Biochemical Failure Rates Research Articles

Prostate brachytherapy in Ghana: our initial experience.

PurposeThis study presents the experience of a brachytherapy team in Ghana with a focus on technology transfer and outcome. The team was initially proctored by experienced physicians from Europe and South Africa.Material and methodsA total of 90 consecutive patients underwent either brachytherapy alone or brachytherapy in combination with external beam radiotherapy for prostate carcinoma between July 2008 and February 2014 at Korle Bu Teaching Hospital, Accra, Ghana. Patients were classified as low-risk, intermediate, and high-risk according to the National Comprehensive Cancer Network (NCCN) criteria. All low-risk and some intermediate risk group patients were treated with seed implantation alone. Some intermediate and all high-risk group patients received brachytherapy combined with external beam radiotherapy.ResultsThe median patient age was 64.0 years (range 46-78 years). The median follow-up was 58 months (range 18-74 months). Twelve patients experienced biochemical failure including one patient who had evidence of metastatic disease and died of prostate cancer. Freedom from biochemical failure rates for low, intermediate, and high-risk cases were 95.4%, 90.9%, and 70.8%, respectively. Clinical parameters predictive of biochemical outcome included: clinical stage, Gleason score, and risk group. Pre-treatment prostate specific antigen (PSA) was not a statistically significant predictor of biochemical failure. Sixty-nine patients (76.6%) experienced grade 1 urinary symptoms in the form of frequency, urgency, and poor stream. These symptoms were mostly self-limiting. Four patients needed catheterization for urinary retention (grade 2). One patient developed a recto urethral fistula (grade 3) following banding for hemorrhoids.ConclusionsOur results compare favorably with those reported by other institutions with more extensive experience. We believe therefore that, interstitial permanent brachytherapy can be safely and effectively performed in a resource challenged environment if adequate training and proctoring is provided.

Cyclin D1 silencing suppresses tumorigenicity, impairs DNA double strand break repair and thus radiosensitizes androgen-independent prostate cancer cells to DNA damage.

Patients with hormone-resistant prostate cancer (PCa) have higher biochemical failure rates following radiation therapy (RT). Cyclin D1 deregulated expression in PCa is associated with a more aggressive disease: however its role in radioresistance has not been determined. Cyclin D1 levels in the androgen-independent PC3 and 22Rv1 PCa cells were stably inhibited by infecting with cyclin D1-shRNA. Tumorigenicity and radiosensitivity were investigated using in vitro and in vivo experimental assays. Cyclin D1 silencing interfered with PCa oncogenic phenotype by inducing growth arrest in the G1 phase of cell cycle and reducing soft agar colony formation, migration, invasion in vitro and tumor formation and neo-angiogenesis in vivo. Depletion of cyclin D1 significantly radiosensitizes PCa cells by increasing the RT-induced DNA damages by affecting the NHEJ and HR pathways responsible of the DNA double-strand break repair. Following treatment of cells with RT the abundance of a biomarker of DNA damage, γ-H2AX, was dramatically increased in sh-cyclin D1 treated cells compared to shRNA control. Concordant with these observations DNA-PKcs-activation and RAD51-accumulation, part of the DNA double-strand break repair machinery, were reduced in shRNA-cyclin D1 treated cells compared to shRNA control. We further demonstrate the physical interaction between CCND1 with activated-ATM, -DNA-PKcs and RAD51 is enhanced by RT. Finally, siRNA-mediated silencing experiments indicated DNA-PKcs and RAD51 are downstream targets of CCND1-mediated PCa cells radioresistance. In summary, these observations suggest that CCND1 is a key mediator of PCa radioresistance and could represent a potential target for radioresistant hormone-resistant PCa.

Predictors and rate of adjuvant radiation therapy following radical prostatectomy: A report from the Prostate Cancer Registry.

