Local Recurrence Of Prostate Cancer Research Articles

167 SERUM GLUCOSE IS ASSOCIATED WITH BIOCHEMICAL RECURRENCE IN MEN WITHOUT DIABETES TREATED FOR LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Epidemiology and Natural History I1 Apr 2012167 SERUM GLUCOSE IS ASSOCIATED WITH BIOCHEMICAL RECURRENCE IN MEN WITHOUT DIABETES TREATED FOR LOCALIZED PROSTATE CANCER Jonathan L. Wright, John L. Gore, Michael P. Porter, Daniel W. Lin, Elaine Hu, and Steven Zeliadt Jonathan L. WrightJonathan L. Wright Seattle, WA More articles by this author , John L. GoreJohn L. Gore Seattle, WA More articles by this author , Michael P. PorterMichael P. Porter Seattle, WA More articles by this author , Daniel W. LinDaniel W. Lin Seattle, WA More articles by this author , Elaine HuElaine Hu Seattle, WA More articles by this author , and Steven ZeliadtSteven Zeliadt Seattle, WA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.218AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The hallmark of adult onset diabetes and metabolic syndrome is insulin resistance and hyperglycemia. There is a growing link between hyperinsulinemia and diabetes mellitus and adverse cancer-specific outcomes, including prostate cancer (PCa). Whether glucose levels in men without diabetes negatively affect PCa outcomes is unknown. We explore the relationship between serum glucose at diagnosis and risk of biochemical recurrence (BCR) for men with localized PCa undergoing curative treatment. METHODS Men treated with radical prostatectomy (RP) or radiation therapy (RT) for localized PCa between 2001 and 2010 were identified from the regional Veterans Affairs Network. Serum glucose levels at diagnosis were obtained from medical records and patients were grouped into glucose level quartiles. Patients with diabetes were excluded. BCR was determined based on PSA progression (nadir PSA + 2 for RT; PSA ≥ 0.2 for RP) or secondary therapy. Multivariate Cox regression was performed to determine whether glucose level was associated with PCa BCR after adjusting for age, clinical stage, Gleason Sum, diagnostic PSA, treatment, BMI, race and year of diagnosis. RESULTS We identified 1,867 men undergoing RP or RT for localized PCa. We excluded 22.5% of men due to pre-existing diabetes, leaving 1,447 for analysis. 14% of men experienced PCa recurrence. With each increasing quartile of glucose level, the risk of recurrence increased: compared with men in the lowest glucose level quartile, the risk of recurrence was greater in the 2nd (HR 1.44, 95% CI 0.96 - 2.17), 3rd (HR 1.55, 95% CI 1.02 - 2.35) and highest (HR 1.61, 95% CI 1.01 - 2.56) quartile even after adjusting for clinicopathologic factors associated with BCR. CONCLUSIONS Glucose levels at the time of PCa diagnosis are an independent predictor of PCa BCR for men without diabetes undergoing treatment for localized disease. Further study of this association is warranted as these findings suggest that glucose control may be a modifiable risk factor for biochemical recurrence of localized prostate cancer. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e69-e70 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jonathan L. Wright Seattle, WA More articles by this author John L. Gore Seattle, WA More articles by this author Michael P. Porter Seattle, WA More articles by this author Daniel W. Lin Seattle, WA More articles by this author Elaine Hu Seattle, WA More articles by this author Steven Zeliadt Seattle, WA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Imaging techniques for local recurrence of prostate cancer: For whom, why and how?

Since there are salvage solutions, it is important to detect local recurrence of prostate cancer as early as possible. The first sign is "biochemical failure" in that the prostate specific antigen (PSA) concentration rises again. The definition of biochemical failure varies depending on the initial treatment: PSA greater than 0.2ng/mL after prostatectomy, nadir+2ng/mL after radiotherapy. There is no standardised definition of biochemical failure after cryotherapy, focused ultrasound, or brachytherapy. Magnetic resonance imaging (MRI) (particularly dynamic MRI) can detect local recurrence with good sensitivity. The role of spectroscopy is still under discussion. For the moment, ultrasound techniques are less effective than MRI.

