Postoperative Postoperative Prostate-specific Antigen Research Articles

Prognosis based on postoperative PSA levels and treatment in prostate cancer with lymph node involvement.

The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies. Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS). In the persistent PSA group (PSA ≥ 0.1ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone. This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI.

Treatment outcomes of our patients with prostate cancer who underwent postoperative radiotherapy

Aims: Prostate cancer is one of the most common cancers in men. Surgery, radiotherapy or active surveillance are the treatment options. Treatment is decided according to risk group of the patient. Postoperative radiotherapy is delivered in selected patients to increase the local control rates. The aim of this study is to report the treatment results of patients who received postoperative radiotherapy for localized prostate cancer. Methods: This retrosepctive study included 78 prostate cancer patients who received postoperative radiotherapy between 2011 and 2023. All patients except who had pathologically positive lymph nodes were included into the study. Overall survival, progression free survival, and associated pathological parameters were evaluated by using IBM SPSS programme version 20. Results: The mean follow-up time was 66.7 (IQR 25-75:41,6-89,6) months. Five and 10-year overall survival rates were 93%, and 67.3% respectively; (median (95% CI); NR (not reach): while 5 and 10-year progression-free survival rates were 90.3%, and 50.4, respectively; (median (95% CI); 135.3± (105.9-165.7). Postoperative prostate specific antigen (PSA) and pre-RT PSA values, and the effects of these parameters on progression-free survival was analyzed, median progression-free survival was higher in patients with postoperative PSA values ? 0.185 (135.6±24.4 vs 113.3±6.4, p:0.001). Five and 10 year overall survival and progression-free survival rates of patients with a high gleason score who underwent postoperative radiotherapy was observed lower than the others (86.9% and 46.3%, p=0.006; 86.9% and 33.8%, p=0.009 respectively). Conclusion: Postoperative radiotherapy is generated best results in progression free survival and overall survival in patients with low pre-rt psa and high gleason score prostate cancer cases

Salvage Versus Adjuvant Radiation Therapy Following Radical Prostatectomy in Localised Prostate Cancer: A War Without a Winner

ObjectiveTo review current literature regarding the efficacy of adjuvant radiation therapy (ART) and salvage radiation therapy (SRT) following radical prostatectomy (RP) in patients with undetectable postoperative prostate-specific antigen (PSA) levels and high-risk features of prostate cancer (PCa) recurrence.MethodsSeven randomized controlled trials focused on the use of ART compared with either observation or SRT after RP that had been published in PubMed up to May 2022 were reviewed.ResultsThe use of ART following RP has been the treatment of choice over the past decade. Three RCTs comparing ART with early SRT show that SRT given as soon as biochemical recurrence (BCR) is detected is not inferior to ART while it offers the opportunity to avoid overtreatment and potential RT-related side effects. A meta-analysis summarizing the results from these trials supports these findings.ConclusionsEarly SRT may be suggested as the standard of care for patients with PCa and high-risk features for disease recurrence following RP. Nevertheless, further investigations are needed to identify those patients who will benefit from ART, particularly, in case of lymph node involvement. Moreover, some patients might avoid SRT despite reaching detectable postoperative serum PSA levels.

Novel nomogram to predict biochemical recurrence-free survival after radical prostatectomy.

