Predictor Of Biochemical Failure Research Articles

Undetected Cribriform and Intraductal Prostate Cancer at biopsy is associated with adverse outcomes.

Intraductal carcinoma (IDC) and cribriform pattern (Crib) of prostate cancer are increasingly recognized as independent prognosticators of poor outcome, both in prostate biopsies and radical prostatectomy (RP) specimens. The aim of our project is to assess the impact of false negative biopsies for these two characteristics on oncological outcomes. Patients who underwent RP between January 2015 and December 2022 were included in the study. Predictors of Biochemical Failure were examined using a multivariate Cox proportional hazards model. Among the 836 patients who underwent RP, 233 (27.9%) had Crib, and 125 (15.0%) had IDC on prostate biopsy, with 71 (8.5%) patients having both IDC and Crib. Concerning IDC/Crib status at biopsy, 217 (26%) patients had a false-negative biopsy, 332 (39.7%) had a true-negative biopsy, 256 (30.6%) showed a true-positive biopsy, and 24 (3.7%) exhibited a false-positive biopsy, with respect to either pattern. When comparing false-negative, false-positive, true-negative and true-positive biopsies for IDC/Crib, we found that patients with a false-negative biopsy for IDC/Crib versus those with a true-negative biopsy for IDC/Crib disclosed a rate of advanced pathological stage (≥pT3) which was twice that of patients with a true-negative biopsy for IDC/Crib: 56.8% versus 28.1%, respectively (p < 0.001). On multivariate Cox analysis, log PSA before RP (hazard ratio [HR] 2.07, 95% CI 1.53-2.82; p < 0.001), a higher percentage of positive cores at biopsy ( ≥ 33%) (HR 1.68, 95% CI 1.07-2.63; p = 0.024), and false negative biopsy for IDC/Crib (HR 2.14, 95% CI 1.41-3.25; p < 0.001), were each significantly associated with an increased risk of BCR. A false-negative biopsy for IDC/Crib is independently associated with higher risk of BCR and advanced pathological stage compared to a true negative biopsy.

PO-1788 Radiomic and dosiomic prediction of biochemical failure after Iodine-125 prostate brachytherapy

PO-1788 Radiomic and dosiomic prediction of biochemical failure after Iodine-125 prostate brachytherapy

Prostate-specific antigen density as a predictor of biochemical failure following radical prostatectomy.

Abstract. In Russia, prostate cancer is one of the most common cancers in men. Radical prostatectomy is an established option to treat localized prostate cancer. Almost 35% of patients will face prostate cancer progression within 10 years following radical prostatectomy. Purpose. To assess the ability of PSA density to predict biochemical relapse and detect unfavorable pathological features among patients suffering from localized prostate cancer treated with radical prostatectomy. Material and methods. The study evaluated 147 patients with localized prostate cancer who underwent an open or laparoscopic retropubic radical prostatectomy between February 2001 and August 2015. The assessment of prognostic and clinical significance of PSA density took place. Results. Biochemical recurrence was observed in 53 (36.01%) patients. PSA density (p = 0.006), Gleason score (p = 0.0006), pathological stage T (p = 0.002), extraprostatic extension (p = 0.019), seminal vesicle invasion (p = 0.001) and prostate cancer upstaging (p=0.0007) were found to significantly correlate with biochemical relapse risk. We established a relationship between PSA density and unfavorable pathological features detection following radical prostatectomy. Using ROC – curve analysis (AUC=0,635, р=0,005) we determined PSA density threshold of (&gt;0,309 ng/mL/cc) – when exceeded, was associated with statistically significant decrease in disease – free survival. According to the results of multivariate analysis – PSA density, abnormal Gleason score and seminal vesicle invasion has proven to influence disease – free survival (p &lt; 0.05). Conclusion. We have clearly demonstrated a PSA density as an important prognostic tool of high clinical relevance, which may aid in biochemical relapse risk estimation. A PSA density parameter incorporation into preoperative nomograms may increase the predictive potential of latter.

The surgical learning curve for salvage robot-assisted radical prostatectomy: a prospective single-surgeon study.

The aim of this study was to report the overall results and the learning curve (LC) in salvage robot-assisted radical prostatectomy (sRARP) patients, in terms of morbidity, oncological and functional outcomes in a single surgeon tertiary-referral center. One hundred and twenty patients underwent sRARP by a single surgeon (V.P.) from 2008 to 2018. To assess the trends in the learning experience they were sub-divided in 4 groups of 30 consecutive patients based on date of surgery. The Kaplan-Meier method and regression models were used to identify survival estimations and predictors of potency, continence and biochemical failure (BCF) at 12 months. As the learning experience for sRALP increased operative time (OT) was significantly shorter (from 139.5 to 121 minutes) and the amount of nerve-sparing (NS) undertaken increased (from 46% to 80%). While complications rate remained stable, estimated blood loss (EBL) and radiographic anastomotic leaks (RAL) decreased through the groups (from 124 to 69 ml and 40% to 16,7%, respectively). BCF and continence rates at 12 months after sRARP were similar among groups (23-36% and 36,7-50%, respectively) and chance of potency rates tended to increase (from 3.3% to 16-23%) but was not statistically significant. In a multivariate analysis, predictors for BCF were PSM and GS 8-10. Non-radiation primary treatment was the unique predictor of continence at 12 months after sRARP. Our data may suggest a decreasing trend in terms of OT and EBL through the sRARP learning curve. While morbidity remained stable through the time, RAL trended towards a decline. A higher degree of NS was observed through the groups and there was a slight correlation trend between surgical expertise and potency recovery. PSM and GS 8-10 were predictors of BCF and non-radiation primary treatment predicted a better continence after sRARP.