Long-term data from three randomized trials have demonstrated that adjuvant radiation therapy (ART) reduces the rate of biochemical failure in high-risk men following radical prostatectomy (RP). One of these trials has shown a survival advantage. We investigated the rate of ART in Victoria and the predictors for this treatment. We analysed data from eligible patients who were notified to the Victorian Prostate Cancer Registry (PCR) by 37 Victorian hospitals between 1 August 2008 and 31 October 2011. We defined ART as radiation therapy (RT) delivered within 6 months of RP. Predictors of ART receipt were modelled using adjusted and unadjusted logistic regression. There were 4626 eligible cases from which 2018 underwent RP with recorded date of surgery. Of these eligible prostatectomy cases, a total of 89 received ART. A subgroup of 833 men had an adverse pathologic feature, of whom 78 received ART. In a multivariate model, pathologic tumour stage pT3a (odds ratio (OR) 2.64; 95% confidence interval (CI) 1.4-5.00; P = 0.003), pT3b (OR 4.58; 95% CI 2.12-9.89; P = 0.000), a positive surgical margin (OR 8.91; 95% CI 4.61-17.2; P = 0.000) and pathologic Gleason grade >7 (OR 7.18; 95% CI 1.54-33.6; P = 0.012) predicted receipt of ART. Adverse pathologic features and high pathologic Gleason score predict for receiving ART in Victorian men after RP, but overall, ART is not commonly prescribed. This finding is consistent with other published series and may reflect clinician scepticism regarding the benefit of ART over salvage RT and concern about toxicity and the risk of over treatment.

Treatment outcomes with permanent brachytherapy in high-risk prostate cancer patients stratified into prognostic categories

To determine whether a previously reported substratification system can be extrapolated to patients with high-risk prostate cancer treated with permanent interstitial brachytherapy. Four hundred six National Comprehensive Cancer Network patients with high-risk prostate cancer treated with permanent prostate brachytherapy with or without supplemental external beam radiotherapy were stratified into good (prostate-specific antigen >20 or Gleason score ≥8 or ≥T3), intermediate (prostate-specific antigen >20 and ≥T3), and poor (Gleason score ≥8 with ≥1 additional high-risk feature) prognostic cohorts. Because of only 1 patient with intermediate high-risk disease, the analysis was performed on patients in the good and poor cohorts. Biochemical failure (BF), prostate cancer-specific mortality (PCSM), distant metastasis, and overall mortality were assessed as function of prognostic group. Multiple parameters were evaluated for impact on outcome. With a median followup time of 7.9 years, 10- and 14-year rates of BF and PCSM for the entire cohort were 7.8% and 3.7%, respectively. The BF rate was significantly greater in the poor prognostic category (16.8% vs. 7.8%, p = 0.041). The poor prognostic category was the strongest predictor of BF in univariate and multivariate analyses. No statistically significant differences in PCSM, distant metastasis, or overall mortality were identified between the good and poor prognostic categories. Patients with high-risk prostate cancer treated with a brachytherapy approach have excellent long-term biochemical control and cancer-specific survival. The poor prognostic high-risk category had a higher rate of BF compared with the good prognostic category without a higher rate of PCSM or distant metastasis.

Ten-year outcomes for prostate cancer patients with Gleason 8 through 10 treated with external beam radiation and high-dose-rate brachytherapy boost in the PSA era

High-dose-rate (HDR) brachytherapy boost represents a method to dose escalate in high-risk prostate cancer; the purpose of this analysis is to report long-term outcomes for a group of high-risk patients with Gleason 8 through 10 prostate cancer treated with HDR brachytherapy boost from a multi-national cohort study. Between 1987 and 2002, 483 patients with Gleason 8–10 prostate cancer were treated on four prospective trials of HDR boost. Conformal external beam radiotherapy (EBRT) was delivered to the pelvis (dose range 36–50.4 Gy) along with HDR boost for a combined biologic equivalent dose (BED) of 215–366 Gy (α/β = 1.2) and cumulative dose of 64–72 Gy. Mean/median follow-up was 6.1/5.1 years. The 10-year rates of biochemical control (BC), distant metastases (DM), clinical failure (CF), cause-specific survival (CSS), and overall survival (OS) were 53.5, 22.1, 25.6, 82.6, and 62.7 %, respectively. Androgen deprivation was given in 69.9 % of patients (predominantly short course) but did not significantly improve BC, DM, CSS, or OS. When stratified by initial PSA (iPSA), 10-year outcomes were improved with lower iPSA (<40) including BC (57.4 vs. 10.3 %, p < 0.001); freedom from distant metastases (81.5 vs. 43.4 %, p < 0.001); CSS (85.0 vs. 59.1 %, p < 0.001); and OS (63.8 vs. 47.9 %, p = 0.02). A combination of HDR brachytherapy boost and EBRT provides a high BED with high rates of disease control and excellent disease specific survival for patients with Gleason 8 through 10 prostate cancer even with iPSA up to 40 ng/ml. Hormonal therapy did not improve outcomes in this cohort of patients when the radiation dose was escalated with an HDR prostate boost.

