided data on 3,928 permanent brachytherapy patients with postimplant dosimetry results. The mean prostate-specific antigen level was 8.9 ng/mL. 125I was used in 2,293 (58%), 103Pd in 1,635, and supplemental external beam radiotherapy in 882 (22.5%) patients. The patients were stratified into low- (n = 2,188), intermediate- (n = 1,188), and high- (n = 552) risk groups and into three BED groups of < 140 Gy (n = 524), 140–200 Gy (n = 2284), and >200 Gy (n = 1,115). Freedom from biochemical disease progression (biochemical freedom from failure [bFFF]) was determined using the American Society for Therapeutic Radiology Oncology and Phoenix definitions and calculated using the Kaplan-Meier method, with factors compared using the log–rank test. Results: The 10-year prostate-specific antigen bFFF rate for the American Society for Therapeutic Radiology Oncology and Phoenix definitions was 79.2% and 70%, respectively. The corresponding bFFF rates for the low-, intermediate-, and high-risk groups was 84.1% and 78.1%, 76.8% and 63.6%, and 64.4% and 58.2%, respectively (p < 0.0001). The corresponding bFFF rate for the three BED groups was 56.1% and 41.4%, 80% and 77.9%, and 91.1% and 82.9% (p < 0.0001). The corresponding bFFF rate for the low-risk patients by dose group was 69.8% and 49.8%, 86% and 85.2%, and 88.1% and 88.3% for the low-, intermediate, and high-dose group, respectively (p <0.0001). The corresponding bFFF rate for the intermediate-risk patients by dose group was 52.9% and 23.1%, 74.1% and 77.7%, and 94.3% and 88.8% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001). The corresponding bFFF rate for high-risk patients by dose group was 19.2% and 41.7%, 61.8% and 53.2%, and 90% and 69.6% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001). Conclusions: These data suggest that permanent brachytherapy dose prescriptions can be customized to risk status. In low-risk patients, achieving a BED of ≥140 Gy might be adequate for prostate-specific antigen control. However, high-risk disease might require a BED dose of ≥200 Gy. [Copyright &y& Elsevier]

The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure. LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer. [ABSTRACT FROM AUTHOR]

• MRI is commonly used at the time of biochemical recurrence following prostatectomy. • The operational characteristics of MRI after biochemical recurrence are unknown. • Sensitivity, specificity, PPV, and NPV of MRI were 61%, 60%, 86%, and 28% • Sensitivity improves with higher PSA, while specificity improves with lower PSA. To determine the operational characteristics of pelvic magnetic resonance imaging (MRI) prior to salvage radiation therapy (SRT) for biochemically recurrent prostate cancer following radical prostatectomy. We reviewed the medical records of 386 patients who underwent MRI prior to SRT. We assessed associations of pre-SRT MRI findings with biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and salvage androgen deprivation therapy (ADT) use following SRT. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI for detecting local recurrence were also calculated. Pre-SRT MRI was positive for local recurrence in 216 patients (56%), indeterminate in 46 (12%), and negative in 124 (32%). On univariate analysis, BCR following SRT was significantly less likely for patients with positive (HR: 0.58, 95% CI: 0.42–0.8) or indeterminate (HR: 0.6: 0.36–1) MRI findings, compared to patients with negative imaging (p = 0.003). These associations remained significant on multivariate analysis (p < 0.05) and across pre-SRT PSA groups. For the entire cohort, the sensitivity of MRI for local recurrence was 61.0% (53.5–68.1%), specificity 60.0% (44.3–73.0%), PPV 86.1% (78.9–91.5%) and NPV 27.6% (19.0–37.5%). Sensitivity of MRI was better in men with higher pre-SRT PSA (80.0% for PSA > 1.0), and specificity was improved with lower pre-SRT PSA (73.9% for PSA 0.1–0.5). Positive or indeterminate MRI findings prior to SRT were associated with improved biochemical control following SRT, across PSA levels. The sensitivity and specificity of MRI for local recurrence were 61% and 58.7%, respectively. [ABSTRACT FROM AUTHOR]