The surgical learning curve for salvage robot-assisted radical prostatectomy: a prospective single-surgeon study.

Background To report the overall results and the learning curve (LC) in salvage robot-assisted radical prostatectomy (sRARP) patients, in terms of morbidity, oncological and functional outcomes in a single surgeon tertiary-referral center. Methods One hundred and twenty patients underwent sRARP by a single surgeon (V.P.) from 2008 to 2018. To assess the trends in the learning experience they were sub-divided in 4 groups of 30 consecutive patients based on date of surgery. The Kaplan- Meier method and regression models were used to identify survival estimations and predictors of potency, continence and biochemical failure (BCF) at 12 months. Results As the learning experience for sRALP increased operative time (OT) was significantly shorter (from 139,5 to 121 min) and the amount of nerve-sparing (NS) undertaken increased (from 46 to 80%). While complications rate remained stable, estimated blood loss (EBL) and radiographic anastomotic leaks (RAL) decreased through the groups (from 124 to 69 ml and 40% to 16,7%, respectively). BCF and continence rates at 12 months after sRARP were similar among groups (23-36% and 36,7-50%, respectively) and chance of potency rates tended to increase (from 3,3% to 16-23%) but was not statistically significant. In a multivariate analysis, predictors for BCF were PSM and GS 8-10. Non-radiation primary treatment was the unique predictor of continence at 12 months after sRARP. Conclusions Our data may suggest a decreasing trend in terms of OT and EBL through the sRARP learning curve. While morbidity remained stable through the time, radiographic anastomotic leaks trended towards a decline. A higher degree of NS was observed through the groups and there was a slight correlation trend between surgical expertise and potency recovery. PSM and GS 8-10 were predictors of BCF and non-radiation primary treatment predicted a better continence after sRARP.

Post-Treatment Biopsy Positivity In Prostate Cancer Patients Undergoing MpMRI-Targeted Radiation Dose Escalation

Radiation (RT) dose escalation improves prostate cancer outcomes; but, when the whole gland is treated to high doses, complication risk increases. We hypothesized that dose escalation to multiparametric MRI (mpMRI) defined dominant intraprostatic tumor volumes (mpMRIBoost) would improve tumor control without increasing toxicity. Incomplete tumor eradication via prostate biopsy 2-3 years after treatment is a known predictor of biochemical failure. Biopsy positivity was used to compare the efficacy of mpMRIBoost to that of standard whole gland RT (SRT) doses from an independent prospective randomized trial. Patients on three investigator initiated clinical trials incorporating mpMRIBoost who underwent planned prostate biopsies at 2.0-2.5 years after completing all treatment (n = 33) were eligible for inclusion. The biopsy positivity rate after mpMRIBoost was compared to that of a reference group treated with SRT doses (n = 115) to the whole prostate on a randomized single-institution hypofractionation clinical trial. At the time of endpoint biopsy, all included patients were without evidence of failure. Univariable and multivariable analysis (MVA) was performed using biopsy positivity, defined as adenocarcinoma with or without RT effect. Of those treated with mpMRIBoost: 3 (9%) were low, 25 (76%) intermediate, and 5 (15%) high risk. Assuming an α/β ratio of 1.5, mpMRIBoost patients received an equivalent dose (EQD2) of 76 Gy to the prostate, with focal dose escalation to an EQD2 of 98-122 Gy to the mpMRI lesions. Of those treated with SRT, 23 (20%) were low, 74 (64%) intermediate, and 18 (16%) high risk. The SRT patients received an EQD2 of 76 Gy (n = 64) or 84.24 Gy (n = 51; hypofractionation) to the prostate without boost. Median time from treatment to biopsy was 2 years (range, 1.6-3.3). Overall, the post-treatment biopsy results were negative in 51% (n = 76), atypical suspicious cells in 12% (n = 17), carcinoma with RT effect in 30% (n = 45) and frank carcinoma in 7% (n = 10). On MVA, dose escalation by mpMRIBoost decreased the odds of post-treatment positive biopsy by 9.7-fold (p = 0.0006), along with age below 70 by 2.5-fold (p = 0.038) and average biopsy core tumor volume (bTV) <20% by 3-fold (p = 0.015). The mpMRIBoost patients had no treatment-related grade 3 urinary or bowel complications. MRI-guided tumor dose escalation to an EQD2 of 98-122 Gy, with the remaining prostate receiving 76 Gy, was the strongest predictor of post-RT biopsy positivity without increased grade 3 toxicity. Post-RT prostate biopsy positivity has been significantly associated with distant metastasis and cancer-specific survival.Abstract 4025; TableMultivariable Analysis of Positive vs. Negative/Atypical Post-Treatment BiopsyOR (95% CI)pAge: <70 vs ≥700.41 (0.17, 0.95)0.038low vs. intermediate risk0.48 (0.17, 1.38)0.174low vs. high risk0.89 (0.16, 5.08)0.893bTV: ≤20% vs. >20%0.33 (0.14, 0.81)0.015ADT: yes vs. no0.43 (0.14, 1.27)0.125mpMRIBoost vs. SRT0.10 (0.03, 0.38)0.0006 Open table in a new tab