Does Local Recurrence of Prostate Cancer After Radiation Therapy Occur at the Site of Primary Tumor? Results of a Longitudinal MRI and MRSI Study

PurposeTo determine if local recurrence of prostate cancer after radiation therapy occurs at the same site as the primary tumor before treatment, using longitudinal magnetic resonance (MR) imaging and MR spectroscopic imaging to assess dominant tumor location. Methods and MaterialsThis retrospective study was HIPAA compliant and approved by our Committee on Human Research. We identified all patients in our institutional prostate cancer database (1996 onward) who underwent endorectal MR imaging and MR spectroscopic imaging before radiotherapy for biopsy-proven prostate cancer and again at least 2 years after radiotherapy (n = 124). Two radiologists recorded the presence, location, and size of unequivocal dominant tumor on pre- and postradiotherapy scans. Recurrent tumor was considered to be at the same location as the baseline tumor if at least 50% of the tumor location overlapped. Clinical and biopsy data were collected from all patients. ResultsNine patients had unequivocal dominant tumor on both pre- and postradiotherapy imaging, with mean pre- and postradiotherapy dominant tumor diameters of 1.8 cm (range, 1–2.2) and 1.9 cm (range, 1.4–2.6), respectively. The median follow-up interval was 7.3 years (range, 2.7–10.8). Dominant recurrent tumor was at the same location as dominant baseline tumor in 8 of 9 patients (89%). ConclusionsLocal recurrence of prostate cancer after radiation usually occurs at the same site as the dominant primary tumor at baseline, suggesting supplementary focal therapy aimed at enhancing local tumor control would be a rational addition to management.

3-Dimensional Elastic Registration System of Prostate Biopsy Location by Real-Time 3-Dimensional Transrectal Ultrasound Guidance With Magnetic Resonance/Transrectal Ultrasound Image Fusion

We determined the accuracy of the novel Urostation 3-dimensional transrectal ultrasound system (Koelis, La Tranche, France) for image based mapping biopsies in a prostate phantom. The system is capable of 1) registering the 3-dimensional location of each biopsy track in the 3-dimensional prostate volume data and 2) performing elastic image fusion of transrectal ultrasound with magnetic resonance imaging. We used 3 CIRS-053 prostate phantoms containing 3 hypoechoic lesions to perform ultrasound guided biopsy and 3 CIRS-066 phantoms (Computerized Imaging Reference Systems, Norfolk, Virginia) containing 3 isoechoic but magnetic resonance imaging visible lesions to perform magnetic resonance fusion guided biopsy. Three targeted biopsies were done per lesion. Each biopsy tract was injected with gadolinium based magnetic resonance contrast mixed with india ink. Phantoms were then subjected to 1 mm slice magnetic resonance imaging and serial step sectioning to assess the accuracy of targeted biopsy. A total of 27 ultrasound guided biopsies were targeted into 9 hypoechoic lesions. All 27 biopsies (100%) successfully hit the target lesion. For hypoechoic lesions mean ± SD procedural targeting error was 1.52 ± 0.78 mm and system registration error was 0.83 mm, resulting in an overall error of 2.35 mm. Of the 27 magnetic resonance fusion biopsies 24 (84%) hit the lesion. For isoechoic lesions mean procedural targeting error was 2.09 ± 1.28 mm, resulting in an overall error of 2.92 mm. The novel, computer assisted, 3-dimensional transrectal ultrasound biopsy localization system achieved encouraging accuracy with less than 3 mm error for targeting hypoechoic and isoechoic lesions. The ability to register actual biopsy trajectory and perform elastic magnetic resonance/ultrasound image fusion is a significant advantage for future focal therapy application.