Posttreatment Testosterone Levels Do Not Affect Rates of Biochemical Failure in Men Who Have Undergone Definitive Radiation for Prostate Cancer: Implications for Testosterone Replacement

patient, and the dose-volume histograms (DVHs) were calculated. A SHIM score decline of 5 points or greater from the consult baseline value was considered a moderate-to-significant sexual function decline, whereas a SHIM score decline of 4 points or less was considered a mild-to-no sexual function decline. We compared the DVH differences between these 2 groups of patients. Results: One year after external beam radiation (either definitive or adjuvant), 22 of the evaluable 51 patients (43.1%) have SHIM score declines of 5 points or greater from the baseline value. Twenty-nine patients (56.9%) have SHIM score declines of 4 points or less from the baseline value. Thirteen patients (25.5%) developed severe erectile dysfunction (ED) with 1 year follow-up SHIM scores of 7 or less. The average DVH of penile bulb dose differences between these 3 groups was insignificant. Conclusion: Our study result does not demonstrate a correlation between penile bulb dose and sexual function decline 1 year post-RT for prostate cancer. Author Disclosure: S. Grimm: None. L.J. Scharf: None. M.L. Sobczak: None.

Abstract 4346: Prognostic gene signature for intermediate risk prostate cancer

Abstract The over treatment of prostate cancer patients is a significant concern, as recent clinical trials suggest that many patients are over treated which can lead to significant patient morbidity. Although the Gleason score is a powerful predictor of lethal or indolent disease, a significant proportion (∼40%) of men present with early stage Gleason score (GS) 7 tumors, for whom prognosis is variable. The goal of this study is to develop and optimize a robust prognostic gene signature that can be utilized on formalin fixed paraffin embedded (FFPE) core biopsy tumor material to better classify patients with intermediate risk, GS 7 tumors into good and poor outcome groups. Three gene signatures were derived from publicly available gene expression profiles of the Swedish Watchful Waiting cohort. The Genomic Grade Index consisted of the top 25 molecular signatures discriminating between high (8, 9 &amp; 10) and low (≤ 6) GS tumors. The Lethal Gene Score consisted of the top 25 molecular signatures discriminating between lethal and indolent disease within GS 7 tumors only. A network-based gene signature consisted of 88 genes which accurately stratified GS 7 patients into high risk and low risk groups, resembling the survival curves of high GS and low GS patients. The prognostic capacity of the combined gene signature was tested in silico on the gene expression profiles of the Mayo cohort. Results demonstrated the gene signature's highly robust capacity for differentiating low risk and high risk patients within GS 7 patients. The NanoString nCounter System will be used to quantify mRNA from prostate FFPE blocks to assess the expression of the 138 prognostic genes. 156 archived prostate tumor blocks will be collected from intermediate risk, GS 7 patients enrolled in the 2005 PR5 prostate trial, which also collected 12 years of clinical follow-up information. Results will be correlated with biochemical (PSA) failure rates and overall survival. In short, our findings provide proof-of-principle that through the use of gene signatures it is possible to separate prostate cancer patients of intermediate risk into good and poor outcome groups. Furthermore, they also identify multiple gene candidates whose expression could likely be formulated into a clinically applicable assay, the implementation of which could serve to stratify prostate cancer patients with tumors of intermediate risk into more accurate high and low risk groups. Citation Format: Brian Li, Robin Hallet, Ying Wu, Greg Pong, John Hassell, Sebastien Hotte, Mark Levine, Himansu Lukka, Anita Bane. Prognostic gene signature for intermediate risk prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4346. doi:10.1158/1538-7445.AM2015-4346

Importance of Local Control in Early-Stage Prostate Cancer: Outcomes of Patients With Positive Post-Radiation Therapy Biopsy Results Treated in RTOG 9408