Treatment interruptions affect biochemical failure rates in prostate cancer patients treated with proton beam therapy: Report from the multi-institutional proton collaborative group registry

IntroductionTo date, no studies examining the effect of treatment interruptions (TI) with proton beam therapy (PBT) have been published. The goal of our study was to determine the predictors of TI amongst patients with prostate cancer (PCa) treated with PBT and to determine whether TI are associated with biochemical failure (BF). We hypothesized that any correlation between TI and biochemical control would be more pronounced in high risk groups. MethodsData for 4278 patients with PCa was obtained from the prospectively collected Proton Collaborative Group (PCG) data registry. Univariate and multivariate logistic regression analysis (MVA) was used to model possible predictors of BF. A subset analysis was performed for high risk patients treated with ADT and PBT. Finally, propensity score (PS) analysis was performed to account for any indication bias caused by lack of randomization. ResultsTotal treatment duration (OR, 1.05 [1.04–1.06]; p < 0.001) increased the likelihood of TI on MVA. TI did not have a statistically significant correlation with BF (OR, 1.44 [0.86–2.39]; p = 0.162) amongst PS matched patients. However, on subset analyses of high risk group patients with PS matching, there was a trend towards worse BF in patients with TI (OR 3.85; 95%CI (0.96–15.44); p = 0.057). ConclusionIn the first analysis of its kind, the results suggest that TI in high risk PCa patients treated with PBT and ADT have worse BF rates. Interventions such as increased patient education, proper maintenance of proton facilities, and decreasing total treatment duration with alternative fractionation schedules may help avoid the unintended negative effects on tumor control due to TI. However, future analyses on a larger patient population is needed.

Biopsy positivity in prostate cancer patients undergoing mpMRI-targeted radiation dose escalation.

336 Background: Radiation (RT) dose escalation improves prostate cancer outcomes, but when the whole gland is treated to high doses complications can arise. We used prostate multiparametric MRI (mpMRI) findings for targeted dose escalation (MTDE) in prospective clinical trials in which prostate biopsy at 2-3 years after completion of RT was planned. Biopsy positivity is a known predictor of biochemical failure. These findings are compared to those in another cohort in which standard whole gland RT doses were used. Methods: Patients enrolled on three investigator initiated clinical trials incorporating MTDE (n=30) were eligible for inclusion. All patients were assessed for response by prostate biopsy 2-3 years after RT. Patients were compared to a reference group treated with standard RT doses to the whole prostate on a randomized trial at Fox Chase Cancer Center (FCCC trial). Univariable and multivariable analysis (MVA) was performed to assess for correlation with biopsy positivity, defined as carcinoma with or without RT effect. Results: Of those treated with MTDE: 3 (10%) were low, 23 (77%) intermediate, and 4 (13%) high risk. Assuming an α/β ratio of 1.5, MTDE patients received an equivalent dose (EQD2) of 76 Gy to the prostate, with focal dose escalation to an EQD2 of 98-122 Gy to mpMRI lesions. The MTDE cohort was compared with 115 patients from the FCCC trial, where 23 (20%) were low, 74 (64%) intermediate, and 18 (16%) high risk. The FCCC trial patients received an EQD2 of 76 Gy (n=64) or 84.24 Gy (n=51) without boost. Median time from RT to biopsy was 2 years (range, 1.6-3.3). The post-treatment biopsy results were negative in 50% (n=73), atypical in 12% (n=17), carcinoma with RT effect in 31% (n=45) and frank carcinoma in 7% (n=10). On MVA, patients with tumor volume &gt;20% were more likely to have positive post-RT biopsies (OR: 3.21, 95% CI: 1.34-7.68, p= 0.009). MTDE patients were less likely to have positive post-RT biopsies, 10% vs. 45%, (OR: 0.13, 95% CI: 0.03-0.46, p=0.002). Conclusions: Focal dose-escalation to mpMRI-defined lesions significantly reduces biopsy positivity, a measure associated with long term outcomes including distant metastasis.

Determinants of biochemical failure and distant metastases-free survival in high-risk prostate cancer patients treated with external beam radiotherapy.