Focal salvage therapy for localized prostate cancer recurrence after external beam radiotherapy

The objective of this study was to evaluate the safety, feasibility, side-effect profile, and proof of concept for focal salvage therapy using high-intensity focused ultrasound (HIFU). A registry-based analysis was conducted between 2004 and 2009 of 430 patients who underwent HIFU. Thirty-nine patients received focal salvage therapy for localized recurrence after external beam radiotherapy. Multiparametric magnetic resonance imaging studies combined with transperineal template prostate mapping biopsies or transrectal biopsies were used to localize disease. Validated questionnaires were used to assess functional outcomes. Biochemical failure was defined by using both Phoenix criteria (prostate-specific antigen [PSA] nadir plus 2 ng/mL) and Stuttgart criteria (PSA nadir plus 1.2 ng/mL). The mean pre-HIFU PSA level was 4.6 ng/mL. The median follow-up was 17 months (interquartile range, 10-29 months). International Index of Erectile Function-5 scores decreased from a median ± standard deviation (SD) of 18 ± 16 to 13 ± 21 at 6 months, demonstrating worsening function. Scores on the University of California Los Angeles-Expanded Prostate Cancer Index Composite Urinary domain indicate that pad-free, leak-free continence status was 64%, and the pad-free rate was 87.2% at last follow-up. One rectourethral fistula occurred and spontaneously resolved with urinary and bowel diversion. The actuarial progression-free survival rate (including PSA nonresponders) was 69% at 1 year and 49% at 2 years according to Phoenix criteria. Excluding PSA nonresponders, these rates were 74% and 58%, respectively (Phoenix criteria). The results from this study indicated that focal salvage therapy is a potential strategy for localized recurrence after radiotherapy that may reduce the harms resulting from whole-gland salvage therapies.

The pattern of prostate cancer local recurrence after radiation and and salvage cryoablation

We assessed the pattern of local recurrence after salvage cryoablation of the prostate, and the impact of local recurrence on intermediate-term outcome. One hundred twenty-two patients who underwent salvage cryoablation were studied after a mean follow-up of 56 months. Serial prostate biopsy was carried out after cryoablation. The histopathology of prostate biopsies before and after cryoablation were compared. The prognostic value of post-cryoablation biopsy was assessed with the Cox regression method. 23.1% of patients had a positive biopsy for prostate cancer following salvage cryoablation. Most cancer recurrences occurred in the apex (51.5%), base (21.2%) and seminal vesicles (18.2%). The presence of cancer at the base of the prostate was found to be a prognostic factor for eventual biochemical failure. Overall 5-year biochemical disease-free survival (bDFS) was 28%, however patients with cancer at the base of the prostate had a 5-year bDFS of 0%. Cancer recurrences occurred in areas where aggressive freezing was avoided as it might result in serious problems (e.g., urethro-rectal fistula and incontinence). Post-cryoablation biopsies and the location of persistent disease are of prognostic value.

Whole‐gland salvage high‐intensity focused ultrasound therapy for localized prostate cancer recurrence after external beam radiation therapy

Whole-gland high-intensity focused ultrasound (HIFU) has been used as salvage therapy for local recurrence following external beam radiation therapy for decades. This article describes the use of the Sonablate 500 HIFU system in the salvage setting. An evaluation was performed of a consecutive group of men with biochemical failure after external beam radiation therapy with histologically proven local recurrence and bone-scan and pelvic magnetic resonance imaging to exclude macroscopic metastases, and who chose to have whole-gland salvage HIFU (Sonablate 500) at 2 centers (3 expert HIFU surgeons at each center). The modified Clavien system was used to categorize adverse events and validated questionnaires for functional outcomes. Progression following HIFU treatment was defined as ASTRO-Phoenix criteria (prostate serum antigen [PSA] >nadir+2 ng/mL) and/or a positive biopsy and/or start of hormone therapy. Eighty-four men underwent whole-gland salvage HIFU (2004-2009). Median age, pretreatment serum PSA, and biopsy Gleason score was 68 years (range, 64-72 years), 4.3 ng/mL (range, 1.9-7.9 ng/mL), and 7 (range, 6-7), respectively. Mean follow-up was 19.8 months (range, 3.0-35.1 months). After salvage HIFU, 62% of the men were pad-free and leak-free. Mean International Index of Erectile Function-5 point score fell from 8.8 to 4.7 (P < .001). International Prostate Symptoms Score and RAND-SF36 scores were not affected. Two men developed rectourethral fistulae after 1 salvage procedure. A further 2 fistulae occurred in the 6 men undergoing a second salvage HIFU. Intervention for bladder outlet obstruction was needed in 20% (17 of 84 patients). If PSA nonresponders were included, 1- and 2-year progression-free survival rates were 59% (50 of 84 patients) and 43% (36 of 84 patients), respectively. If PSA nonresponders were excluded, 1- and 2-year progression-free survival rates were 62% (48 of 77 patients) and 48% (37 of 77 patients), respectively. Salvage whole-gland HIFU is a high-risk procedure. Although its use in early cancer control is promising, strategies to better identify metastatic disease prior to salvage therapy and reduce local toxicity are needed to improve on this.