Conditional survival represents the probability of subsequent survival given that patients have already survived a certain length of time. Several models predict biochemical recurrence (BCR) after radical prostatectomy. However, none of them include postoperative prostate-specific antigen (PSA). We aimed to analyze BCR-free survival evolution over time and develop a nomogram incorporating the postoperative PSA value to predict BCR-free survival. We included patients treated with robot-assisted radical prostatectomy (RARP) for prostate cancer between 2009 and 2021 and calculated conditional survival. Cox proportional hazard regression analysis was used to assess the predictive variables of BCR. We developed a nomogram predicting BCR-free survival three and five years after RARP. We used c-index and decision curve analyses to compare the nomogram with the Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score. We included 718 patients. The overall 3- and 5-year BCR-free survival rates were 85.1% and 75.7%, respectively. The 5-year BCR-free survival rates increased to 78.9%, 82.9%, 85.2%, and 84.7% for patients surviving 1, 2, 3, and 4years without BCR, respectively. We developed a nomogram including the pathological Gleason score and T stage, positive surgical margin, PSA ≥ 0.05ng/mL at one year, and lymph node involvement to predict BCR at 3 and 5years postoperatively. Our nomogram presented a higher c-index (0.89) than the CAPRA-S score (0.78; p = 0.001) and a positive net benefit at 3 and 5years postoperatively in the decision curve analyses. The 5-year conditional BCR-free survival increased with survival without BCR. The developed nomogram significantly improved the accuracy in predicting BCR-free survival after RARP.

Utilizing Preoperative Magnetic Resonance Imaging to Self-assess Enucleation Ratio in Holmium Laser Enucleation of the Prostate

ObjectiveTo determine if transition zone (TZ) volume as measured by magnetic resonance imaging (MRI) correlates closely with specimen weight and postoperative prostate-specific antigen (PSA) and to determine if this correlation improved with increased experience. We hypothesize that information from a preoperative MRI can be leveraged to self-assess competency in holmium laser enucleation of the prostate (HoLEP). MethodsFrom August 2018 to June 2021 567 men were identified who underwent HoLEP by a single surgeon and had their data entered into a database. Ninety-seven men were identified who had an MRI in our image archives. A radiologist blinded to the specimen weight measured the transition zone (TZ) using image analysis software. TZ volume was then correlated with specimen weight for the entire study period and subdivided into four consecutive periods. Preoperative and Postoperative PSA data was analyzed. ResultsSeventeen percent of men who underwent HoLEP at our institution had an MRI preoperatively. The TZ to total prostate volume ratio was 70%. The overall correlation coefficient between TZ volume and specimen weight was 0.914 (P-value <.001). There was no statistically significant improvement in correlation coefficient over time when divided into four equal subgroups. Median PSA reduction was 91% (7.9-0.7 ng/dL). ConclusionPreoperative MRI derived TZ volume correlates closely with specimen weight. We present a reference cohort from a high volume HoLEP center to facilitate HoLEP learners to self-assess competency. Lack of increased correlation over time is likely due to an experienced HoLEP surgeon who is on the flatter portion of his learning curve.

Integrating Prostate-specific Antigen Kinetics into Contemporary Predictive Nomograms of Salvage Radiotherapy After Radical Prostatectomy

BackgroundSalvage radiotherapy (SRT) is an established treatment for men with biochemical recurrence following radical prostatectomy (RP). There are several risk factors associated with adverse outcomes; however, the value of postoperative prostate-specific antigen (PSA) kinetics is less clear in the ultrasensitive PSA era. ObjectiveTo characterize the impact of PSA kinetics on outcomes following SRT and generate nomograms to aid in identifying patients with an increased risk of adverse clinical outcomes. Design, setting, and participantsA multi-institutional analysis was conducted of 1005 patients with prostate cancer treated with SRT after RP, with a median follow-up of 5 years. Outcome measurements and statistical analysisVariables examined include immediate postoperative PSA, postoperative PSA doubling time (DT), and pre-SRT PSA, in addition to previously identified predictive factors. Multivariable survival analyses were completed using Fine-Gray competing risk regression. Rates of biochemical failure (BF), distant metastasis (DM), and prostate cancer–specific mortality (PCSM) were estimated by the cumulative incidence method. Nomograms were generated from multivariable competing risk regression with bootstrap cross-validation. Results and limitationsFactors associated with BF after SRT include PSA DT <6 mo, initial postoperative PSA ≥0.2 ng/ml, higher pre-SRT PSA, lack of androgen deprivation therapy, a higher Gleason score (GS), negative margins, seminal vesicle invasion, lack of pelvic nodal radiation, radiation total dose <66 Gy, a longer RP to SRT interval, and older age (p < 0.05 for each). Factors associated with DM include PSA DT <6 mo, pre-SRT PSA, a higher GS, and negative margins. Factors associated with PCSM include PSA DT not calculable or <6 mo and a higher GS. Nomograms were generated to estimate the risks of BF (concordance index [CI] 0.74), DM (CI 0.77), and PCSM (CI 0.77). Limitations include retrospective nature, broad treatment eras, institutional variations, and multiple methods available for the estimation of PSA DT. ConclusionsPostoperative PSA kinetics, particularly pre-SRT PSA and PSA DT, are strongly associated with adverse oncologic outcomes following SRT and should be considered in management decisions. Patient summaryIn this report of men with prostate cancer who developed a prostate-specific antigen (PSA) recurrence after prostatectomy, we found that PSA levels after surgery and how quickly a PSA level doubles significantly impact the chance of prostate cancer recurrence after salvage radiation therapy. Based on this information, we created a tool to calculate a man’s chance of cancer recurrence after salvage radiation therapy, and these estimations can be used to discuss whether additional treatment with radiation should be considered.