The purpose of this study was to assess the association between positive post-radiation therapy (RT) biopsy results and subsequent clinical outcomes in males with localized prostate cancer. Radiation Therapy Oncology Group study 94-08 analyzed 1979 males with prostate cancer, stage T1b-T2b and prostate-specific antigen concentrations of ≤ 20 ng/dL, to investigate whether 4 months of total androgen suppression (TAS) added to RT improved survival compared to RT alone. Patients randomized to receive TAS received flutamide with luteinizing hormone releasing hormone (LHRH) agonist. According to protocol, patients without evidence of clinical recurrence or initiation of additional endocrine therapy underwent repeat prostate biopsy 2 years after RT completion. Statistical analysis was performed to evaluate the impact of positive post-RT biopsy results on clinical outcomes. A total of 831 patients underwent post-RT biopsy, 398 were treated with RT alone and 433 with RT plus TAS. Patients with positive post-RT biopsy results had higher rates of biochemical failure (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.3-2.1) and distant metastasis (HR = 2.4; 95% CI = 1.3-4.4) and inferior disease-specific survival (HR = 3.8; 95% CI = 1.9-7.5). Positive biopsy results remained predictive of such outcomes after correction for potential confounders such as Gleason score, tumor stage, and TAS administration. Prior TAS therapy did not prevent elevated risk of adverse outcome in the setting of post-RT positive biopsy results. Patients with Gleason score ≥ 7 with a positive biopsy result additionally had inferior overall survival compared to those with a negative biopsy result (HR = 1.56; 95% CI = 1.04-2.35). Positive post-RT biopsy is associated with increased rates of distant metastases and inferior disease-specific survival in patients treated with definitive RT and was associated with inferior overall survival in patients with high-grade tumors.

A randomized trial of 79.2Gy versus 70.2Gy radiation therapy (RT) for localized prostate cancer.

4 Background: RTOG 0126 is a phase III trial for localized prostate cancer (PC) testing whether dose escalation to 79.2Gy with 3DCRT or IMRT will improve overall survival (OS). Methods: Stage cT1b-T2b with Gleason Score (GS) 2-6 and PSA ≥ 10 and &lt;20 or GS 7 and PSA &lt;15 were eligible and randomized to receive 79.2Gy or 70.2Gy. No androgen withdrawal was used. Treatment was 3DCRT or IMRT to 79.2Gy in 44 fractions or 70.2Gy in 39 fractions. The objective was to detect a 23% reduction in mortality hazard (HR=0.77) for 79.2Gy. ASTRO and Phoenix definition was used for biochemical failure (BF). Time to local progression (LP), distant metastases (DM), PC death, and late GI/GU toxicity was calculated from date of registration. OS was estimated by Kaplan Meier and arms compared with log rank test. BF, LP, DM, time to late GI/GU, and PC death were estimated by cumulative incidence method and arms compared with Gray’s test. Results: 1,532 men were randomized, 763 to 79.2Gy and 769 to 70.2Gy. 1,499 were eligible, 751 and 748 in the 79.2Gy and 70.2Gy arms respectively. Median age was 69, 70% had PSA &lt; 10 ng/ml, 84% with GS 7, 57% had T1 disease, and 66% used 3D-CRT. With a median of 7.0 years follow up, the 5 and 10-yr rates of OS are 88% and 67% with 79.2Gy and 89% and 66% with 70.2Gy (p=0.87; HR (95%CI)=0.98 (0.79,1.21)). The ASTRO (Phoenix) BF rates at 5 and 10 yr are 25% (16%) and 30% (26%) with 79.2Gy and 40% (21%) and 45% (43%) with 70.2Gy (both p&lt;0.0001). The 5 and 10-yr rates of LP are 1% and 4% with 79.2Gy and 2% and 8% with 70.2Gy (p=0.0059; HR (95%CI)=0.46 (0.27,0.81)). The 5 and 10 yr rates of DM are 2% and 5% with 79.2Gy and 3% and 8% with 70.2Gy (p=0.026; HR (95%CI)=0.57 (0.35,0.94)). The high dose arm had lower rate of salvage therapy, 13.5% vs 21%, p=0.0002. The 10 yr rates for time to late grade ≥ 2 GI/GU are 22%/15% with 79.2Gy and 16%/10% with 70.2Gy (p=0.0063/p=0.001). Time to late grade ≥ 3 GI was higher for the 79.2Gy arm (p=0.035) but time to late grade ≥ 3 GU toxicity was not (p=0.14). Conclusions: Despite significant improvement in BF, DM, and LP rates, dose escalation did not improve OS. Patients receiving high dose radiation experience more late toxicity. Clinical trial information: NCT00033631.

Treatment outcomes of radiotherapy versus prostatectomy for localized prostate cancer with Gleason 8 or more on biopsy.