Salvage high‐dose‐rate brachytherapy for local prostate cancer recurrence after radiotherapy – preliminary results

To assess the preliminary clinical results of salvage high-dose-rate brachytherapy (HDR-BT) applied in cases of suspected local recurrence or of residual tumour after radiotherapy. The subjects were 11 patients who met the above conditions and underwent salvage HDR-BT between December 2006 and January 2009. The T stage at the initial treatment was T1c in three patients, T2 in three patients and T3 in five patients. Ten patients received HDR-BT ± electron beam radiation therapy and one patient received proton beam irradiation. Follow-up after the completion of salvage HDR-BT lasted 18-41 months (mean 29 months). A dose of 11.0 Gy radiation was delivered twice (22.0Gy in total), separated by a 6-h interval, on the day the applicators were inserted. Seven of the 11 cases remained in a biochemical non-evidence of disease state. The prostate-specific antigen (PSA) level continuously rose after salvage HDR-BT in three of the four other cases. Hormone administration was initiated in the four cases of PSA recurrence. No G3 or more severe events occurred, and the incidence of G2 was low during this study period. Of the 11 cases treated with salvage HDR-BT, PSA levels remained low in seven cases and the incidence of complications was also low. This suggests that salvage HDR-BT is effective as an option for treatment of local prostate cancer recurrence after radiotherapy.

7009 POSTER DISCUSSION Sensitivity and Specifity to Detect Local Recurrent Prostate Cancer Using Dynamic Contrast Enhanced (DCE) MRI Without Endorectal Coil and MRI Patterns of Post-prostatectomy Recurrence and of Its Response to Salvage Radiotherapy

7009 POSTER DISCUSSION Sensitivity and Specifity to Detect Local Recurrent Prostate Cancer Using Dynamic Contrast Enhanced (DCE) MRI Without Endorectal Coil and MRI Patterns of Post-prostatectomy Recurrence and of Its Response to Salvage Radiotherapy

IJU this issue

In this issue of the Journal, we have one Review Article, five Original Articles, two Short Communications, two Letters to the Editor, and one Meeting Report. This issue starts with an excellent review article on immunohistochemical biomarkers for bladder cancer prognosis by Matsushita et al. (Sagamihara, Japan). Urothelial carcinoma of the bladder (UCB) is an especially complex and heterogeneous disease with a broad spectrum of histologic findings and potentially lethal behavior. Standard prognostic features, such as pathologic stage and grade, have limited ability to predict the outcome for patients with UCB. Therefore, it is important to understand the molecular events that can explain the clinical heterogeneity of UCB. In their review, Matsushita et al. describe the potential for molecular biomarkers, such as cell cycle makers and apoptosis markers, to improve the accuracy of current prediction models for recurrence and survival in patients with UCB. A lymphocele (LC) is the most frequent complication of radical prostatectomy. Khoder et al. (Munich, Germany) retrospectively studied risk factors and possible prevention strategies for LC in 1163 prostate cancer patients with radical prostatectomy. They concluded that pelvic lymphadenectomy was the only independent significant risk factor for the development of post-radical prostatectomy LC and that LC prophylaxis was difficult. Salvage high-intensity focused ultrasound (HIFU) is one of the treatment options for the local recurrence of prostate cancer without metastases after initial radical external beam radiation therapy. Berge et al. (Oslo, Norway) examined health-related quality of life (QOL) after salvage HIFU for localized radiorecurrent prostate cancer using the University of California, Los Angeles Prostate Cancer Index questionnaire. They found that the treatment of localized radiorecurrent prostate cancer with salvage HIFU was associated with clinically significant reductions in urinary and sexual function domains after a mean follow-up of 17.5 months. Nishida et al. (Osaka, Japan) evaluated the diagnostic value of 3.0-Tesla MRI performed prior to biopsy for the detection of prostate cancer and the factors influencing its accuracy by comparing the images and histopathological findings of stepwise sections of prostatectomy specimens. The results indicate that 3.0-Tesla MRI tends to accurately diagnose prostate cancer with high tumor burden and aggressiveness. Hu et al. (Wuhan, China) investigated the effects of the junction protein p130 Crk-associated substance (p130Cas) and the adhesion molecules E-cadherin and β-catenin on the biological behavior of transitional cell carcinoma of the bladder. They found that p130Cas, E-cadherin and β-catenin may be useful predictors of the degree of malignancy of the bladder cancer. Watanabe et al. (Nagoya, Japan) evaluated the effect of periurethral injection of low serum cultured adipose tissue-derived mesenchymal stromal cells (LASC) on urethral function and compared the effects with collagen injection. Periurethrally injected autologous LASC showed myogenic differentiation and exhibited a therapeutic advantage over collagen. This study suggests that ASC cultured in low serum medium have considerable potential as a novel stem cell source for the treatment of stress urinary incontinence. We also have two Short Communications, one on external validation of prognostic models for renal cell carcinoma recurrence in two patient populations by Utsumi et al. (Chiba, Japan) and one on the efficacy of the selective α1a-adrenoceptor antagonist silodosin in medical expulsive therapy for ureteral stones by Itoh et al. (Nagoya, Japan). None declared.