Identification of a five gene signature to predict time to biochemical recurrence after radical prostatectomy.

Identification of novel biomarkers associated with high-risk prostate cancer or biochemical recurrence can drive improvement in detection, prognosis, and treatment. However, studies can be limited by small sample sizes and sparse clinical follow-up data. We utilized a large sample of prostate specimens to identify a predictive model of biochemical recurrence following radical prostatectomy and we validated this model in two external data sets. We analyzed prostate specimens from patients undergoing radical prostatectomy at Hartford Hospital between 2008 and 2011. RNA isolated from formalin-fixed paraffin-embedded prostates was hybridized to a custom Affymetrix microarray. Regularized (least absolute shrinkage and selection operator [Lasso]) Cox regression was performed with cross-validation to identify a model that incorporated gene expression and clinical factors to predict biochemical recurrence, defined as postoperative prostate-specific antigen (PSA) > 0.2 ng/ml or receipt of triggered salvage treatment. Model performance was assessed using time-dependent receiver operating curve (ROC) curves and survival plots. A total of 606 prostate specimens with gene expression and both pre- and postoperative PSA data were available for analysis. We identified a model that included Gleason grade and stage as well as five genes (CNRIP1, endoplasmic reticulum protein 44 [ERP44], metaxin-2[MTX2], Ras homolog family member U [RHOU], and OXR1). Using the Lasso method, we determined that the five gene model independently predicted biochemical recurrence better than a model that included Gleason grade and tumor stage alone. The time-dependent ROCAUC for the five gene signature including Gleason grade and tumor stage was 0.868 compared to an AUC of 0.767 when Gleason grade and tumor stage were included alone. Low and high-risk groups displayed significant differences in their recurrence-free survival curves. The predictive model was subsequently validated on two independent data sets identified through the Gene Expression Omnibus. The model included genes (RHOU, MTX2, and ERP44) that have previously been implicated in prostate cancer biology. Expression of a small number of genes is associated with an increased risk of biochemical recurrence independent of classical pathological hallmarks.