371 Background: Objectives were to1) identify predictors of biochemical failure(BCF) -free survival (FFS) &amp; distant metastases free-survival (DMFS) in high-risk prostate cancer (HRPC) patients treated with external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT); 2) assess the impact of nodal irradiation &amp; escalation of dose to the nodal volumes in HRPC. Methods: Between Feb 2000 &amp; May 2011, 462 patients with HRPC were treated with EBRT +/- ADT. This spanned an era of technical development; prior to 2002 conventional dose radiotherapy was routinely delivered, between 2002-2008, dose escalation to the prostate &amp; pelvic lymph nodes was undertaken in a phase II trial &amp; subsequently all patients were treated with a dose-escalated protocol. The disease characteristics included, a median PSA of 20ng/ml (range: 1-563), T3-T4 in 33% (n=158), &amp; Gleason grade group (GGG) 3-5 in 72% (n=331). The majority (n=405, 88%) received ADT with EBRT &amp; median duration of ADT was 36 months (range: 0-197). Dose escalated EBRT was utilized in 52% (n=241) &amp; nodal irradiation in 69% (n=317); escalation of dose to nodal volumes was performed in 20% (n=93). Results: The median follow-up was 8.7yrs (range: 0.9-18.9). Median nadir PSA was &lt; 0.05ng/ml (range: &lt;0.05-5.78) with median time to nadir (TTN) of 11 months (range: 2-130). Cumulative incidence rates of BCF at 5 and 10-yrs were 23% &amp; 45%; corresponding rates for DM were 6.6% &amp; 14%, respectively. The 5 &amp; 10-yr FFS rates were 75% &amp; 51%; corresponding DMFS rates were 91.5% &amp; 80%, respectively. On multivariate analysis, T stage (p&lt;0.001), GGG (p&lt;0.001), ADT (p=0.002), dose escalation to prostate (P=0.012) &amp; median nadir PSA (p&lt;0.001) were independent predictors of FFS. The GGG (p=0.007), median nadir PSA (p=&lt;0.001) &amp; Nodal RT (p=0.03) were independent predictors of DMFS. PSA of 20 &amp; TTN predicted neither FFS nor DMFS. Conclusions: Nadir PSA level was an independent predictor of FFS &amp; DMFS. Undetectable PSA level was associated with prolonged FFS &amp; DMFS. Dose escalation to prostate resulted in an improved FFS &amp; Nodal irradiation in an improved DMFS. Further studies are required to identify subgroups that may benefit the most from nodal irradiation.

The GP Score, a Simplified Formula (Bioptic Gleason Score Times Prostate Specific Antigen) as a Predictor for Biochemical Failure after Prostatectomy in Prostate Cancer

Objectives: We used a new GP score (Gleason score multiplied by prostate-specific antigen) without the T stage as a predictive value for biochemical failure (BCF) after prostatectomy. Materials and Methods: We assessed 459 prostate cancer patients who underwent prostatectomies at our institution. Three sub-groups were defined in terms of D'Amico classification risk (low, intermediate, and high) and Gleason score (low, < 50; intermediate, 50-100; and high GP score, > 100). Risk factors for BCF were evaluated by multivariate analysis with a Cox hazard model. A log-rank test was used to compare the BCF rate in the 2 groups. Results: There was nosignificant difference in the non-BCF rate between the lowrisk and low GP score subgroups or the intermediate risk andintermediate GP score subgroups. In contrast, the non-BCFrate of the high GP score subgroup (42.1%) was significantlylower than that of the high-risk subgroup (66.1%, log-rankp = 0.008). Based on multivariate analysis, a high GP score(p = 0.001; HR 3.78; 95%CI 1.95-7.35) was a significant independent risk factor for BCF after prostatectomy. Conclusion: The GP score, consisting of two absolute numbers, may be a valuable predictive factor for BCF after prostatectomy, especially in the high-risk failure group.

MON-561 Medullary Thyroid Cancer in a Single Institution: Factors Associated With Biochemical Failure