Reirradiation of prostate cancer with rectum preservation: Eradicative high-dose-rate brachytherapy with natural type hyaluronate injection

IntroductionReirradiation of locally recurrent prostate cancer after radiotherapy is limited because of its toxicity to the rectum that is closely adjacent to the prostate. To solve geometric anatomic constraints, including rectal size and distance from the prostate, we developed a technique that modifies the geometry by noninvasive direct intervention. Methods and MaterialsIn a patient with local recurrence of prostate cancer at 18 months after initial radiotherapy of 61.8GyELQ2,3 (gray equivalent in 2Gy/fraction at α/β=3 calculated with linear quadratic [LQ] model) to the prostate, we prescribed 16Gy (60.8GyELQ2,3 or 78.2GyELQ2,1.6) of reirradiation by high-dose-rate brachytherapy, using a bolus injection of native-type hyaluronate to create and maintain a distance between the prostate and the rectum and decrease rectal size during treatment. ResultsThe procedure was achieved in 10min, without complications. Rectal D2cc of the reirradiation was 5.58Gy (9.58GyELQ2,3). Compared with the initial radiation, the gel injection resulted in an improved therapeutic ratio. The patient was regularly followed up at our clinic; at over 3.5 years after reirradiation, there was no evidence of recurrence or radiation-related toxicities greater than Grade 2, maintaining a nadir prostate-specific antigen level of 0.03ng/mL without hormonal therapy. ConclusionWe consider that this technique is useful for achieving safe and curative reirradiation of prostate cancer.

PET and PET/CT in radiation treatment planning for prostate cancer

Molecular imaging by means of PET provides a method to study the metabolic activity of tumors in vivo. 18F- or 11C-choline and occasionally 18F- or 11C-acetate, are used as tracers for prostate cancer, reflecting the phospholipid metabolism. The hybrid technology PET/computed tomography significantly reduces image fusion mismatch. The role of molecular imaging is increasing in radiation treatment planning for prostate cancer. Local prostate cancer recurrence after primary radiation treatment usually originates at the location of the primary tumor. Focusing the dose escalation on the actual tumor is an option to increase tumor control without increasing toxicity. Image-guided radiotherapy and intensity-modulated radiotherapy are prerequisite technologies for applying the simultaneous boost concept. Clinical results are needed in the near future to support the effectiveness of the concept.