PD52-11 UNIQUE GENOMIC SIGNATURE TO PREDICT BIOCHEMICAL RECURRENCE FOLLOWING RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Markers II (PD52)1 Apr 2020PD52-11 UNIQUE GENOMIC SIGNATURE TO PREDICT BIOCHEMICAL RECURRENCE FOLLOWING RADICAL PROSTATECTOMY John Corradi, Christine Cumarasamy, Ilene Staff, Joseph Tortora, Andrew Salner, and Joseph Wagner* John CorradiJohn Corradi More articles by this author , Christine CumarasamyChristine Cumarasamy More articles by this author , Ilene StaffIlene Staff More articles by this author , Joseph TortoraJoseph Tortora More articles by this author , Andrew SalnerAndrew Salner More articles by this author , and Joseph Wagner*Joseph Wagner* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000954.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Identification of novel biomarkers associated with high risk prostate cancer or biochemical recurrence can drive improvement in detection, prognosis, and treatment. Using a large sample of prostate specimens, the objective was to identify gene expression signatures that would predict biochemical recurrence following radical prostatectomy. METHODS: Between 2008 and 2011, patients undergoing radical prostatectomy at Hartford Hospital were consented to submit specimens for whole genome gene expression as part of the Total Cancer Care Consortium. RNA isolated from formalin-fixed paraffin-embedded prostates was hybridized to a custom Affymetrix microarray. Regularized Least Absolute Shrinkage and Selection Operator(LASSO) Cox regression was performed with cross-validation to identify a gene expression signature that improves risk prediction. Recurrence was defined as post-operative prostate-specific antigen (PSA) >0.2 ng/mL or triggered salvage treatment. Model performance was assessed using time-dependent receiver operating characteristic (ROC) curves (with area under the curve, AUC) and survival plots. RESULTS: Pre- and post-operative PSA data were available for 606 prostate specimens. Using the LASSO model, a 5 gene signature was identified that independently predicted biochemical recurrence above Gleason grade and tumor stage. The time-dependent ROC AUC for the 5 gene signature with Gleason grade and tumor stage was 0.868 compared to an AUC of 0.767 for Gleason grade and tumor stage alone. The predictive model was subsequently validated on two independent gene expression data sets with AUC’s of 0.837 and 0.839. Patients stratified into low and high risk groups based on the predictive model score displayed significant differences in their recurrence-free survival curves. The model included genes (RHOU, MTX2, and ERP44) that have previously been implicated in prostate cancer biology. CONCLUSIONS: Our unique 5 gene signature panel can improve prediction of biochemical recurrence over the use of classical pathological hallmarks alone. Further validation should involve more specific sub-populations of prostate cancer patients, including those with earlier biochemical recurrence. Source of Funding: Unfunded. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1094-e1094 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Corradi More articles by this author Christine Cumarasamy More articles by this author Ilene Staff More articles by this author Joseph Tortora More articles by this author Andrew Salner More articles by this author Joseph Wagner* More articles by this author Expand All Advertisement PDF downloadLoading ...

Effect of Preoperative Dutasteride on Holmium Laser Enucleation of the Prostate

Purpose: The aim of this study was to compare and investigate the efficacy of using the 5α-reductase inhibitor dutasteride after holmium laser enucleation of the prostate (HoLEP) to improve postoperative urination and surgery-related complications. Methods: This is a retrospective observational study comparing patients who received or did not receive 5α-reductase inhibitors prior to HoLEP. Of a total of 270 patients, 40 received the 5α-reductase inhibitor dutasteride. We compared the factors including age, postoperative maximal flow rate (MFR; mL/s), postoperative prostate-specific antigen (PSA) (ng/mL), preoperative MFR (mL/s), preoperative PSA (ng/mL), prostate cancer (%), operative time (min), preoperative residual urine (mL), postoperative residual urine (mL), urinary incontinence (day 1; %), urinary incontinence (1 month; %), urinary incontinence (3 months; %), urethral catheter indwelling period (days), morcellation time (min), enucleation time (min), intraoperative complications (%), postoperative complications (%), prostate volume (mL), enucleated weight (g), and hospitalization period (days). Results: Postoperative PSA (p = 0.0071), morcellation time (p = 0.0444), postoperative complications (p = 0.0350) and prostate volume (p = 0.0069), but not enucleated prostate weight (p = 0.8809), were significantly lower in the dutasteride group. Importantly, enucleation efficiency and morcellation efficiency did not show any significant difference between the dutasteride and the non-dutasteride groups. Conclusions: Use of a preoperative 5α-reductase inhibitor significantly correlated with surgery-related factors, with less morcellation time, fewer postoperative complications, and lower postoperative PSA. Surgeons performing HoLEP may wish to take these findings into account.

