Biochemical Failure In Patients Research Articles

Development of risk-score model in patients with negative surgical margin after robot-assisted radical prostatectomy

A total of 739 patients underwent RARP as initial treatment for PCa from November 2011 to October 2018. Data on BCR status, clinical and pathological parameters were collected from the clinical records. After excluding cases with neoadjuvant and/or adjuvant therapies, presence of lymph node or distant metastasis, and positive SM, a total of 537 cases were eligible for the final analysis. The median follow-up of experimental cohort was 28.0 (interquartile: 18.0–43.0) months. We identified the presence of International Society of Urological Pathology grade group (ISUP-GG) ≥ 4 (Hazard ratio (HR) 3.20, 95% Confidence Interval (95% CI) 1.70–6.03, P < 0.001), lymphovascular invasion (HR 2.03, 95% CI 1.00–4.12, P = 0.049), perineural invasion (HR 10.7, 95% CI 1.45–79.9, P = 0.020), and maximum tumor diameter (MTD) > 20 mm (HR 1.9, 95% CI 1.01–3.70, P = 0.047) as significant factors of BCR in the multivariate analysis. We further developed a risk model according to these factors. Based on this model, 1-year, 3-year, and 5-year BCR-free survival were 100%, 98.9%, 98.9% in the low-risk group; 99.1%, 94.1%, 86.5% in the intermediate-risk group; 93.9%, 84.6%, 58.1% in the high-risk group. Internal validation using the bootstrap method showed a c-index of 0.742 and an optimism-corrected c-index level of 0.731. External validation was also carried out using an integrated database derived from 3 other independent institutions including a total of 387 patients for the final analysis. External validation showed a c-index of 0.655. In conclusion, we identified risk factors of biochemical failure in patients showing negative surgical margin after RARP and further developed a risk model using these risk factors.

Multiparametric MRI as a Predictor of PSA Response in Patients Undergoing Stereotactic Body Radiation (SBRT) Therapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> In order to maximize the therapeutic ratio, it is important to identify adverse prognostic features in men with prostate cancer, especially amongst those with intermediate risk disease, which represents a heterogeneous group. These men may benefit from treatment intensification. Prior studies have shown pretreatment mpMRI may predict biochemical failure in patients with intermediate and/or high-risk prostate cancer undergoing conventionally fractionated external beam radiotherapy and/or brachytherapy. This is the first study to evaluate pretreatment mpMRI findings as a marker for outcome in patients undergoing SBRT. <h3>Materials/Methods</h3> We identified all patients treated at our institution with linear accelerator-based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) from November 2015 to March 2021. All patients underwent SpaceOAR placement followed by pre-treatment MRI. Post-treatment PSA measurements were obtained 4 months after SBRT, followed by every 3-6 months thereafter. A two-sample t-test was used to compare preoperative mpMRI features with clinical outcomes. <h3>Results</h3> 123 men were included in the study. The table below summarizes the pretreatment patient characteristics. Patients with higher pretreatment diameter of the largest intraprostatic lesion, number of prostate lesions, and maximal PI-RADS score were associated with higher PSA nadir and longer time to PSA nadir (p<0.0001). When separated by ADT treatment, this association remained for patients who were not treated with ADT (p<0.001). In patients who received ADT, the pretreatment MRI variables were each significantly associated with time to PSA nadir (p<0.01) but not with PSA nadir (p>0.30). <h3>Conclusion</h3> Our experience shows a significant association between mpMRI features and PSA outcome in patients treated with SBRT with or without ADT. Since PSA nadir has been shown to correlate with biochemical failure, this information may help radiation oncologists better counsel their patients regarding outcome after SBRT and can help inform future studies regarding who may benefit from treatment intensification with, for example, ADT and / or boost to dominant intraprostatic lesion.

Refining the definition of biochemical failure in the era of stereotactic body radiation therapy for prostate cancer: The Phoenix definition and beyond

Background and purposeThe Phoenix definition for biochemical failure (BCF) after radiotherapy uses nadir PSA (nPSA) + 2 ng/mL to classify a BCF and was derived from conventionally fractionated radiotherapy, which produces significantly higher nPSAs than stereotactic body radiotherapy (SBRT). We investigated whether an alternative nPSA-based threshold could be used to define post-SBRT BCFs. Materials and methodsPSA kinetics data on 2038 patients from 9 institutions were retrospectively analyzed for low- and intermediate-risk PCa patients treated with SBRT without ADT. We evaluated the performance of various nPSA-based definitions. We also investigated the relationship of relative PSA decline (rPSA, PSA18month/PSA6month) and timing of reaching nPSA + 2 with BCF. ResultsMedian follow-up was 71.9 months. BCF occurred in 6.9% of patients. Median nPSA was 0.16 ng/mL. False positivity of nPSA + 2 was 30.2%, compared to 40.9%, 57.8%, and 71.0% for nPSA + 1.5, nPSA + 1.0, and nPSA + 0.5, respectively. Among patients with BCF, the median lead time gained from an earlier nPSA + threshold definition over the Phoenix definition was minimal. Patients with BCF had significantly lower rates of early PSA decline (mean rPSA 1.19 vs. 0.39, p < 0.0001) and were significantly more likely to reach nPSA + 2 ≥ 18 months (83.3% vs. 21.1%, p < 0.0001). The proposed criterion (rPSA ≥ 2.6 or nPSA + 2 ≥ 18 months) had a sensitivity and specificity of 92.4% and 81.5%, respectively, for predicting BCF in patients meeting the Phoenix definition and decreased its false positivity to 6.4%. ConclusionThe Phoenix definition remains an excellent definition for BCF post-SBRT. Its high false positivity can be mitigated by applying additional criteria (rPSA ≥ 2.6 or time to nPSA + 2 ≥ 18 months).