High-Intensity Focused Ultrasound (HIFU): Our Experience in the Treatment of Prostate Cancer Relapsing after Radiotherapy

The aim of the study is to evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) treatment in patients with local prostate cancer recurrence after radiotherapy. From February 2009 to June 2010, 14 patients with prostate cancer recurrence after radiotherapy were selected for HIFU treatment; all patients had a positive TRUS-guided biopsy and the absence of distant metastases was confirmed by computer tomography, PET choline or bone scintigraphy. We classified all patients in 3 groups using D'Amico's classification: 4 patients high risk (PSA >20 ng/ml - 8≤ Gleason Score≤ 10 - clinical stage≥T2c), 8 patients intermediate risk (10 <PSA≤20 ng/ml - Gleason Score=7 - clinical stage=T2b), and 2 patients low risk (PSA≤10 ng/ml - Gleason Score≤6 - clinical stage=T1c-T2a). Progression was defined using Stuttgart definition (PSA>PSAnadir+1.2ng/ml) or after adjuvant therapy introduction. All complications were recorded. Of the 14 patients selected, 12 patients underwent HIFU treatments; 2 patients were excluded because of rectal strictures induced by radiotherapy. At a mean 13 months' follow-up, biochemical success rate was obtained in 1 of the high risk patients and in 5 of the low and intermediate risk patients; 1 man died for a disease not correlated with prostate cancer recurrence. Complications included urinary tract infection, acute urinary retentions, urethral strictures and light stress incontinence. In our experience salvage HIFU is a safe treatment option for local relapse after radiotherapy; its efficacy depends on a careful patient selection.

Salvage lymphadenectomy in postprostatectomy patients with prostate-specific antigen recurrence

Despite very good oncological outcomes provided by radical prostatectomy for organ-confined prostate cancer, up to 40% of patients develop a biochemical recurrence (BCR). BCR can be associated with local or distant recurrence of prostate cancer. However, it can be difficult to identify the exact site of recurrence based on traditional diagnostic imaging tools. The introduction of more advanced imaging studies, such as PET/computed tomography scan, has led to the possibility of identifying small sites of recurrence of prostate cancer. Therefore, once the exact site of recurrence has been identified, theoretically new treatment options might be introduced. Few studies have addressed the possibility to perform a selective pelvic/retroperitoneal lymph node dissection in patients with BCR associated with the evidence of nodal uptake at PET/computed tomography scan. The results of such studies are conflicting, since some patients seem to benefit from the removal of recurrent lymph nodes, showing temporary prostate-specific antigen response to salvage surgery. On the other hand, other series showed no benefit for such patients related to this surgical approach. Moreover, the identification of the good candidates to salvage lymph node dissection is needed. Few studies reported a partial or even a complete prostate-specific antigen response to salvage lymph node dissection in patients with nodal recurrence of prostate cancer. However, due to the small number of patients included, to the lack of control groups as well as to the short-term follow-up, to date the available data do not justify the use of this surgical approach out of clinical trials.

Low-dose-rate Brachytherapy as Salvage Treatment of Local Prostate Cancer Recurrence After Radical Prostatectomy

To present our initial experience with brachytherapy used as a salvage procedure for local recurrence of prostate cancer in the prostatic fossa after radical prostatectomy. The patients included 5 consecutive men who underwent brachytherapy as a salvage procedure after radical prostatectomy from December 2006 to March 2008. We used a technique of implanting the local recurrences similar to the American Brachytherapy Society Guidelines for implanting an intact prostate as definitive therapy. Two modifications were made related to the recurrence location: a rare need to manage urethral doses because the recurrence was typically perirectal, and more aggressive management of the dose to the rectum because of this proximity. All patients tolerated the brachytherapy procedure well and showed a decline in the prostate-specific antigen level, with a median nadir of 0.72 ng/mL at a median follow-up of 13 months. The postprocedural symptoms were minor and included limited new-onset urgency. At the last follow-up visit, all patients had prostate-specific antigen doubling times, which have been associated with long median survival times. Salvage brachytherapy for biopsy-proven local recurrence of prostate cancer is a technically feasible alternative to external beam radiotherapy for local control of recurrences in the prostatic fossa in selected patients after radical prostatectomy.

Brachytherapy as salvage treatment for local nodular recurrence of prostate cancer.