Background: Medullary thyroid carcinoma (MTC) is a rare thyroid cancer with a disproportionate high mortality and can be sporadic or familial. Surgery is the only potentially curative treatment. Our aim was to access demographic, clinical and pathological characteristics of MTC patients associated with biochemical failure after surgery. Methods: Retrospective observational study of patients with MTC diagnosed between 1984 and 2018 and followed-up in our institution. Results: We evaluated 76 individuals with MTC, 27.6% with hereditary MTC, 69.7% female, median of age 49 years-old (IQR 33.50-60.00). The median of preoperative calcitonin levels was 1121 pg/mL (IQR 445-4383), being ≥500 pg/mL in 72.3%. Preoperative calcitonin levels, when performed, had a sensitivity of 97.9%. According to TNM staging (AJCC 8th ed.), 35.9% were in stage I, 15.6% in stage II, 1.6% in stage III and 46.9% in stage IV. One patient had poor functional status, contraindicating surgery. A total of 75 patients were submitted to thyroidectomy (or completion thyroidectomy when indicated) with lymph node dissection at our institution (n=50) or an outside one (n=25). Biochemical cure (BC) was achieved in 48 (64%) patients after surgery; of these, 7 (14.58%) relapsed. BC was 95.7% in stage II, 100% in stages II/III and 24.1% in stage IV (p<0.001). Biochemical failure occurred in 36% of patients, all of them with preoperative calcitonin levels ≥500 pg/mL (p<0.001). There were no significant differences in sex, age, presence of germline RET mutation and results of fine-needle aspiration cytology between groups. Regarding histological features, patients with biochemical failure had higher tumor size (2.5 cm vs. 1.9 cm, p=0.025), multifocality (66.7% vs. 37.5%, p=0.024), vascular invasion (76.5% vs. 43.8%, p=0.028), perineural invasion (23.4 % vs. 0%, p=0.024), capsular invasion (82.4% vs. 12.1%, p<0.001), extrathyroidal extension (57.9% vs. 7.9%, p<0.001), surgical margin positivity (57.9% vs. 7.9%, p<0.001) and lymph node positivity (100% vs. 33.3%, p<0.001). Preoperative calcitonin levels (OR per increments of 500 pg/mL=1.183; p=0.012), tumor size in cm (OR=2.093; p=0.003), multifocality (OR=2.769; p=0.049), vascular invasion (OR=4.250; p=0.024), capsular invasion (OR=27.000; p<0.001), extrathyroidal extension (OR=85.000; p<0.001), surgical margins positivity (OR=17.455; p=0.001) and lymph nodes positivity (OR=62.500; p<0.001) were predictors of biochemical failure. The 5-year survival rate was higher in the BC group (91.7% vs. 74.1%; p=0.049). Conclusions: Several tumor histological characteristics were the best predictors for biochemical failure and preoperative calcitonin level was the only significant predictor performed before surgery. Demographic data, RET mutation and cytology were not associated with BC. These findings highlight that early detection is important to achieve BC in MTC.

Early predicting factor for biochemical failure for patients with intermediate and high-risk prostate cancer treated by definitive radiotherapy.

52 Background: The prostate-specific antigen nadir (nPSA), a strong prognostic factor for prostate cancer, does not occur until several years after definitive radiotherapy. Our aim was to assess an early predictive factor for biochemical failure (BCF) in patients with intermediate- and high-risk prostate cancer treated with definitive radiotherapy. Methods: Between 2007 and 2017, 97 patients with localized prostate cancer underwent radiotherapy at two institutions. We used a pelvic lymph node involvement risk of 15% as the cutoff value, calculated using the Roach formula, to decide whether to deliver prostate and seminal vesicle only radiotherapy (PORT) or whole-pelvis radiotherapy (WPRT). Twenty-seven patients (27.8%) underwent PORT with the prostate receiving 45 Gy (4.5 Gy per fraction) and the other 70 patients (72.2%) underwent WPRT with the prostate receiving 72 Gy (2.4 Gy per fraction). The median equivalent dose in 2 Gy fractions to the prostate was 80.3 Gy based on the assumption that the α/β ratio is 1.5 Gy. Sixty-two patients (63.9%) were treated with androgen deprivation therapy (ADT). Results: The median follow-up time was 40 (range, 10 to 133) months. The 4-year BCF-free survival (BCFS) rate was 87.0%. In the univariate analysis, the nPSA, the nPSA within 12 months (nPSA12), and ADT use were significant predictive factors for BCF. nPSA ( p = 0.003) and ADT use ( p = 0.041), but not nPSA12 ( p = 0.485), were independent predictive factors for BCF in the multivariate analysis. However, there was a strong correlation between nPSA and nPSA12 in this study ( r = 0.854, p &lt; 0.001). The receiver operating characteristic curve identified 0.47 ng/ml as the optimal cutoff value of nPSA12 for predicting BCF. The 4-year BCFS rate in patients with nPSA12 &lt; 0.47 ng/ml was 100% in contrast to 71.3% in patients with nPSA12 ≥ 0.47 ng/ml. Conclusions: The nPSA12 has a strong correlation with nPSA and is a considerable predictor of BCF. Therefore, the treatment outcome can be predicted early using nPSA12. Furthermore, ADT can significantly reduce BCF in patients with intermediate- and high-risk prostate cancer.

Long-Term Prostate Specific Antigen Stability and Predictive Factors of Failure after Permanent Seed Prostate Brachytherapy.