Pathologically Node-Positive Prostate Carcinoma – Prevalence, Pattern of Care and Outcome From a Population-Based Study

AimsTo evaluate the prevalence, patterns of care and outcome of pathologically node-positive (pN+) prostate cancer (P-Ca) after radical prostatectomy from a provincial population database. Patients and methodsPatients were identified from a provincial cancer registry and a genitourinary cancer outcomes unit (2005–2014). Of a total of 4723 patients who underwent radical prostatectomy, 167 patients with pN+ P-Ca were identified (28/2181 from 2005–2007 and 139/2542 from 2010–2014). Persistently elevated postoperative prostate-specific antigen (PSA) ≥ 0.2 ng/ml was noted in 52 (31%) patients, 23 (44.2%) of whom had salvage androgen deprivation therapy plus radiotherapy (ADT + RT), 25 (48%) were managed with ADT alone and four (7.8%) had no treatment. Of 115 patients with postoperative PSA <0.2 ng/ml, 47 (41%) had ADT alone and 50 (43.5%) had ADT + RT. Survival estimation was carried out using the Kaplan–Meier method. The association of prognostic factors with survival was evaluated using univariate and multivariate analysis and was limited to the newer cohort (2010–2014). ResultsThe median age was 64 years; the median baseline PSA was 12.5 ng/mL (range 2.5–108.4). After a median follow-up of 48 months, overall survival at 5 and 10 years for the entire cohort were 89% and 81%, respectively, and distant metastasis-free survival (DMFS) at the same time points were 77% and 58%, respectively. For the newer cohort, 5-year overall survival and DMFS were 91.5% and 76%, respectively. On univariate analysis, persistently elevated postoperative PSA ≥0.2 ng/ml (P = 0.0003), seminal vesicle involvement (P = 0.027), ≥2 nodes (P = 0.035) and ADT alone (P = 0.054) had a poor prognostic impact on DMFS, whereas margin involvement had a marginally negative influence on overall survival (P = 0.06). On multivariate analysis, postoperative PSA ≥0.2 ng/ml (hazard ratio 4.4, 95% confidence interval 1.7–11.4; P = 0.002) continued to have a significant association with DMFS. On a sensitivity analysis, postoperative PSA ≥0.1 also had a significant association with DMFS on univariate and multivariate analysis (hazard ratio 3.69, 95% confidence interval 1.32–10.29; P = 0.01). Similarly, postoperative PSA ≥0.4 ng/ml had a significant association with DMFS (hazard ratio 3.87, 95% confidence interval 1.58–9.46, P = 0.003). ConclusionThis study showed a notable difference in the proportion of pN+ P-Ca patients between two different time cohorts. A significant association of persistently elevated postoperative PSA with DMFS was noted in our study. This must be accounted for while tailoring postoperative treatment in pN+ P-Ca.

Comparison of lymph node dissection and short-term efficacy of laparoscopic radical operation in patients with different grades of prostate cancer

Objective To investigate and compare pelvic lymph node dissection and the short-term efficacy of laparoscopic radical operation in patients with different Gleason grades of prostate cancer. Methods The medical records of 98 patients with prostate cancer treated by laparoscopic radical operation in our hospital were analyzed retrospectively. According to the preoperative Gleason score, the patients were divided into group A (Gleason score ≤ 6 points, 37 cases), group B (Gleason score of 3+ 4=7 points or 4+ 3=7 points, 42 cases) and group C (Gleason score≥ 8 points, 19 cases). The situation of operation, the incidence of postoperative complications, preoperative and postoperative prostate specific antigen (PSA) levels and the probability of postoperative PSA level > 0.2 ng/mL were compared among the 3 groups. All patients were followed up to August 2017, and the biochemical recurrence rates of two groups were recorded. Results There was no patient undergoing lymph node dissection in group A, 38 patients undergoing pelvic lymph node dissection in group B, and all patients undergoing pelvic lymph node dissection in group C. There was no significant difference between group B and group C in the number of dissected lymph nodes (P>0.05). The operation time and intraoperative blood loss of group A were shorter or less than those of group B or group C (P 0.05). The positive rates of incisal margin in group A and group B (0% and 2.38%) were lower than that in group C (15.79%) (P 0.05). PSA levels in the 3 groups at 1 month after operation were lower than those before operation (P 0.05). The odds of PAS level > 0.2 ng/mL in group A and group B (0 and 2.38%) were significantly lower than that in group C (15.79%) (P<0.05). The biochemical recurrence rates of group A and group B (2.70% and 7.14%) were lower than that of group C (26.32%) (P<0.013). Conclusions Lymph node dissection should be carried out after evaluating the risk of pelvic lymph node dissection in patients with prostate cancer before laparoscopic radical operation. The lower the Gleason score is, the lower the positive margin rate of incisal margin and biochemical recurrence rate are. Key words: Prostatic Neoplasms; Laparoscopy; Lymph Node Excision