Working Towards a New Definition of Biochemical Failure in the Era of Stereotactic Body Radiation Therapy for Prostate Cancer

Since the seminal Phoenix definition (nadir PSA+2) of biochemical failure (BCF) was published in 2006, increasingly more patients with low- and intermediate-risk prostate cancer (PCa) are being treated with stereotactic body radiation therapy (SBRT). Since SBRT leads to lower nadir PSA (nPSA) compared to conventionally fractionated RT, we investigated if an earlier nPSA+threshold can be used as an alternative definition of BCF.PSA kinetics from 9 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2003 to 2018. Patients received 35 to 40 Gy in 5 fractions, 38 Gy in 4 fractions or 26 Gy in 2 fractions (EQD23 Gy = 70-95 Gy) per institutional standards. Cox multivariable regression model was used to determine the adjusted association of relative change in PSA kinetics with biochemical relapse-free survival (BRFS) and association of BCF with time to nadir+2.A total of 2061 patients were included. Median follow-up was 71.9 months (interquartile range [IQR], 41.2-96.0). BCF occurred in 140 (6.8%) of patients. Median nPSA was 0.16 ng/mL, median time to nPSA was 48 months. Sensitivity of Phoenix definition for BCF was 93%, compared to 96%, 100%, and 100% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. False positive rate of Phoenix definition was 30%, compared to 41%, 58%, and 71% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. In patients who developed BCF, lead time gained from an earlier nPSA+threshold definition compared to Phoenix definition was 6 (IQR 0-15.3), 0 (IQR 0-11.3), 0 (IQR 0-0) months for nPSA+0.5, nPSA+1.0 and nPSA+1.5, respectively. Relative change in PSA between 6 months and 18 months after treatment was significantly associated with BRFS (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.28-2.34, P < 0.0004). Among the 30% patients who had a false call of BCF due to PSA bounce, 48 (84.2%) reached nPSA+2 in ≤18 months, and 9 (15.8%) in > 18 months. In patients who had BCF, 27 (19.3%) reached nPSA+2 in ≤18 months, and 113 (80.7%) in > 18 months. Median time to nPSA+2 was significantly longer in patients with BCF (41 vs. 12 months, P < 0.002). BCF is associated with longer time to nPSA+2 (HR 0.13, 95% CI 0.09-0.20, P < 0.002).A lower nadir-based threshold provides minimal increase in sensitivity at the cost of a higher false positive rate and does not provide a clinically relevant lead time benefit for a pending BCF in patients with low- to intermediate-risk PCa undergoing SBRT. A rate-of-change based metric in the first 18 months post-SBRT is significantly associated with BRFS. Patients who have an early PSA bounce after SBRT rarely develop a true BCF and true BCF tends to happen later (> 18 months). Phoenix definition remains a valuable tool in the SBRT era. BCF should not be prematurely called which runs the risk of high rates of false positivity.

Clinical predictors for biochemical failure in patients with positive surgical margin after robotic-assisted radical prostatectomy.

Patients with positive surgical margins (PSMs) after radical prostatectomy for localized prostate cancer have a higher risk of biochemical failure (BCF). We investigated the risk factors of BCF in patients with PSMs after robotic-assisted radical prostatectomy (RARP). We evaluated 462 patients who underwent RARP in a single medical center from 2006 through 2013. Of them, 61 with PSMs did not receive any treatment before BCF. Kaplan-Meier curve and Cox regression analysis were used to compare patients with (n = 19) and without (n = 41) BCF. Overall, 13.2% of patients had PSMs, and of those, 31.7% experienced BCF during follow-up. The mean follow-up duration was 43.7 months (42.4 [non-BCF] vs 46.35 (BCF], p = 0.51). In univariant analyses, the platelet to lymphocyte ratio (6.26 [non-BCF] vs 8.02 [BCF], p = 0.04) differed statistically. When patients were grouped by pathologic grade ≦2 or ≧3 (p = 0.004), the BCF-free survival rates differed significantly. Seminal vesicle invasion also differed significantly (5 [non-BCF] vs 7 [BCF], p = 0.005). Patients with undetectable nadir prostate-specific antigen (PSA) after RARP (BCF rate 4/34) differed statistically from those with detectable PSA after RARP (BCF rate 15/26) (p < 0.001). In the multivariate analysis, the platelet/lymphocyte (P/L) ratio, pathologic grade, and undetectable nadir PSA remained statistically significant. In patients who undergo RARP and have PSMs, P/L ratio >9 preoperatively, pathologic grade ⩾3, and detectable nadir PSA after RARP should be considered adverse features. Early intervention such as salvage radiation therapy or androgen deprivation therapy should be offered to these patients.