Defining biochemical failure as nadir + 2 may overestimate cure after radiotherapy. We assessed long-term prostate specific antigen stability after low dose rate prostate brachytherapy and predictors of biochemical failure when prostate specific antigen was slowly rising below the nadir + 2 ng/ml threshold. A total of 2,339 patients with low or intermediate risk prostate cancer received 125iodine brachytherapy from 1998 to 2010 with a minimum 3-year followup. In addition, 49.7% of the patients received 6 months ofandrogen deprivation. Clinical, dosimetric and prostate specific antigen data were retrieved from a prospective database. Biochemical results were classified as stable or rising prostate specific antigen (0.2 ng/ml or greater and increased 0.1 ng/ml or greater during the preceding 2 years), or biochemical failure (defined as nadir + 2). Multivariate analysis was done to identify predictors of failure used to create logistic regression models. At a median followup of 89 months (range 37 to 199) prostate specific antigen was stable (nadir 0.03 ng/ml and at 60 months 0.04 ng/ml) in 2,004 patients (86%) and rising (nadir 0.16 ng/ml and at 60 months 0.29 ng/ml) in 145 (6%) while biochemical failure (nadir 0.51 ng/ml, p <0.001) was noted in 190 (8%). When there was no prior androgen deprivation therapy, the prostate specific antigen nadir and prostate specific antigen at 60 months were the strongest predictors of failure (OR 20.6 and 18.3, respectively, each p <0.0001). The logistic regression model had 85% sensitivity and 98% specificity, and predicted failure in 8 of 82 men (9.8%). A second model was created for the group with androgen deprivation therapy and rising prostate specific antigen using the predictive factors prostate specific antigen at 60 months (OR 53.9, p <0.0001) and T stage (OR 0.25, p = 0.0008). This model predicted biochemical failure in 30 of 56 men (54%) with 85% sensitivity and 93% specificity. The 2 predictive models yield an anticipated 90% cure rate in the entire cohort. Brachytherapy is highly curative with stable prostate specific antigen at a surgical ablation level in 86% of patients. Rising prostate specific antigen is rare at a 6% incidence and often innocuous.

Outcome of radical prostatectomy in primary circulating prostate cell negative prostate cancer.

IntroductionAround 90% of prostate cancers detected using the serum prostate specific antigen (PSA) as a screening test are considered to be localised. However, 20–30% of men treated by radical prostatectomy experience biochemical failure within two years of treatment. The presence of primary circulating prostate cells (CPCs) in the blood of these men implies a dissemination of the tumour and could indicate a greater risk of treatment failure.ObjectiveTo evaluate the use of the number of primary CPCs detected before surgery in the prediction of biochemical failure at ten years.HypothesisThe dissemination of cancer cells to distant sites will determine the patient’s prognosis. The absence of primary CPCs in men undergoing radical prostatectomy for prostate cancer may imply a less aggressive disease and therefore could be utilised as a prognostic factor to predict biochemical failure after surgery.Methods and patientsA single-centre observational study of a cohort of 285 men who underwent radical prostatectomy as monotherapy for prostate cancer, in whom the number of CPCs prior to treatment was determined, and who were followed up for ten years to determine biochemical failure. A Cox proportional risks with polynomial fractions analysis was used to predict biochemical failure based on the number of primary CPCs detected. A decision curve analysis was performed for the model obtained.ResultsKaplan–Meier curves for biochemical free survival at ten years was 47.34% (95% CI 38.71–55.48%). It is important to note that in CPC negative men, the ten years Kaplan–Meier biochemical-free survival was 90.35% (95% CI 75.0–96.27) whereas in men who were primary CPC positive, the biochemical free survival rate was 30.00% (95% CI 20.34–40.60%).The Coxs´model to predict biochemical failure using transformed data with a power of minus one for the number of primary CPCs detected, showed a Harrell´s C concordance index of 0.74 and a decision analysis curve showing a net benefit of CPC detection over other risk factors to predict biochemical failure.ConclusionsThe number of primary CPCs detected before surgery permits a good prediction of subsequent biochemical failure in men undergoing radical prostatectomy as monotherapy for prostate cancer. Men negative for primary CPCs have a biochemical-free survival of over 90% at ten years and should be considered for curative surgery.

Development and internal validation of a multivariable prediction model for biochemical failure after whole-gland salvage iodine-125 prostate brachytherapy for recurrent prostate cancer

BackgroundLocalized recurrent prostate cancer after primary radiotherapy can be curatively treated using salvage iodine-125 (125I) brachytherapy. Selection is hampered by a lack of predictive factors for cancer control. This study aims to develop and internally validate a prognostic model for biochemical failure (BF) after salvage 125I brachytherapy. Methods and MaterialsWhole-gland salvage 125I brachytherapy patients were treated between 1993 and 2010 in two radiotherapy centers in the Netherlands. Multivariable Cox regression was performed to assess the predictive value of clinical parameters related to BF (Phoenix-definition [prostate-specific antigen [PSA]-nadir + 2.0 ng/mL]). Missing data were handled by multiple imputation. The model's discriminatory ability was assessed with Harrell's C-statistic. Internal validation was performed using bootstrap resampling (2000 data sets). Goodness-of-fit was evaluated with calibration plots. All analyses were performed using the recently published TRIPOD (Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) statement. ResultsAfter median followup of 74 months (range 5–138), 43 of a total 62 patients developed BF. In multivariable analysis, disease-free survival interval (DFSI) after primary therapy and pre-salvage prostate-specific antigen doubling time (PSADT) were predictors of BF: corrected hazard ratio (HR) 0.99 (95% confidence interval 0.97–0.999; p = 0.04) and 0.94 (95% confidence interval 0.89–0.99; p = 0.03), both for a 1-month increase (optimism-adjusted C-statistic 0.70). Calibration was accurate up to 36 months. Of patients with PSADT >30 months and DFSI >60 months, 36-month biochemical disease-free survival was >75%. Every 12-month increase in DFSI will allow 3-month decrease in PSADT while maintaining the same biochemical recurrence-free rates. ConclusionsWe have presented results from a cohort of patients undergoing salvage 125I-brachytherapy. Our data show that better selection of patients is possible with the DFSI and PSADT.