First postoperative PSA is associated with outcomes in patients with node positive prostate cancer: Results from the SEARCH database

ObjectiveTo analyze factors associated with metastases, prostate cancer-specific mortality, and all-cause mortality in pN1 patients. Materials and methodsWe analyzed 3,642 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Pathologic Gleason grade, number of lymph nodes (LN) removed, and first postoperative prostate-specific antigen (PSA) (<0.2 ng/ml or ≥0.2 ng/ml) were among covariates assessed. Cox regression was used to analyze the association between characteristics and survival outcomes. Kaplan-Meier was used to estimate survival in pN1 patients stratified by first postoperative PSA. ResultsOf 3,642 patients, 124 (3.4%) had pN1. There were 71 (60%) patients with 1 positive LN, 32 (27%) with 2 positive LNs, and 15 (13%) with ≥3. Among men with pN1, first postoperative PSA was<0.2ng/ml in 46 patients (51%) and ≥0.2ng/ml in 44 patients (49%). Univariable Cox regression determined pathological Gleason grade (P = 0.021), seminal vesicle invasion (P = 0.010), and first postoperative PSA ≥0.2 ng/ml (P = 0.005) were associated with metastases. First postoperative PSA ≥0.2ng/ml was associated with metastasis on multivariable analysis (P = 0.046). Log-rank analysis revealed a more favorable metastases-free survival in patients with a first postoperative PSA<0.2ng/ml (P = 0.001). Estimated 5-year metastases-free survival rate was 99% for patients with a first postoperative PSA<0.2ng/ml and 87% for ≥0.2ng/ml. ConclusionspN1 patients with a first postoperative PSA ≥0.2ng/ml were more likely to develop metastases. First postoperative PSA may be useful in identifying pN1 patients who harbor distant disease and aid in secondary treatment decisions.

Novel Clinical Tools to Guide Management of Prostate Cancer: Preoperative Predictive Models to Identify Patients at Risk for Needing Adjuvant Radiation (T3 or +margin) or Having Detectable Postoperative PSA