Postoperative Biochemical Failure in Patients With PI-RADS Category 4 or 5 Prostate Cancers: Risk Stratification According to Zonal Location of an Index Lesion

OBJECTIVE. The objective of our study was to assess postoperative biochemical failure in patients with prostate cancer according to zonal location of an index lesion classified as Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) category 4 or 5. MATERIALS AND METHODS. Consecutive patients (n = 232) with prostate cancer who had PI-RADSv2 category 4 or 5 lesions on MRI and who underwent radical prostatectomy were retrospectively evaluated. We investigated clinical (prostate-specific antigen density), MRI (PI-RADSv2 category of index lesion and zonal location, assessed as peripheral zone [PZ] or transition zone [TZ], of index lesion), and pathologic (tumor volume, tumor grade, and presence of extraprostatic extension) parameters. We analyzed Kaplan-Meier survival curves and the Cox proportional hazards model to assess 2-year biochemical failure-free survival and identify significant parameters associated with postoperative biochemical failure RESULTS. Biochemical failure occurred in 14.2% of patients (33/232). Two-year biochemical failure-free survival of patients with a PI-RADSv2 category 4 or 5 index lesion was 81.3%. For all patients, 2-year biochemical failure-free survival was different according to PI-RADSv2 category (category 4, 86.4%; category 5, 74.5%; p = 0.021) or zonal location (PZ, 75.3%; TZ, 96.8%; p = 0.003). Two-year biochemical failure-free survival in patients with category 4 lesions was similar in patients with PZ lesions (83.1%) and those with TZ lesions (100.0%) (p = 0.072), whereas it was different in patients with category 5 lesions (PZ, 62.0%; TZ, 95.0%; p = 0.002). In multivariate analysis, only zonal location of an index lesion on MRI was associated with biochemical failure (hazard ratio = 0.155; p = 0.012). CONCLUSION. Zonal location of an index lesion on MRI may be a useful imaging bio-marker to predict postoperative biochemical failure.

Minimal Residual Disease Defines the Risk and Time to Biochemical Failure in Patients with Pt2 and Pt3a Prostate Cancer Treated With Radical Prostatectomy: An Observational Prospective Study.

To compare Gleason score (GS), pathological stage, minimal residual disease (MRD) and outcome after prostatectomy radical for prostate cancer. 290/357 men with GS 6 or 7 and pT2 or pT3a disease treated with radical prostatectomy participated. Blood and bone marrow were obtained one month after surgery. Circulating prostate cells (CPCs) were detected using differential gel centrifugation and immunocytochemistry with anti PSA, micro-metastasis weas detected using immunocytochemistry with anti-PSA. Biochemical failure free survival (BFFS) and restricted mean survival times (RMST) were calculated according to GS and stage. MRD was classified as negative, patients only positive for micro-metastasis and patients positive for CPCs; BFFS and RMST were calculated according to MRD sub-type. GS7 (HR 3.03) and pT3a (HR 3.68) cancers were associated with a higher failure rate, shorter time to failure and associated with CPC positive MRD (p < 0.001), while G6 and pT2 with MRD negative disease (p<0.001). Men with CPC (+) MRD were at high risk of early treatment failure; 15% BFFS at 10 years, RMST 3.0 years. Men positive for only micro-metastasis were at risk of late failure, 50% BFFS at 10 years, RMST 8.0 years compared with MRD negative patients; 80% BFFS at 10 years, RMST 9.0 years. The sub-type of MRD identifies Gleason 6 pT2 patients with a poor prognosis and Gleason 7 pT3a patients with a good prognosis and could be used to classify men according to personal risk characteristics for the use of adjuvant treatment.