120 Background: There have been no prospective randomized controlled trials comparing current treatment options for patients with high-risk localized prostate cancer. This study seeks to compare the biochemical and metastatic outcomes of patients that received definitive radiotherapy (dRT) or radical prostatectomy (RP) for localized prostate cancer with Gleason score ≥ 8 on initial biopsy. Methods: A total of 106 patients met the inclusion criteria of Gleason score ≥ 8 on initial biopsy and biochemical follow-up ≥ 1 year. Seventy-one patients were initially treated with dRT (96% also receiving androgen deprivation therapy) and 35 patients were initially treated with RP (with or without postoperative RT). Our primary endpoint was biochemical failure (BF). For dRT patients, BF was recorded according to the Phoenix Consensus or if extranodal metastasis was diagnosed. For surgical patients, BF was recorded according to American Urological Association guidelines or if extranodal metastasis occurred. If adjuvant/salvage RT was given postoperatively, BF was recorded if PSA ≥ 0.5 on two consecutive measures after completion of RT. Pretreatment characteristics were compared using Pearson Chi-square method and independent samples Mann-Whitney U test. Actuarial rates of BF and metastasis were calculated using the Kaplan-Meier method. Results: Median follow-up for all patients was 5.3 years. There was no statistical difference in clinical T-stage, initial PSA, or months of follow up between patients treated initially with radiotherapy vs. prostatectomy. Patients initially treated with dRT were significantly older than those treated with RP. The dRT group had a lower rate of BF compared to the RP group, p &lt; 0.001. The Kaplan-Meier estimate of BF at 5 years was 7.6% in the dRT group compared to 34.5% in the RP group. Additionally, the Kaplan-Meier estimate of distant metastasis at 10 years was 22.7% in the dRT group compared to 55.9% of the RP group, p = 0.01. Conclusions: For our sample of patients with Gleason score ≥ 8 on initial biopsy, initial treatment with dRT was associated with lower rates of biochemical failure and extranodal metastasis when compared to initial treatment with prostatectomy.

Neoadjuvant hormone therapy following treatment with robotic-assisted radical prostatectomy achieved favorable in high-risk prostate cancer.

PurposePatients with a high risk of prostate carcinoma typically have higher rates of positive surgical margins and biochemical failure following radical prostatectomy and adjuvant hormone therapy. In this study, we assessed the effects of neoadjuvant hormone therapy (NHT) on prostate carcinoma in high-risk patients following robotic-assisted radical prostatectomy (RARP).MethodsThis retrospective study investigated the medical records of 28 patients who underwent RARP between January 2009 and October 2013. Twenty-two patients underwent NHT prior to RARP. Furthermore, six patients did not undergo NHT prior to RARP. Parameters including age, operating time, blood loss, blood transfusion status, and cancer stage were checked against anatomical correlations. Potential predictors of prolonged operating time and prolonged surgical procedures were assessed using multiple logistic regressions.ResultsNHT was shown to be an independent predictor of prolonged total operating time. Tumor stage alterations did not appear to be associated with NHT followed by RARP. The patients who underwent NHT were not more likely to have positive surgical margins, and an increase in patients requiring blood transfusion was not seen.ConclusionNHT appears to increase operative time during RARP. However, the perioperative morbidity of NHT patients undergoing RARP appears to be equivalent with that of non-NHT patients.

Is three-gland-or-less parathyroidectomy a clinical failure for secondary hyperparathyroidism?

To compare the clinical and biochemical outcomes between adequate and inadequate parathyroidectomies in patients with chronic renal failure. All secondary hyperparathyroidism patients who were previously operated in the Marmara University Hospital Breast and Endocrine Surgery Unit were planned to be included in the study. Patients were divided into two groups according to their extent of surgery: "adequate" and "inadequate" surgery groups. "Adequate surgery" was regarded as either subtotal (3½) or total parathyroidectomy. Removing fewer than 3½ parathyroids was defined as "inadequate surgery." Demographic, preoperative clinical symptoms, and their severity, as well as biochemical (e.g., tCa, PTH) findings, were recorded. Patients were followed monthly. The course of biochemical findings (tCa, PTH, P, ALP) and symptoms (by a scoring system of 1-4) was determined by comparing preoperative findings to those at the patient's last follow-up. Primary outcome of the study was treatment failure (biochemical persistence/recurrence) rates in both study cohorts. Secondary outcomes of the study were the levels of biochemical findings and improvement rates of clinical symptoms after parathyroidectomy, as well as complication rates related to the initial surgery in each surgery cohort. Forty-two patients with secondary hyperparathyroidism who underwent parathyroidectomy were included into the study. Twenty-six were male and 16 were female. Median age was 46. Forty (95%) patients had at least one symptom as the indication for surgery, whereas only 2 (5%) patients were asymptomatic, but biochemical findings were the indication. Twenty-two (52%) patients underwent adequate operation, whereas 20 (48%) patients had inadequate operation. Mean follow-up duration after initial parathyroidectomy was 60 [3-244] months. Significantly more patients (n=15; 75%) in the inadequate surgery group had biochemical persistence/recurrence when compared with those (n=8; 36%) who underwent adequate surgery (OR [odds ratio] 5.25; 95% CI 1.38-19.93; p=0.012). However, symptom improvement rates were similar in both adequate and inadequate surgery groups. Although there is high biochemical treatment failure after inadequate parathyroidectomy in patients with renal hyperparathyroidism, clinical symptom improvement rates are also surprisingly high in this patient group. On the other hand, the adequate surgery group also had an increased biochemical failure rate well above expected in longer follow-ups.