86 Background: Men diagnosed with adenocarcinoma of the prostate treated with radical prostatectomy (RP) have a 10% risk of developing local recurrence within 10 years. While the majority of these recurrences are biochemical failures with no foci of disease, we report on a series of 7 patients who had nodular recurrences in the post-surgical bed and subsequently underwent low-dose rate (LDR) brachytherapy as salvage therapy. Methods: Patients who were initially treated with RP and subsequently with salvage LDR I-125 brachytherapy for a nodular recurrence were included in this series. All patients failed biochemically within 10 years of RP and received no other adjuvant or salvage treatment by choice. Nodular recurrences were biopsy confirmed adenocarcinoma, and patients had no evidence of nodal or distant metastasis on imaging or bone scan. All patients consented to salvage with LDR brachytherapy. Follow up post-salvage was at least every 6 months with a serial PSA. Results: Seven patients underwent salvage LDR brachytherapy with median age of 74 (range 63-77) at time of salvage. The median pre-salvage PSA was 4.56. The biopsy Gleason score of the nodular recurrences was 7 or 8. Median volume of nodular recurrence was 16cc, median number of sources was 30, median D90 for nodule was 155.02 Gy, and median rectum V100 was 0.01. Compared to baseline prior to salvage, patients have reported no additional urinary symptoms or sexual side effects from salvage. Patients have been followed for a median of 28 months post-salvage (range 4-48 months) with a median PSA at last follow up of 1.05. Conclusions: This report presents the first known case series of prostate cancer patients treated with RP who developed local nodular recurrences which were then treated with LDR brachytherapy. For patients who develop a nodular recurrence with no other evidence of distant metastases, LDR brachytherapy offers a novel salvage option. No significant financial relationships to disclose.

Prostate cancer: 1HMRS-DCEMR at 3T versus [(18)F]choline PET/CT in the detection of local prostate cancer recurrence in men with biochemical progression after radical retropubic prostatectomy (RRP)

This study compares proton magnetic resonancespectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined techniques at 3T magnet versus [(18)F]choline PET/computed tomography (CT) in the detection of local prostate cancer recurrence in patients with biochemical progression after radical retropubic prostatectomy (RRP). 84 consecutive patients at high risk of local recurrence underwent combined 1HMRSI-DCEMR and 18-Fcholine- PET/CT. MR scan protocol included turbo spin echo (TSE) T2-weighted sequences in the axial, sagittal and coronal planes; three-dimensional (3D) chemical shift imaging (CSI) sequences with spectral/spatial pulses optimized for quantitative detection of choline and citrate; dynamic contrast enhanced gradient-echo (GRE) T1-weighted sequence. The population was divided into two groups. Group A included 28 patients with a lesion size ranging between 5.00mm and 7.2mm and PSA reduction following radiation therapy. Group B included 56 patients with a lesion size between 7.6mm and 19.4mm. Sensitivity, specificity, positive predictive value (PPV) and accuracy were evaluated and receiver operating characteristic (ROC) curves were performed. In Group A combined 1H-MRSI and DCE-MRI showed a sensitivity of 92%, a specificity of 75% (PPV 96%) while PET-CT examination showed a sensitivity of 62% and a specificity of 50% (PPV 88%) in identifying local recurrence. The accuracy of MRI was 89% while PET-CT showed an accuracy of 60%. Areas under the ROC curve (AUC) values for MR and PET-CT were 0.833 and 0.562, respectively. In Group B combined 1H-MRSI and DCEMR showed a sensitivity of 94% and a specificity of 100% (PPV 100%) with accuracy of 94%. PET-CT had a sensitivity of 92% and a specificity of 33% (PPV 98%) with accuracy of 91%. The AUCs for MR and PET-CT values were 0.971 and 0.837, respectively. The diagnostic accuracy of combined 1HMRSI-DCEMR was higher than PET/CT to identify local prostate cancer recurrence, mostly in patients with low biochemical progression after RRP (0.2-2ng/mL).