A Phase III Multi-Centre Randomised Trial comparing adjuvant versus early salvage Radiotherapy following a Radical Prostatectomy: Results of the TROG 08.03 and ANZUP “RAVES” Trial

Adjuvant radiotherapy (ART) has been shown to nearly halve the risk of biochemical failure (BF) for high risk post prostatectomy patients. The RAVES trial aimed to test the hypothesis that observation with early salvage radiotherapy (SRT) is not inferior to ART with respect to biochemical failure in patients with high risk disease after radical prostatectomy (RP). Eligible patients needed to have either extraprostatic extension, seminal vesicle invasion (SVI) or positive surgical margins (PSM) and have a postoperative PSA ≤0.10ng/ml. Patients were randomised 1:1 to either ART commencing within 6 months of RP or close observation with early SRT triggered by a PSA level of ≥0.20ng/ml. RT plans were reviewed in real time and utilised 3D CRT or IMRT/VMAT to a dose of 64Gy/32# to the prostate bed alone without androgen deprivation (AD). Primary aim was to exclude a 10% inferiority in Freedom from Biochemical Failure (FFBF) in the SRT arm corresponding to 5-year FFBF rates of 74% (ART) and 64% (SRT) and a hazard ratio (HR) of 1.48. BF was defined as a PSA rise to 0.40 or higher or commencement of AD after RT. Analysis was on an intention to treat basis. 333 patients were randomised (n=166 ART; n=167 SRT) across 32 institutions in Australia and New Zealand between March 2009 and December 2015. Median follow up was 6.1 years. The Independent Data Monitoring Board recommended that enrolment close early based on interim analyses showing that further recruitment to reach the target of 470 was unlikely to substantially increase power due to an unexpectedly low event rate. Mean age in both arms was 63 years. 16% in ART had a high Gleason Score (8-10) compared with 15% in SRT. SVI was seen in 19% of ART and 20% with SRT. PSM occurred in 66% of ART and 68% of the SRT groups. 84 SRT patients (50.3%) had their PSA rise to 0.2, triggering SRT, of which 80 received SRT. The 5 year FFBF rates were 86% (95% CI [79%, 91%]) in the ART arm compared with 88% (95% CI [82%, 92%]) in the SRT arm. The 8 year rates were 79% with ART (95% CI [68%, 87%]) and 76% (95% CI [65%, 84%]) with SRT. The hazard ratio for the SRT arm was 1.03 (90% CI [0.65, 1.63], p=0.91). The corresponding 90% range in absolute difference between SRT and ART at 5 years was from SRT 5.8% inferior to SRT 5.1% superior. Six percent of patients in the ART arm developed evidence of local, regional or distant failure by 8 years compared with 5% in the SRT group. The grade 2+ GU toxicity rate was lower in the SRT arm (OR 0.34, 95% CI [0.17, 0.68], p=0.002) with no significant difference in grade 2+ GI toxicity rate (OR 0.48, 95% CI [0.047, 4.88], p=0.53). Similar FFBF rates were shown between ART and SRT, but we did not meet the protocol defined level set for non-inferiority. SRT spares approximately half of men from pelvic radiotherapy, and is associated with significantly lower levels of GU toxicity.

Interim PSA: Predicting for Biochemical Failure during Salvage Radiotherapy Following Prostatectomy

It is challenging to identify patients at higher risk of biochemical failure following salvage radiotherapy after having a radical prostatectomy. This work aims to determine if an interim PSA during radiotherapy would predict two year biochemical failure for patients who have salvage radiotherapy for a rising PSA following a radical prostatectomy for prostate cancer. A total of 185 patients in one center having salvage radiotherapy following a radical prostatectomy to a dose of 68Gy without androgen deprivation therapy between the years of 2010 and 2016 had their PSA recorded on the first day of radiotherapy, and again after completing the 25th fraction of 34 total fractions. Biochemical failure after radiotherapy was defined as a PSA value ≥0.2ng/mL within two years following radiotherapy. Univariate and multivariate Cox regression models were used for statistical analysis using statistical software. Factors investigated in univariate analysis other than a drop in PSA during radiotherapy included age, a Gleason score above 7, surgical margins status, the presence of extracapsular extension, PSA doubling time prior to radiotherapy, PSA at the time of radiotherapy, the presence of a detectable post-operative PSA immediately after surgery, whether or not a pelvic lymph node dissection was performed and whether or not there was seminal vesicle invasion. Factors with a p value <0.2 in univariate analysis were then used in a multivariate analysis. The two year freedom from biochemical failure was 60% (95% CI: 53% to 67%). Table 1 shows that on multivariate analysis, a drop in PSA during radiotherapy (p=0.003) and a positive surgical margin (p<0.0001) were significant factors for freedom from subsequent biochemical failure, while seminal vesicle invasion was associated with biochemical failure at two years (p=0.007). A PSA rise during salvage radiotherapy is predictive of biochemical failure at two years (HR 2.05). Factors such as seminal vesicle invasion and a negative surgical margin also predict for poor responders to salvage radiotherapy. If this is confirmed in further studies, then it may allow salvage radiotherapy to be abandoned at 50Gy into the treatment course, thereby potentially averting further futile radiotherapy and the risks of higher dose salvage treatment.Abstract 2619; Table 1Prognostic factors for biochemical failure at two years on multivariate analysis. *[Reference value]PSA During RadiotherapySurgical MarginsSeminal Vesicle InvasionGleason scoreSame or riseFallNegativePositiveYesNo>7≤7HR(95% Cl)2.050 (1.273-3.299)1*2.437 (1.493-3.978)1*2.044 (1.218-3.431)1*1.247 (0.731-2.127)1*P Value0.003<0.0010.0070.418 Open table in a new tab

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.