C05: How we decrease the rate of positive surgical margin and biochemical failure during laparoscopic radical prostatectomy

C05: How we decrease the rate of positive surgical margin and biochemical failure during laparoscopic radical prostatectomy

Résultats carcinologiques et fonctionnels de l’abord interfascial de la prostatectomie robotique comparé avec l’abord intrafascial

Due to its technical ease and greater precision Robotic Assisted Laparoscopic radical Prostatectomy (RALP) allows a better preservation of the neurovascular bundles, thereby improving functional outcomes. The intrafascial dissection has been proposed to allow a more complete preservation of these bundles. However, this technique harbors a high rate of positive surgical margins, justifying another trend: the interfascial approach. To date, there are still few publications directly comparing these 2 techniques and our study is the first to offer a 2-year follow-up. Our study focused on a two-hundred patients population divided into two consecutive groups. All the patients were continent preoperatively and had a satisfactory IIEF5 score: (1) Group 1 consisted of 100 patients who underwent RALP with the intrafascial approach. They had a mean age of 60.3 years (45-70). The majority of cancers were of the low or moderate risk group of d'Amico. The mean PSA was 7.43ng/ml. Seventy-five patients had a pT2, 24 a pT3 and one patient had a pT4. (2) Group 2 included 100 patients who underwent RALP with the interfascial technique. Patients had a mean age of 61.6±5.96 years (45-72), and their cancers were mostly of the low or moderate risk groups of d'Amico. The mean PSA was 6.3ng/ml. Seventy-four patients had a pT2, 22 a pT3a, and 4 had a pT3b. All patients were evaluated after one and two years of follow-up. Rates of positive surgical margins were 45% and 19% respectively for groups 1 and 2 (P<0.0001). The rates of biochemical failure (PSA>0.2ng/ml) at 2 years were 10% and 3%, respectively for groups 1 and 2 (P=0.0447). At 2 years, 2 patients in group 1 and one patient in group 2 were using 2 or more urinary pads. Erection with or without oral medication was maintained in 65 (65%) and 31 (31%) patients respectively for groups 1 and 2 at one year. At 2 years 86 and 65 patients were having spontaneous erection, respectively in groups 1 and 2 (P=0.0006). In addition, 65 and 55 patients were also capable of sexual penetration, respectively in groups 1 and 2 (P=0.0045). The intrafascial approach exposed to a very high rate of positive surgical margins while offering only a little benefit in the erectile function preservation at 2 years compared to the interfascial variant. In our series, we did not notice any significant difference between the two techniques concerning the urinary continence. 5.

Comparison of Intraoperatively Built Custom Linked (IBCL) Seeds to Free Seeds for LDR Prostate Brachytherapy