The management of node-positive prostate cancer is highly variable, with both locoregional and systemic treatment options available. With the increasing use of novel imaging techniques such as PSMA-PET and MRI, combined with the increasing use of surgery for high-risk prostate cancer, clinical and pathological regional nodal disease is being detected at a higher rate and at an earlier stage than previously. This creates a window for a potentially curative management approach. The role of radiotherapy including optimal radiation target volumes and dose, as well as the timing and duration of accompanying systemic therapy remains uncertain. At a workshop in 2017, the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group (FROGG) identified variations in the management of node-positive prostate cancer identified on primary staging or on histopathology at radical prostatectomy. FROGG reviewed the literature and developed a set of evidence-based recommendations on the appropriate investigation and management of clinically and pathologically node-positive prostate cancer. These recommendations encompass imaging techniques, radiation treatment target volumes and doses, as well as the use of androgen deprivation therapy. [ABSTRACT FROM AUTHOR]

Abstract Purpose To report outcomes of patients undergoing low-dose-rate (LDR) brachytherapy and investigate factors associated with biochemical failure and survival. Methods Consecutive patients undergoing LDR with I-125 at our institution between 1998 through 2013 for primary intact prostate cancer were examined. Those with low- and intermediate-risk disease receiving LDR with a minimum of 2 years followup and at least one post-LDR prostate-specific antigen (PSA) were included. Results About 974 patients satisfied inclusion criteria. With median followup of 72 months, biochemical failure occurred in 45 patients. Freedom from biochemical failure as defined by the Phoenix criterion was 96% and 88% at 5 and 10 years, worse for intermediate risk as compared with low risk, with 10-year freedom from biochemical failure of 76% versus 92% (hazard ratio [HR] = 3.7, p < 0.001), respectively. On multivariable analysis, increased prebiopsy PSA, Gleason 4 + 3, and no androgen deprivation therapy were associated with biochemical failure. Gleason 4 + 3 was the factor most strongly associated with biochemical failure (HR = 7.01, p < 0.001). No examined factors were associated with local failure. Gleason 4 + 3 disease increased the likelihood of distant metastasis (HR = 12.4, p = 0.003) and prostate cancer–specific death (HR = 13.2, p < 0.001). No difference in outcomes between patients with Gleason 3 + 3 versus 3 + 4 was observed. Conclusions LDR brachytherapy provided excellent outcomes in this large series of patients treated for localized organ-confined prostate cancer. Local recurrence at 10 years was low at 2.1%. Primary Gleason 4 + 3, higher pretreatment PSA, and no receipt of androgen deprivation therapy were the only factors associated with biochemical failure. Primary Gleason 4 disease was also predictive of distant metastases and decreased prostate cancer–specific survival. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8+ T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa).Methods and Materials: Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8+ T-cell subpopulations, including tumor-reactive (TTR), effector memory, central memory (TCM), effector, and naïve T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk.Results: Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5% and 67.6%, respectively. Between baseline and day 14 after mdSBRT, an increase in the TCM cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95% confidence interval, 1.02-1.47]; P = .033), and an increase in the TTR cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95% confidence interval, 0.65-0.98]; P = .032).Conclusions: An increase in the TTR cell subpopulation was protective against the risk of disease progression, and an increase in the TCM cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8+ T-cell subpopulations and by enhancing their antitumor effect. [ABSTRACT FROM AUTHOR]

Abstract The management of patients with biochemical, local, nodal, or oligometastatic relapsed prostate cancer has become more challenging and controversial. Novel imaging modalities designed to detect recurrence are increasingly used, particularly PSMA-PET scans in Australia, New Zealand and some European countries. Imaging techniques such as MRI and PET scans using other prostate cancer-specific tracers are also being utilised across the world. The optimal timing for commencing salvage treatment, and the role of local and/or systemic therapies remains controversial. Through surveys of the membership, the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group (FROGG) identified wide variation in the management of recurrent prostate cancer. Following a workshop conducted in April 2017, the FROGG management committee reviewed the literature and developed a set of recommendations based on available evidence and expert opinion, for the appropriate investigation and management of recurrent prostate cancer. These recommendations cover the role and timing of post-prostatectomy radiotherapy, the management of regional nodal metastases and oligometastases, as well as the management of local prostate recurrence after definitive radiotherapy. [ABSTRACT FROM AUTHOR]