Performance characteristics of prostate-specific antigen density and biopsy primary Gleason score to predict biochemical failure in patients with intermediate prostate cancer who underwent radical prostatectomy.

BackgroundPrognosis for intermediate-risk prostate cancer (PCa) remains variable; therefore, we aimed to investigate high-risk factors for biochemical recurrence (BCR), and intermediate-risk PCa using radical prostatectomy to identify patients having equivalent BCR-free survival rates when compared to high-risk PCa.Patients and methodsA total of 441 medical records were analyzed, including those of 169 intermediate-risk and 272 high-risk PCa patients. Risk factors for time to BCR were tested and analyzed using Kaplan–Meier survival analysis, log-rank tests, and Cox proportion hazards models.ResultsIn the intermediate-risk group, prostate-specific antigen density (PSAD) and primary Gleason pattern were significant preoperative risk factors for BCR. Moreover, BCR-free survival of patients in the intermediate-risk group with a higher PSAD (>0.5 ng/mL/cm3) was comparable with that of patients in the high-risk group (P=0.735). When combining primary Gleason pattern 4 and 3 with PSAD cut-offs 0.3–0.7 ng/mL/cm3, we found that BCR-free survival of patients in the intermediate-risk group with a primary Gleason pattern 4 and PSAD >0.3 ng/mL/cm3 was comparable with that of patients in the high-risk group (P=0.463).ConclusionPSAD and primary Gleason pattern are potential risk factors associated with biochemical failure in intermediate-risk PCa patients after radical prostatectomy. Regarding significant differences in prognosis according to PSAD as well as primary Gleason pattern on biopsy, a subset of the intermediate-risk patients could be identified with outcomes that were equivalent to that of high-risk patients.

Subcutaneous Adipose Tissue Characteristics and Risk of Biochemical Recurrence in Men with High Risk Prostate Cancer

Obesity has become a worldwide epidemic. The interaction of obesity and excess adipose tissue on cancer biology continues to be an area of interest. The purpose of this study was to assess subcutaneous adipose tissue characteristics by computed tomography (CT) as potential imaging biomarkers in patients with high risk prostate cancer receiving radiation treatment (RT). This retrospective study included 185 men with high risk prostate cancer (PSA>20 ng/mL, Gleason score ≥ 8, or clinical extraprostatic extension) treated between 2001 and 2012. All patients received definitive, dose-escalated external beam RT along with a course of neoadjuvant, concurrent, and adjuvant androgen deprivation therapy (ADT). Each patient also had a treatment planning CT that included the L4-L5 vertebral interface and prostate specific antigen (PSA) measurements for at least 1 year following RT. The subcutaneous adipose tissue was contoured on a single axial CT slice at the level of L4-L5. The average CT attenuation, in Hounsfield units (HU), of the structure was calculated and defined as SATHU. SATAREA was defined as the cross-sectional area of the structure (in cm2) that was then normalized by the square of patient height. Biochemical failure (BF) was defined as a PSA rise of 2 ng/mL from the nadir. Freedom from BF (FFBF) was calculated from start time of ADT using the Kaplan-Meier method. Estimates of FFBF were stratified by SATHU and SATAREA quartiles. Median follow-up was 5.3 years. The mean SATHU (± standard deviation) was -99.2 HU (±6.3 HU) and the mean SATAREA was 94.7 cm2/m2 (±42.3 cm2/m2). No significant differences of SATHU and SATAREA were observed among different races or age groups. The 5 and 8-year rates of FFBF across all patients were 82.1% and 74%, respectively. Patients in the lowest quartile of SATHU experienced significantly higher FFBF compared to the other quartiles (Q4 vs. Q1, p=0.029; Q4 vs. Q2, p=0.045; Q4 vs. Q3, p=0.045). No other differences in FFBF were observed between quartiles of SATAREA or other quartiles of SATHU. Using CT imaging as a novel prognostic biomarker, low attenuation of abdominal adipose tissue was associated with a lower rate of biochemical failure in patients with high risk prostate cancer. Further research is needed to elucidate the biological underpinnings of this clinical finding and the role adipose tissue plays in modulating oncologic behavior and outcomes.

Does prostate volume has an impact on biochemical failure in patients with localized prostate cancer treated with HDR boost?