Prostate brachytherapy as salvage for local failure after external beam radiation.

125 Background: Local failure (LF) after external beam radiation (EBRT) for prostate cancer is a serious problem. Most patients receive non-curative androgen deprivation therapy (ADT), but there is a subset with LF who are still potentially curable. There is limited evidence to suggest that prostate brachytherapy (BT) is an effective, potentially curative salvage therapy with acceptable toxicity. We hypothesize that salvage BT following EBRT can achieve high rates of biochemical control with acceptable toxicity. Methods: We analyzed 39 consecutive patients treated from 1998-2013 with salvage BT at 2 centers. All patients had pathologically confirmed LF following previous EBRT without distant mets &amp; a disease-free interval of ≥ 18-24 mo. Salvage BT to the whole prostate was delivered to 29 patients using low-dose rate I-125 or Pd-103 seed implants (median dose 100 Gy with Pd-103) while 10 received HDR BT (median 30 Gy in 6 fractions). Cases were planned as if de novo but to a lower dose. 33 (85%) received neoadjuvant and/or adjuvant ADT as part of their salvage therapy. Biochemical failure (BF) was defined using the Phoenix criteria. Risk factor analysis was conducted to identify characteristics that predict BF after salvage BT. Results: For the 39 patients, median PSA at diagnosis was 8.4, and 21 (54%) had high-risk disease. Median EBRT dose was 70 Gy with 11 patients (28%) receiving ADT. Median PSA nadir following EBRT was 0.8 (range 0 – 2.6). Median time to recurrence was 53 mo (range 18 – 150), and median pre-salvage PSA was 4.8. Median follow-up after salvage BT was 60.1 mo (range 7 – 150). Biochemical failure-free survival, DMFS and OS at 5 &amp; 7 yrs were 76% &amp; 67%; 91% &amp; 85% and 92% &amp; 84%, respectively. On univariate analysis, PSA nadir after EBRT &amp; pre-salvage PSA were significant predictors of BF (p&lt; 0.01 for both). On multivariate analysis, only pre-salvage PSA was a significant independent predictor of BF (p&lt; 0.01). Freedom from late grade 3 GU toxicity at 3 yrs was 83%. There were no late Grade 3 GI toxicities. Conclusions: This is the largest series reporting on salvage prostate brachytherapy plus ADT for local-only failures after EBRT &amp; suggests that salvage BT with ADT offers selected patients prolonged disease-free survival with acceptable toxicity.

Genomic predictors of biochemical failure following radical prostatectomy.

114 Background: Although clinical correlates can help predict biochemical failure (BF), genomic correlates have yet to be identified. We hypothesized there would exist genomic profiles in patients who experience BF after radical prostatectomy (RP), for whom aggressive regional therapy may be more appropriate. Methods: Genes of interest were identified using the 25 most commonly mutated genes from the COSMIC dataset. The Cancer Genome Atlas (TCGA) was used to study normalized microarray gene expression data for patients who underwent RP for treatment of Gleason 7-10, T1/T2 N0 prostate adenocarcinoma. BF was considered PSA &gt; 0.1 following prostatectomy. Clinical data of interest included age, pre-treatment PSA, Gleason score, pathologic T stage, and country of origin. A multi-level hierarchical logistic regression model clustered with random effects by pathologic T stage and country of origin was built to identify predictors of BF. Variances were used to estimate how genomic differences explained differences in BF. Results: We identified 296 patients with T1/T2 N0 prostate adenocarcinoma who underwent RP. Median age was 60 with a median follow up of 2.3 years. 59% (n = 177) had Gleason 7 disease and 54% (n = 154) had T1 disease. 40.8% (n = 121) of patients had BF following RP. After adjusting for clinical covariates, 4 genes were associated with differences in BF. Specifically, increased RNA expression of E2F3 (OR 1.11 p &lt; .001), CTNNB1 (OR 1.49, p = .002), and AR (OR 1.21, p &lt; .001) were seen in patients who experienced BF. Expression of TP53 (OR 0.75, p &lt; .001) and Gleason 7 disease (OR 0.62 vs. Gleason 8-10, p &lt; .001) were associated with decreased likelihood of BF. Clustering by pathologic T stage accounted for 10% of variance in BF indicating that the 4 genes augment clinical patient characteristics. Conclusions: Genomic data augments pre-treatment clinical data in the stratification of patients undergoing RP. RNA expression of E2F3, CTNNB1, AR and TP53 is associated with differences in BF following RP. Clinically, these genes could aid in identifying patients who may benefit from more aggressive therapy. Further studies of the relationship between these genes and the development of prostate cancer could aid in future targeted therapies.