Several valuable models use preoperative data to predict organ- confined disease at the time of radical prostatectomy. However, there are no similar tools to predict which patients will qualify for adjuvant radiation therapy (ART), or have a detectable postoperative prostate specific antigen (PSA). We developed logistic regression models to predict risk for extracapsular extension (ECE) and seminal vesicle invasion (SVI) and compared them to others (Roach, CAPRA, Memorial Sloan Kettering, and Partin models). We then created two novel formulas to predict risk for ART (either T3 or +margin) or detectable postoperative PSA. We conducted a retrospective multi-institutional review of patients with clinically localized prostate adenocarcinoma who had radical prostatectomy from 2001-2015 (N=1,676) at Kaiser Permanente in Southern California. Patients treated with preoperative leuprolide or missing data were excluded. Three multivariate models were developed to predict ECE, SVI, and either ECE or SVI. A fourth model was developed to predict ECE/SVI/+margin. A fifth model was developed to predict detectable postoperative PSA (≥0.1). The area under the receiver curve (AUC) was calculated and corrected using bootstrap resampling with 2000 samples. Statistical analysis was performed with R version 3.3.1. Statistically significant factors on multivariate analysis included percent positive biopsy cores, biopsy Gleason score, PSA, and clinical T-stage. Age and year of surgery were not statistically significant. The ECE, SVI, and ECE/SVI models (AUC 0.69-0.81) performed favorably compared to other tools (AUC 0.72-0.79) [Table 1]. Our T3/+margin model performs at corrected AUC 0.75. Our detectable postoperative PSA model performs at corrected AUC 0.81 [Table 1]. We developed three models predicting risk of extraprostatic disease, which compared favorably over other widely used models. We created two novel clinical formulas to predict preoperatively whether patients may require ART or have a detectable postoperative PSA. These tools may help guide the selection of surgery or radiation upfront, and could potentially reduce dual modality treatment. While our novel clinical prediction models performed well in our data set, no known tools exist for comparison, and external validation is needed.Abstract 2630; Table 1RoachCAPRAMSKPartinKaiserECE (25% risk) AUC0.740.740.760.720.69 Sen/Spec1.00/00.63/0.701.00/00.87/0.460.37/0.91 PPV/NPV0.22/ NA0.39/0.860.22/0.830.31/0.920.54/0.84SVI (25% risk) AUC0.760.780.790.760.81 Sen/Spec0.47/0.850.22/0.960.28/0.960.03/0.990.39/0.94 PPV/NPV0.27/0.930.39/0.910.47/0.920.40/0.900.42/0.93ECE/SVI (40% risk) AUC---0.760.79 Sen/Spec---0.64/0.720.52/0.86 PPV/NPV---0.48/0.830.61/0.82ECE, SVI, or +margin (20% risk) AUC----0.75 Sen/Spec----0.91/0.35 PPV/NPV----0.44/0.87Detectable 1st Postop PSA (20% risk) AUC----0.81 Sen/Spec----0.36/0.95 PPV/NPV----0.34/0.96 Open table in a new tab

Correlation between postoperative prostate-specific antigen and biochemical recurrence in positive surgical margin patients: Single surgeon series.

BackgroundTo evaluate the relationship between postoperative prostate-specific antigen (PSA) levels and biochemical recurrence (BCR) after radical prostatectomy, especially in patients with positive surgical margins (PSMs).Materials and methodsA total of 144 patients who underwent radical prostatectomies performed by a single surgeon without any neoadjuvant or adjuvant treatment were analyzed. Differences in clinicopathological factors were compared by surgical margin status, and the relationship between postoperative PSA level and BCR in patients with PSMs was evaluated.ResultsFifty of the 144 patients (34.7%) had PSMs. Of these, 74% experienced BCR. The negative surgical margins and PSMs groups differed significantly in terms of PSA level at diagnosis, clinical T stage, and risk group by the cancer of the prostate risk assessment score (P = 0.002, P = 0.002, and P = 0.004, respectively). Also, the nadir PSA level, tumor volume, and BCR rate differed between the two groups (P = 0.007, P = 0.015, and P = 0.005, respectively) On Kaplan–Meier analysis, BCR-free survival was better in the negative surgical margins than the PSMs group (64.1 vs. 55.4 months, log-rank test, P = 0.011). BCR-free survival did not differ significantly in PSMs patients according to whether PSA level was or was not detectable at 1 month postoperatively. However, BCR-free survival improved when the nadir PSA level was undetectable (compared to detectable) in PSMs patients (64.3 vs. 26.1 months, log-rank test, P < 0.001). In PSMs patients belonging to the high risk group by cancer of the prostate risk assessment score, BCR-free survival was significantly better when the PSA level attained the nadir within 3 months, compared to > 6 months, postoperatively (64.2 vs. 29.5 months, log-rank test, P = 0.022).ConclusionIf PSA is detectable in PSMs patients until 1 month after operation, cautious observation may be possible. If the nadir is attained within 3 months postoperatively in high-risk patients with PSMs, better BCR-free survival may be expected.