PurposeTo compare biochemical failure free survival (BFFS) of patients with small and large prostate glands treated with external beam radiation therapy (EBRT) and HDR (high dose rate) brachytherapy boost. Materials and methodsBetween 2002 and 2012, 548 patients were treated with EBRT followed by HDR boost. The effect of covariates and prostate volume on biochemical failure was analyzed by survival analysis and Cox regression model. ResultsThe median follow-up and age were not different between the two groups. The mean prostate gland volume at the time of CT planning was 48.1 and 76.0cc in small (<60cc) and large (⩾ 60cc) prostate volume, respectively (p<0.001). When PSA bounces were excluded, there was no significant difference between the two groups with a 5-years BFFS of 95.8% vs 92.3%, p=0.094. There were no significant differences between the two groups for urinary symptoms (IPSS) as well as acute and late GI toxicities. ConclusionsThis study showed that a HDR brachytherapy boost in large prostate gland cases is feasible at the price of increased PSA bounces. When the benign bounces are excluded, there is no significant difference between the two groups for tumor control and toxicity. Therefore, in our experience, there is no rational precluding the use of HDR boost in patients with a prostate size of 60 cc or more so long as an adequate dosimetry is achievable.

Limited improvement of incorporating primary circulating prostate cells with the CAPRA score to predict biochemical failure-free outcome of radical prostatectomy for prostate cancer

ObjectiveTo establish a prediction model for early biochemical failure based on the Cancer of the Prostate Risk Assessment (CAPRA) score, the presence or absence of primary circulating prostate cells (CPC) and the number of primary CPC (nCPC)/8ml blood sample is detected before surgery. Patients and methodsA prospective single-center study of men who underwent radical prostatectomy as monotherapy for prostate cancer. Clinical-pathological findings were used to calculate the CAPRA score. Before surgery blood was taken for CPC detection, mononuclear cells were obtained using differential gel centrifugation, and CPCs identified using immunocytochemistry. A CPC was defined as a cell expressing prostate-specific antigen and P504S, and the presence or absence of CPCs and the number of cells detected/8ml blood sample was registered. Patients were followed up for up to 5 years; biochemical failure was defined as a prostate-specific antigen>0.2ng/ml. The validity of the CAPRA score was calibrated using partial validation, and the fractional polynomial Cox proportional hazard regression was used to build 3 models, which underwent a decision analysis curve to determine the predictive value of the 3 models with respect to biochemical failure. ResultsA total of 267 men participated, mean age 65.80 years, and after 5 years of follow-up the biochemical-free survival was 67.42%. The model using CAPRA score showed a hazards ratio (HR) of 5.76 between low and high-risk groups, that of CPC with a HR of 26.84 between positive and negative groups, and the combined model showed a HR of 4.16 for CAPRA score and 19.93 for CPC. Using the continuous variable nCPC, there was no improvement in the predictive value of the model compared with the model using a positive-negative result of CPC detection. The combined CAPRA-nCPC model showed an improvement of the predictive performance for biochemical failure using the Harrell׳s C concordance test and a net benefit on DCA in comparison with either model used separately. The use of primary CPC as a predictive factor based on their presence or absence did not predict aggressive disease or biochemical failure. ConclusionAlthough the use of a combined CAPRA-nCPC model improves the prediction of biochemical failure in patients undergoing radical prostatectomy for prostate cancer, this is minimal. The use of the presence or absence of primary CPCs alone did not predict aggressive disease or biochemical failure.

Does Large Prostate Volume Has an Impact on Biochemical Failure in Patients With Localized Prostate Cancer Treated With HDR Boost?

Does Large Prostate Volume Has an Impact on Biochemical Failure in Patients With Localized Prostate Cancer Treated With HDR Boost?

Kinetics differences between PSA bounce and biochemical failure in patients treated with 125I prostate brachytherapy.

To determine the helpful factors to distinguish prostate-specific antigen failure from prostate-specific antigen bounce with large magnitude. From October 2004 to December 2009, 242 patients with prostate cancer treated with (125)I brachytherapy were analyzed, 88 patients were excluded because the follow-up durations were shorter than 5 years. Their median follow-up was 80.4 months (60.0-123.9). Prostate-specific antigen failure was determined using the Phoenix definition. Prostate-specific antigen bounce was defined as an increase ≥0.2 ng/ml above the nadir, followed by a spontaneous return to the nadir. Prostate-specific antigen bounce +2 was defined as a prostate-specific antigen rise by 2.0 ng/ml or more above the nadir. The 5-year biochemical relapse-free survival rate was 90.2%. Prostate-specific antigen failure and prostate-specific antigen bounce +2 were seen in 23 patients (14.9%) and 12 patients (7.8%), respectively. On univariate analysis, age at implant (P = 0.028), T stage (P = 0.020), time to prostate-specific antigen failure or prostate-specific antigen bounce (time to onset) (P = 0.0008), prostate-specific antigen velocity (P = 0.0003) and prostate-specific antigen doubling time (P = 0.0004) were significant for the distinction between prostate-specific antigen failure and prostate-specific antigen bounce +2. On multivariate analysis, no factor was the statistically significant factor. On receiver operating characteristic curve analysis, time to onset with a cutoff value of 29.8 months, prostate-specific antigen velocity of 0.18 ng/ml/month and prostate-specific antigen doubling time of 6.3 months had the highest accuracy of 82.9, 82.9 and 82.9% for prostate-specific antigen failure, respectively. Time to onset, prostate-specific antigen velocity and prostate-specific antigen doubling time would be helpful for distinction between prostate-specific antigen failure and prostate-specific antigen bounce +2.