• Salvage brachytherapy is safe and effective for radiorecurrent prostate cancer. • Thirty international experts completed a Delphi consensus study. • Consensus was achieved in 18 of 30 statements. • No single preferred dose, fractionation, or technique was found. Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2–3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study. [ABSTRACT FROM AUTHOR]

Background Patients with lymph node (LN)-positive prostate cancer (PCa) at radical prostatectomy (RP) face a high risk of cancer recurrence. Nevertheless, recurrence patterns of LN-positive PCa and their prognostic significance remain understudied in the literature. Objective To analyze a large single-institution series with long-term follow-up to elucidate the various clinical recurrence patterns of LN-positive PCa and their association with oncologic outcomes. Design, setting, and participants Years 1987–2012 of a prospectively maintained institutional RP registry were queried for men with LN-positive PCa at RP. Clinical recurrences were categorized as local, nodal, skeletal, or visceral. Outcome measurements and statistical analysis In addition to descriptive statistics and Kaplan-Meier analysis, univariable and multivariable Cox proportional hazards models were constructed to predict recurrence and to quantify the impact of recurrence patterns on cancer-specific mortality (CSM). Results and limitations Data from 1011 men with LN-positive PCa at RP were analyzed with 17.6 yr of median follow-up. The 15-yr clinical recurrence rate was 33% (95% confidence interval [CI], 31–35%) for all patients and 52.2% (95% CI, 47.3–57.1%) for patients with biochemical recurrence. The solitary locations were skeletal ( n = 94, 55%), nodal ( n = 59, 34%), local soft tissue ( n = 29, 17%), and visceral ( n = 8, 5%). Significant multivariable predictors of recurrence were Gleason score 8–10, number of positive nodes, pathologic Gleason score, and more recent year of surgery. The 15-yr CSM after clinical recurrence was 80%, with a mean overall survival of 30 mo after recurrence. On multivariable analysis, recurrences after 5 yr from RP (hazard ratio [HR]: 0.05), multiple recurrences (HR: 1.97), skeletal (HR: 3.13), and visceral metastases (HR: 7.43) were independently associated with CSM (all p < 0.05). Conclusions Recurrences after RP for LN-positive PCa are heterogeneous in terms of time from RP, location, and number of concomitant lesions. Patient summary We found that impact of recurrence patterns on cancer-specific mortality varies significantly and allows these patients to be stratified for purposes of prognostication, follow-up, and therapy. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: High-dose-rate (HDR) brachytherapy plays a potential curative role in the treatment of prostate cancer. An expert panel was convened to review the recent literature and reach a consensus on its appropriate clinical applications. Methods and Materials: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Results: A summary of HDR brachytherapy's clinical applications and recent literature review was completed. Three clinical variants were developed to address common HDR dose, fractionations, and indications for its use in definitive therapy for primary and local recurrent prostate cancer. The panel reached a consensus on the specific treatment approaches with numerical rating and commentary. Conclusions: In combining available medical literature and expert opinion, this manuscript may serve as an aid for other practitioners in the appropriate application of HDR brachytherapy for prostate cancer. [Copyright &y& Elsevier]