MicroRNA-100 Expression is Independently Related to Biochemical Recurrence of Prostate Cancer

Abnormal miRNA expression has emerged as crucial factors in carcinogenesis and is important in the comprehension of prostate cancer behavior. We determined the correlation of miRNA expression profiles with prostate cancer progression. We studied frozen specimens from 49 patients treated for prostate cancer with radical prostatectomy. We intentionally chose 28 men without and 21 with biochemical recurrence, defined as prostate specific antigen greater than 0.2 ng/ml. The expression of 14 miRNAs was determined by quantitative reverse transcriptase-polymerase chain reaction. All radical prostatectomy specimens were studied in toto to determine tumor volume, Gleason score and 2002 TNM pathological stage. Benign prostate tissue from benign prostatic hyperplasia served as a control. Four miRNAs were related to tumor recurrence. Using the Cox regression test the risk of recurrence was 3.0, 3.3, 2.7 and 3.4 for high levels of miR-100, miR-145, miR-191 and miR-let7c, respectively. When considering statistically significant clinical variables on univariate analysis of biochemical-free survival, prostate specific antigen and tumor volume, results revealed that miR-100 and tumor volume were independently related to tumor recurrence. A high level of miR-100 is related to biochemical recurrence of localized prostate cancer in patients treated with radical prostatectomy. The role of miR-100 during carcinogenesis must be resolved in future studies to better understand the molecular pathways in which miR-100 is involved. This may open the possibility of using it as a prognostic marker and inspire the development of a target drug.

Inaccuracies in assignment of clinical stage for localized prostate cancer

Recent data have suggested that clinical T stage is not independently associated with biochemical recurrence of localized prostate cancer after radical prostatectomy. One explanation for this lack of predictive power may be the inaccurate application of staging criteria. Data from men in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database with localized prostate cancer (clinical T1-T2) were analyzed. Correct stage was determined by digital rectal examination (DRE) and transrectal ultrasound (TRUS) findings and was compared with the clinical stage reported directly by the practitioner. DRE/TRUS findings and biopsy results were evaluated to determine factors influencing staging errors. The ability of corrected stage to predict biochemical disease recurrence after prostatectomy was assessed using multivariable analysis. Clinical stage was assigned incorrectly in 1370 of 3875 men (35.4%). Errors more commonly resulted in patient downstaging than upstaging (55.1% vs 44.9%; P < .001). Patients with TRUS lesions were more likely to be staged incorrectly than those with abnormal DRE findings (65.8% vs 38.2%; P < .001). Biopsy laterality was found to strongly influence stage assignment. Even after correction of staging errors, there was no association noted between clinical stage and biochemical disease recurrence after radical prostatectomy. Errors in applying clinical staging criteria for localized prostate cancer are common. TRUS findings are frequently disregarded, and practitioners incorrectly incorporate biopsy results when assigning stage. However, staging errors do not appear to account for the inconsistent reliability of clinical stage in predicting prostate cancer outcomes. These findings further challenge the utility of a DRE-based and/or TRUS-based staging system for risk assessment of localized prostate cancer.

Accuracy of multiparametric magnetic resonance imaging in detecting recurrent prostate cancer after radiotherapy

To assess the role of multiparametric magnetic resonance imaging (mp-MRI) of the prostate in evaluating local recurrence of prostate cancer, using transperineal template-guided 5 mm-spaced biopsies as a reference standard, in men treated with external beam radiotherapy (EBRT) for prostate cancer. The study included 13 patients with evidence of biochemical recurrence after EBRT who had undergone mp-MRI and prostate mapping. Each MRI scan (consisting of T1/T2 weighting, dynamic contrast enhancement and diffusion weighting) was reported by two expert uro-radiologists. Each prostate was divided into four regions of interest (ROI), generating 52 paired datasets for analysis. The mean (range) age of the men was 65.5 (55-70) years, the mean prostate-specific antigen (PSA) level before EBRT was 36.6 (4.5-150) ng/mL, the mean time from EBRT to biochemical recurrence was 5.7 (3-10) years and the mean PSA level at the time of recurrence was 7.1 (0.83-27.9) ng/mL. Eleven men had histological evidence of recurrence, with 23 of 52 ROIs involved with cancer. Overall accuracy, as expressed by the area under a receiver-operator curve, was 0.77 and 0.89 for all cancer, with accuracies of 0.86 and 0.93 for those cancers with ≥3 mm biopsy core length. Inter-observer variability was measured by calculating κ coefficients, which showed fair and moderate agreement between radiologists. Interpretation of mpMRI of the prostate after previous EBRT is challenging. Our results show that the accuracy is good using an accurate reference standard. These results need verification in more patients, but have implications for determining presence or absence of local recurrence and subsequent local salvage therapy.