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.

PD14-02 PERCENTAGE OF CANCER INVOLVEMENT IN POSITIVE CORES CAN PREDICT UNFAVOURABLE DISEASE IN MEN WITH LOW-RISK PROSTATE CANCER BUT ELIGIBLE FOR THE PROSTATE CANCER INTERNATIONAL: ACTIVE SURVEILLANCE CRITERIA

You have accessJournal of UrologyProstate Cancer: Localized II1 Apr 2014PD14-02 PERCENTAGE OF CANCER INVOLVEMENT IN POSITIVE CORES CAN PREDICT UNFAVOURABLE DISEASE IN MEN WITH LOW-RISK PROSTATE CANCER BUT ELIGIBLE FOR THE PROSTATE CANCER INTERNATIONAL: ACTIVE SURVEILLANCE CRITERIA Giorgio Ivan Russo, Sebastiano Cimino, Vincenzo Favilla, Eugenia Fragalà, Tommaso Castelli, Daniele Urzì, Massimo Madonia, and Giuseppe Morgia Giorgio Ivan RussoGiorgio Ivan Russo More articles by this author , Sebastiano CiminoSebastiano Cimino More articles by this author , Vincenzo FavillaVincenzo Favilla More articles by this author , Eugenia FragalàEugenia Fragalà More articles by this author , Tommaso CastelliTommaso Castelli More articles by this author , Daniele UrzìDaniele Urzì More articles by this author , Massimo MadoniaMassimo Madonia More articles by this author , and Giuseppe MorgiaGiuseppe Morgia More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1279AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Active surveillance has reached an important popularity with the intention to avoid or postpone surgery in patients with prostate cancer at low risk. Unfortunately, some doubts persist about the ability of the different criteria to predict an organ-confined prostate cancer. The aim of this study was to identify predictive factors of unfavourable disease and of biochemical failure in patients treated with radical prostatectomy (RP) but eligible for AS according to PRIAS criteria. We aimed to introduce and validate the percentage of cancer involvement in positive cores (CIPC) as potential worse predictive factor. METHODS From January 2002 to December 2007, 750 consecutive subjects underwent RP at a single institution. We identified 147 (19.05%) patients who were eligible for AS based on PRIAS criteria: clinical stage T1c or T2 disease, PSA level of ≤10 ng/ml, Gleason score ≤6, PSA-D of <0.2 ng/ml2 and fewer than three positive biopsy cores. We incorporated a new detailed histological parameter, the percentage of cancer involvement in positive cores (CIPC), calculated by dividing the cumulative cancer length (CCL) to the cumulative length of positive cores (CLPC). CCL was defined as the sum of the length of all cancerous lesions in mm while CLPC as sum of the length of all positive cores in mm. Unfavourable disease was considered as non-organ confined disease (pathological stage >pT2) and/or upgraded disease (Gleason score >6). RESULTS Of the 147 patients, 95 (66.43%) patients had favourable while 48 (33.57%) had unfavourable disease. In multivariate logistic regression, maximum cancer length (OR 12.52, p<0.01) and CIPC (OR 1.70, p<0.01) represented independent predictors of unfavourable PCa. The AUC analysis revealed significantly higher performance after including CIPC to the PRIAS criteria (0.61 vs. 0.94, p<0.01). A cutoff of 0.4 mm of CIPC was set to predict unfavourable disease with 93% specificity, 76% sensibility and 87% accuracy based on the ROC curve analysis. Finally, the 3- and 5-years BFS were significantly lower in subjects with CIPC ≥0.4 mm, 88.4 % and 81.0% vs. 97.8% and 95.7% respectively (p<0.01). CONCLUSIONS We showed that including CIPC to the pathological parameters of prostate biopsy is possible to estimate the presence of organ-confined disease in 93% of cases. Our findings suggest that the inclusion of CIPC to the prostate biopsy features could be helpful to avoid misclassification in patients eligible for AS according to the PRIAS criteria. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e411 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Giorgio Ivan Russo More articles by this author Sebastiano Cimino More articles by this author Vincenzo Favilla More articles by this author Eugenia Fragalà More articles by this author Tommaso Castelli More articles by this author Daniele Urzì More articles by this author Massimo Madonia More articles by this author Giuseppe Morgia More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP53-20 THE PREDICTIVE VALUE OF 2-YEAR POST-TREATMENT BIOPSY AFTER PROSTATE CANCER CONFORMAL RADIOTHERAPY FOR FUTURE OVERALL SURVIVAL AND BIOCHEMICAL FAILURE. THE RESULTS OF THE UK MRC RT01 TRIAL.