Our prostate brachytherapy technique evolved from implanting free seeds using a gun applicator (GA) to using intraoperatively built custom linked (IBCL) seeds constructed with a push-button delivery system. In this work we compare our dosimetric and early clinical outcomes using free vs. IBCL seeds. From April 2005 to June 2012, 197 patients with clinically localized prostate cancer underwent brachytherapy using ultrasound-guidance with real-time intraoperative dosimetry based on the approach of Stock et al at Mount Sinai School of Medicine in New York. From April 2005 through February 2007, free seeds were placed using a GA. Starting in March 2007, brachytherapy was performed with IBCL constructed in the OR as needed during the implant. Length of each link, number of seeds in each link, and position of seeds and spacers in each link were based on optimizing real-time dosimetry. All patients underwent post-operative CT-based dosimetric analysis. Median follow-up was 3.1 years for all patients, 6.4 years for patients with free seeds, and 2.7 years for IBCL patients. Median age at diagnosis was 64 years and 66% were white. Median PSA at diagnosis was 5.97 ng/ml. NCCN risk grouping: low – 54%, intermediate – 39%, and high – 7%. 117 patients received I125 alone and 79 patients received Pd103 plus external beam radiation therapy (EBRT). One patient received Pd103 alone. Median prostate D90 was 172.1 Gy for I125 and 109.3 Gy for Pd103. Median prostate V100, urethra D30, and rectal V100 were 93.6%, 132.3%, and 0.55 cc. IBCL had significantly higher prostate V100 (p = 0.008) and D90 with I-125 (p = 0.008) than for free seeds while the urethra D30 and rectal V100 were not significantly increased (p = 0.443 and p = 0.651, respectively). 5-yr bDFS was 90.6% for intermediate/high-risk patients and 96% for low risk patients. 5-yr bDFS was significantly higher in the low risk group with IBCL at 100% compared to free seeds at 90.2% (p = 0.031). The 5-yr estimates of toxicity ≥ grade 3, urinary retention requiring catheterization, any hematuria, and any rectal bleeding were 3.4%, 4.7%, 10.2%, and 10.4%, respectively, with no significant difference between IBCL and free seeds. The 5-yr rate of rectal bleeding with radiation (RT) changes on colonoscopy was 1.8%. All hematuria resolved on its own with no RT changes on cystoscopy. Prostate implants using free seeds or IBCL seeds provide low rates of early biochemical failure and toxicity in patients with clinically localized prostate cancer. IBCL was associated with higher prostate doses in patients receiving I125without increasing normal tissue doses significantly. Patients with low risk disease had better bDFS with IBCL seeds compared to patients treated with free seeds, but longer follow-up is needed to confirm these findings.

Early PSA level decline is an independent predictor of biochemical and clinical control for salvage postprostatectomy radiotherapy

BackgroundTo improve the early detection of responders to salvage external beam radiotherapy (RT) after radical prostatectomy (RP). MethodsBetween 2002 and 2007, in a single institution, 136 consecutive patients received salvage RT to a dose of 66Gy without androgen-deprivation therapy after RP for a rising prostate-specific antigen (PSA) level. PSA measurements were systematically performed before RT (PSART), at the fifth week of RT (PSA5), and in the follow-up at least twice a year (every 6mo). The PSA level decline during RT was expressed as PSA ratio (PSA5/PSART). Two different definitions of biochemical failure after salvage RT were considered: PSA level>0.4ng/ml and PSA>PSA nadir post-RT +0.4ng/ml. Statistical analyses included univariate and multivariate Cox regression models. ResultsThe median follow-up was 60 months. The 5-year freedom from biochemical and clinical failure rates were 57% (95% CI: 48%–66%) and 92% (95% CI: 87%–97%), respectively. The mean PSA5 was 0.61ng/ml (range: 0–7) and the mean PSA ratio was 0.67 (0–1.7). A PSA ratio<1 was a significant prognostic factor in multivariate analysis for both definitions of biochemical failure (P = 0.01 for both) and for clinical failure (P = 0.005). ConclusionsFor patients undergoing salvage RT after RP for a rising PSA level, the absence of PSA level decline during RT is predictive of biochemical and clinical failure and may be used to rapidly identify poor responders.

Who benefits from hypofractionated radiation therapy for clinically localized prostate cancer: evidence from meta-analysis.

The aim of this study is to explore the oncological outcomes of hypofractionated radiotherapy for patients with prostate cancer. We systematically searched PubMed, Embase, and the Cochrane Library prior to April 2014 and references of relevant original papers and review articles. Unpublished data from meeting abstracts were supplemented. Studies comparing hypofractionated with conventionally fractionated radiotherapy (CFRT) on oncological outcomes of patients with clinically localized prostate cancer were included. Twelve distinct datasets involving 4,572 participants from 13 papers were eligible for this meta-analysis. The biochemical failure rate (BFR) decreases significantly in the hypofractionated radiotherapy (HFRT) group for approximately 30 % (11-43 %). However, no significantly lower prostate cancer-specific survival and overall survival in HFRT group were observed. In subgroup analyses, HFRT without radiation doses reduction was especially effective in controlling BFR (HR = 0.71, 95 % CI 0.53-0.95; P = 0.02). Compared to CFRT, HFRT only yield a consistent advantage on BFR in high-risk patients (HR = 0.61, 95 % CI 0.46-0.82; P = 0.001). Moreover, androgen deprivation therapy (ADT) had no effect on two radiotherapies in controlling BFR. HFRT improves biochemical failure-free survival in patients with clinically localized prostate cancer. Further well-designed trial is needed to confirm our findings.