Purpose: Extraprostatic extension (EPE) of tumor conveys an adverse prognosis in early-stage prostate cancer. Previous studies reported on the linear and radial distance of EPE (EPEr) as measured from the prostate edge. In this study, the correlation of the EPEr from a large whole mount prostatectomy series was determined with respect to the needle biopsy and prostatectomy specimen findings. Methods and Materials: In a 24-month period, 404 patients underwent radical prostatectomy and the specimens were whole mounted. The preoperative records, biopsy findings, and EPEr from these specimens were evaluated. Results: The range of the EPEr distance was 0.0–5.7 mm. A three-category model was used that included 283 patients (70%) with no EPE, 59 (15%) with “near EPE” (range, 0.01–0.59 mm), and 62 (15%) with “far EPE” (≥0.6 mm). Univariate analysis revealed that patient age and prostate volume did not correlate with EPEr, in contrast to all other factors evaluated. Multivariate analysis identified the preoperative serum prostate-specific antigen, the percentage of cancer in the biopsy cores, and clinical tumor stage as significant. However, the Gleason score was not associated with the EPEr. Greater discrimination was possible in estimating the probability of extension in the “near” category than in the “far” category. Conclusion: EPEr is associated with the preoperative prostate-specific antigen level, percentage of cancer in the biopsy cores, and clinical tumor stage. These data might be useful in planning local therapies for prostate cancer, but additional studies identifying factors associated with EPEr beyond 3–5 mm could have relevance regarding the appropriate radiotherapeutic management strategies. [Copyright &y& Elsevier]

Objectives: Interstitial transperineal cryoablation with 17-gauge cryoprobes is an accepted treatment modality for localized prostate cancer. The effectiveness of cryoablation in the treatment of local prostate cancer recurrence after radical retropubic prostatectomy (RRP) is unknown. Methods: We reviewed the outcome of cryoablative treatment in 15 patients for biopsy-proven locally recurrent prostate cancer after RRP. The follow-up data included prostate-specific antigen (PSA) level, imaging findings, side effects, and an assessment of voiding habits. Results: The mean follow-up time for the entire group was 20 months (range 4 to 32). Of the 15 patients, 6 (40%) had sustained declines in the PSA level (cryoablation success group) and 9 (60%) had disease progression (cryoablation failure group), defined as a PSA increase greater than 0.1 ng/mL from the PSA nadir, or the addition of external beam radiotherapy or androgen deprivation therapy. The pre-RRP PSA level and pre-cryoablation PSA level were similar for both groups. The pre-RRP biopsy Gleason scores (P = 0.03), RRP Gleason scores (P = 0.03), and lesion size on magnetic resonance imaging (P = 0.001) were lower in the success group than in the failure group. All patients who were recurrence free after cryotherapy had a biopsy and Gleason score of 6 or less. Of the 15 patients, 3 (20%) developed worsening of post-RRP incontinence. Conclusions: Our preliminary results suggest that salvage cryoablation can be an effective and safe treatment modality and a possible alternative to external beam radiotherapy for targeted control of confirmed local recurrences after RRP, especially in those with favorable biopsy or pathologic Gleason scores before cryotherapy. Larger cohorts and longer follow-up are needed to assess the viability of this treatment. [Copyright &y& Elsevier]

Abstract: Purpose: This study is aimed at understanding and defining the current patterns of care with respect to prostate brachytherapy for patients with intermediate-risk localized disease in the combined academic and community setting. Methods and materials: A nomogram-based survey was developed at the Seattle Prostate Institute defining the accepted criteria for intermediate-risk prostate cancer. Patients were defined as having intermediate-risk prostate cancer if they met one of the following criteria: prostate-specific antigen (PSA) >10ng/dL, Gleason score (GS) ≥7, or cT2b or cT2c disease. Additional potential predictive factors including perineural invasion (PNI), GS 3+4 vs. 4+3, and high-volume disease were included. Results: In the absence of PNI, all of those surveyed would perform monotherapy for intermediate-risk patients, GS 7 (3+4) or PSA 10–20, with cT1c and <30% cores +. Up to 80% would perform monotherapy for patients with cT1c, GS 7 (4+3), and <30% cores +. Eighty to 90% of physicians would perform an implant alone with cT2a and either a PSA of 10–20 or GS of 7 (3+4) and <30% cores +. Fifty to 60% of those surveyed stated that they would treat a patient with cT2b disease, GS 7 (3+4), or PSA 11–20, with less than two-thirds of the biopsy cores positive in the absence of PNI. Conclusions: This Patterns of Care (POC) study reveals that certain subsets of intermediate-risk localized prostate cancer patients are considered appropriate candidates for an interstitial implant alone. [Copyright &y& Elsevier]