You have accessJournal of UrologyProstate Cancer: Detection & Screening II1 Apr 2014MP53-20 THE PREDICTIVE VALUE OF 2-YEAR POST-TREATMENT BIOPSY AFTER PROSTATE CANCER CONFORMAL RADIOTHERAPY FOR FUTURE OVERALL SURVIVAL AND BIOCHEMICAL FAILURE. THE RESULTS OF THE UK MRC RT01 TRIAL. Antoine Kass-iliyya, Gordana Jovic, Matthew Sydes, Cyril Fisher, Claire Murphy, David Nicol, and David Dearnaley Antoine Kass-iliyyaAntoine Kass-iliyya More articles by this author , Gordana JovicGordana Jovic More articles by this author , Matthew SydesMatthew Sydes More articles by this author , Cyril FisherCyril Fisher More articles by this author , Claire MurphyClaire Murphy More articles by this author , David NicolDavid Nicol More articles by this author , and David DearnaleyDavid Dearnaley More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1651AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives There is still an uncertainty regarding the significance of prostate biopsy status performed at 2 years after conformal radiotherapy (CFRT) used for treatment of localized prostate cancer. The objective of this analysis is to determine whether prostate biopsy status at around 2 years is predictive of overall survival (OS) and long-term biochemical progression free survival (bPFS). Methods Between January 1998 and December 2001, 843 consenting men with localized prostate cancer were randomized in to the MRC RT01 trial to receive either Control-64Gy or Escalated-74Gy of CFRT. Patients were stratified according to the risk of seminal vesicles (SV) involvement. As part of the trial’s protocol, post-CFRT prostate biopsies were requested at two years from the start of RT. Exclusion criteria for this analysis included biopsies performed before 18 months or after 36 months of starting radiotherapy and any evidence of biochemical failure or progression before or on the date of the biopsy. Analyses were performed using standard survival analysis methods with a landmark approach; hazard ratios (HR) are presented. Results 223 patient biopsies were taken and reviewed by a central pathologist. 46 of these patients met the exclusion criteria, leaving 177 patients for the main analysis. Baseline and patients characteristics were comparable in both groups. Median follow up was 7.8 years. In total, 64 bPFS events occurred: 46/145 in patients with negative biopsies, 6/18 in suspicious and 12/14 in positive. p: <0.001. HR: 4.69 (95%CI 2.44-9.01). Figure (1) Four deaths secondary to prostate cancer occurred: 1 (0.7%) in patient with negative biopsy and 3 (21.4%) in patients with positive biopsies. Twenty-seven deaths from any cause occurred: 21/145 (14%) in patients with negative biopsies, 2/18 (11%) in suspicious and 4/14 (29%) in positive. p: 0.410. HR: 1.58 (95%CI 0.53-4.71). Conclusions The risk of biochemical failure in patients with positive biopsies at 2 years is almost five times higher than in patients with negative or suspicious biopsies and the risk of death from any cause is about 1.6 times higher. Post-treatment prostate biopsies are a strong predictor of future biochemical failure. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e596-e597 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Antoine Kass-iliyya More articles by this author Gordana Jovic More articles by this author Matthew Sydes More articles by this author Cyril Fisher More articles by this author Claire Murphy More articles by this author David Nicol More articles by this author David Dearnaley More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Elevated hyaluronan and hyaluronan‐mediated motility receptor are associated with biochemical failure in patients with intermediate‐grade prostate tumors

The clinical course of prostate cancer (PCa) measured by biochemical failure (BF) after prostatectomy remains unpredictable in many patients, particularly in intermediate Gleason score (GS) 7 tumors, suggesting that identification of molecular mechanisms associated with aggressive PCa biology may be exploited for improved prognostication or therapy. Hyaluronan (HA) is a high molecular weight polyanionic carbohydrate produced by synthases (HAS1 through HAS3) and fragmented by oxidative/nitrosative stress and hyaluronidases (HYAL1 through HYAL4, SPAM1) common in PCa microenvironments. HA and HA fragments interact with receptors CD44 and hyaluronan-mediated motility receptor (HMMR), resulting in increased tumor aggressiveness in experimental PCa models. This study evaluated the association of HA-related molecules with BF after prostatectomy in GS7 tumors. Tissue microarrays were constructed from a 96-patient cohort. HA histochemistry and HAS2, HYAL1, CD44, CD44v6, and HMMR immunohistochemistry were quantified using digital pathology techniques. HA in tumor-associated stroma and HMMR in malignant epithelium were significantly and marginally significantly associated with time to BF in univariate analysis, respectively. After adjusting for clinicopathologic features, both HA in tumor-associated stroma and HMMR in malignant epithelium were significantly associated with time to BF. Although not significantly associated with BF, HAS2 and HYAL1 positively correlated with HMMR in malignant epithelium. Cell culture assays demonstrated that HMMR bound native and fragmented HA, promoted HA uptake, and was required for a promigratory response to fragmented HA. HA and HMMR are factors associated with time to BF in GS7 tumors, suggesting that increased HA synthesis and fragmentation within the tumor microenvironment stimulates aggressive PCa behavior through HA-HMMR signaling.