Genomic Predictors of Biochemical Failure Following Radical Prostatectomy

Genomic Predictors of Biochemical Failure Following Radical Prostatectomy

Predictors of Biochemical Failure Following Radical Prostatectomy With Positive Surgical Margins

Background:: Radical prostatectomy is an established treatment modality for prostate cancer. Following radical prostatectomy, patients with positive surgical margins have increased risk of biochemical, and subsequently, clinical relapse. However, not all patients with positive margins will suffer disease recurrence. The aim of this study was to assess the factors that might predict the higher risk of disease recurrence in prostate cancer patients with positive surgical margins. Objectives:: The aim of this study was to assess the factors that might predict the higher risk of disease recurrence in prostate cancer patients with positive surgical margins. Patients and Methods:: From March 2009 till October 2013, seventy seven patients who had pathologically proven positive surgical margins after radical prostatectomy were followed and serum PSA levels were measured every three months. In case of biochemical failure, they were treated with salvage radiotherapy. Apart from pre-op and serial post-op PSA levels, number of positive margins based on anatomical classification of prostate, lymphovascular and perineural invasion, Gleason score and T-stage of the cancer were documented accurately. Results:: Fifty one patients (66.2%) had a single positive margin, while 26 (33.8%) had multiple positive margins. Among all 77 patients, 67 (87%) had biochemical failure. Cox regression analysis showed that among various parameters, only pre-op PSA>20ng/ml and having more than one positive margins were able to predict the likelihood of biochemical failure in the patients; while Gleason score, perineural invasion and lymphovascular invasion did not seem to have an important role in this regard. Conclusions:: Among patients with positive surgical margins after radical prostatectomy, those with pre-op PSA>20ng/ml or more than one positive margins are at greater risk of biochemical or/and clinical failure. In these patients, starting salvage radiotherapy after surgery might be considered as a logic option.

MP83-12 SALVAGE ROBOT-ASSISTED RADICAL PROSTATECTOMY FOR RECURRENT PROSTATE CANCER.

INTRODUCTION AND OBJECTIVES: To report short-term cancer control, functional and perioperative outcomes in a multi-institutional cohort of salvage robot-assisted radical prostatectomy (sRARP). METHODS: We retrospectively reviewed the records of 88 consecutivemenwho underwent sRARP, from July 2007 to June 2014, at 2 high-volume reference centers in the US. Failed primary therapy was: external beam radiotherapy (49%); brachytherapy (35%); HIFU (5%); cryoablation (9%) and others (2%). The endpoints were biochemical failure (BF), positive surgical margins (PSM), 30-day post-operative complications (POC), urinary continence (UC) and erectile function (EF). BF was defined as a PSA>0.2 ng/ml. UC and EF were defined as the use of 0padandSHIMscore>21, respectively. POCwere classifiedandgraded using the Clavien system. Kaplan-Meier method was conducted to estimate survivals for BF and exploratory univariate analysis and multivariable Cox regression for predictors of BF. Statistical significant if p<0.05. RESULTS: The mean (SD) patients’ age and PSA were 66 (7.5) years and 6.7 (7.8) ng/ml. Biopsy Gleason score was 6 (25%), 7 (39%), and 8 (36%). Clinical stage was cT1 (63%), cT2 (34%) and cT3 (4%). Mean (SD) estimated blood loss was 118 (61) ml and operative time was 166 (58) min. Mean (SD) length of hospital stay was 2.3 (3.7) days. There was no conversion to open approach. There was one (1%) intra-operative complication (rectal injury). Low grade (I-II) POC occurred in 7 (8%), high grade (III-IV)POC in4 (4%)and leakoncystogram in8 (9%)patients. PSM occurred in 17 (20%) patients. Pathology showed Gleason 8 in 52%, stage pT3 in 51%andpN1 in14%of the patients. In amedian (range) of 13 months (1-60 mon), BF occurred in 25 (28%) patients with a BF free-survival of 71%, 63% and 59% in 1, 2 and 3 years, respectively. No patient died. On univariate analysis pre-operative PSA, biopsy and pathology Gleason, cT and pT stage, and pN1 were predictors for BF. On multivariable analysis pre-operative PSA and pathology Gleason were independent predictors for BF. UC and EF were achieved in 48% and 11% within 1-year followup, respectively.Themain limitation is retrospectiveanalysis. CONCLUSIONS: To our knowledge, this is the largest cohort of sRARP demonstrating safety and feasibility. Operative time, perioperative morbidity, short-term cancer control and functional outcomes are acceptable and appear improved relative to historical data. This population remainsclinically challengingwithmajorityhaving local advanceddiseaseon final pathology. Gleason and PSA are independent predictors for BF.