Effect of positive surgical margins on biochemical failure, biochemical recurrence-free survival, and overall survival after radical prostatectomy: Median long-term results

The aim of this study was to investigate the median long-term effects of positive surgical margin (PSM) and other prognostic factors on biochemical recurrence-free survival, overall survival, and biochemical failure in patients who underwent radical prostatectomy. Our study included 121 patients with pT2-3N0 disease treated between March 2006 and August 2012. The patients were divided into two groups: those with PSM and those with negative surgical margin (NSM). We analyzed the age, clinical and pathological stages, preoperative and postoperative Gleason scores, duration of the follow-up, adjuvant chemo-/radiotherapy, biochemical failure, biochemical recurrence-free survival, and overall survival in these patients. PSM was found in 25 (20%) patients, whereas 96 patients had NSM. The median follow-up time was 46.6 months (range 12–72 months) for the PSM group and 48.3 months (range 7–149 months) for the NSM group. The biochemical failure rate was 24% in the PSM group and 8.3% in the NSM group (p = 0.029). The biochemical recurrence-free survival was found as 76% in the PSM group and 91.7% in the NSM group. The difference between the groups was not statistically significant (p = 0.06). The overall survival was 100% in both groups. The surgical margins of the radical prostatectomy material is an important pathological indicator for biochemical failure at mid long-term follow-up. We did not find any effect of PSM on overall survival or biochemical recurrence-free survival.

Statin use is associated with decreased prostate cancer recurrence in men treated with brachytherapy

Recent in vitro and in vivo evidence has suggested that statin medications may have anticancer activity. We sought to determine whether statin use was associated with improved clinical outcome in men treated with brachytherapy for prostate cancer. A database of men with prostate cancer treated with permanent Iodine-125 brachytherapy between January 1999 and February 2009 was retrospectively analyzed. Standard guidelines (i.e., American Brachytherapy Society selection criteria) were used for selecting patients for brachytherapy. Biochemical failure was defined using the Phoenix definition. From a total of 247 men with prostate adenocarcinoma treated with brachytherapy, 174 patients (70 %) were identified as using statin medications, either during initial visit or during follow-up. Median PSA follow-up was 51 months after date of implant (range 9.4-140.35). Overall biochemical failure rate was 7.3 % (18 patients). On univariate analysis, statin use was associated with significantly improved freedom from biochemical failure [hazard ratio (HR) 0.28; 95 % CI 0.10-0.72; p < 0.01 by log-rank test]. In multivariate Cox analysis performed with the variables statin use, pretreatment PSA, clinical T stage, Gleason score, and D90 or V100, statin use remained significantly associated with improved freedom from biochemical failure (HR 0.288; 95 % CI 0.086-0.886; p = 0.0299). Statin use was associated with a significant improvement in freedom from biochemical failure in this cohort of men treated with brachytherapy for prostate cancer. Further investigation into the favorable effect of statin use on brachytherapy and radiation therapy in general is warranted, including prospective trials.

Biologically effective dose and definitive radiation treatment for localized prostate cancer

It is not clear if prolongation of definitive external radiation therapy for prostate cancer has an effect on biochemical failure. The aim of this work was to evaluate whether the biologically effective dose (BED), and in particular the duration of radiotherapy, intended as overall treatment time, has an effect on biochemical failure rates and to develop a nomogram useful to predict the 6-year probability of biochemical failure. A total of 670 patients with T1-3 N0 prostate cancer were treated with external beam definitive radiotherapy, to a total dose of 72-79.2 Gy in 40-44 fractions. The computed BED values were treated with restricted cubic splines. Variables were checked for colinearity using Spearman's test. The Kaplan-Meier method was used to calculate freedom from biochemical relapse (FFBR) rates. The Cox regression analysis was used to identify prognostic factors of biochemical relapse in the final most performing model and to create a nomogram. Concordance probability estimate and calibration methods were used to validate the nomogram. Neoadjuvant and concomitant androgen deprivation was administered to 475 patients (70%). The median follow-up was 80 months (range 20-129 months). Overall, the 6-year FFBR rate was 88.3%. BED values were associated with higher biochemical failure risk. Age, iPSA, risk category, and days of radiotherapy treatment were independent variables of biochemical failure. A prolongation of RT (lower BED values) is associated with an increased risk of biochemical failure. The nomogram may be helpful in decision making for the individual patient.