Positive surgical margins after radical prostatectomy: What should we care about?

Positive surgical margins (PSMs) after radical prostatectomy (RP) are a known factor associated with biochemical recurrence (BCR) and raise the issue of adjuvant treatment by radiotherapy versus salvage treatment at recurrence. To help this choice, our study aimed to analyze BCR-free survival and factors associated with BCR in patients with PSM and undetectable postoperative prostate-specific antigen (PSA). Between 2005 and 2008, 630 patients had RP for localized prostate cancer in our center. We included patients with PSM, uninvaded nods, undetectable postoperative PSA and no adjuvant treatment. The 5-year BCR-free survival was calculated using Kaplan-Meier method. Logistic regression models were used to determine the factors associated with BCR in univariate and multivariate analyses (Cox model). The PSM rate was 32.7 % (n = 206 patients), and 110 patients corresponded to the inclusion criteria. The median follow-up was 72 months. The BCR rate was 30 % with a 5-year BCR-free survival of 83.9 %. The factors significantly associated with BCR were preoperative PSA, predominance and percentage of Gleason 4, tumor volume, PSM length and predominance of Gleason 4 at the margin. In the multivariate analysis, the remaining two significant factors were PSM length [OR 4.35, 95 % CI (1.011-1.421), p = 0.037] and tumor volume [OR 4.29, 95 % CI (1.011-1.483), p = 0.038]. Over a 5-year follow-up, only one-third of patients experienced BCR. It might be reasonable to postpone adjuvant radiotherapy for patients with PSM and undetectable PSA after RP. Tumor volume and PSM length were associated with BCR and should be taken into account in the postoperative treatment management.

The use of early postoperative prostate-specific antigen to stratify risk in patients with positive surgical margins after radical prostatectomy.

BackgroundIt is well recognized that the presence of positive surgical margins (PSM) after radical prostatectomy (RP) adversely affects cancer specific outcomes and recent evidence from randomized trials supports the use of adjuvant radiotherapy in these cases. However, not all of the patients with PSM develop disease recurrence and the policy of adjuvant radiation could result in considerable over-treatment. We investigated the ability of early postoperative prostate specific antigen (PSA) and PSA decline rates to stratify the risk of disease progression during the first weeks after the surgery thereby allowing adequate time for planning eventual adjuvant therapy.MethodsWe studied 116 consecutive patients with the finding of PSM after RP for localized prostate cancer between 2001 and 2012. No patients were treated with radiation or hormonal therapy. An intensive postoperative PSA monitoring using ultrasensitive assay started first at day 14 after the surgery, then at day 30, 60, 90 and 180, and subsequently in 3 monthly intervals. Biochemical recurrence (BCR) presented the failure of surgical treatment and it was defined as PSA ≥0.2 ng/ml. The ability of PSA decline parameters to predict BCR was assessed using Cox regression model and area under the curve (AUC) calculation.ResultsOverall 55 (47%) patients experienced BCR during median follow-up of 31.4 months (range 6–69). Preoperative PSA, pathologic Gleason sum and pathologic grade failed to reveal any association with observation of BCR. Postoperative PSA levels achieved significant predictive accuracy already on day 30 (AUC 0.74). PSA >0.073 ng/ml at day 30 increased significantly the risk of BCR (HR 4.35, p < 0.001). Predictive accuracy was significantly exceeded on day 60 (AUC 0.84; p < 0.001), while further enhancements on day 90 (AUC 0.84) and 180 (AUC 0.91) were not significant.ConclusionsThe level of ultrasensitive PSA yields valuable information about the prostatectomy outcome already at the first month after the surgery and should aid risk stratification in patients with PSM. Patients not likely to experience subsequent disease progression may be spared the toxicity of immediate adjuvant radiotherapy.

The PROCAINA (PROstate CAncer INdication Attitudes) Project (Part I): a survey among Italian radiation oncologists on postoperative radiotherapy in prostate cancer

Radiotherapy (RT) has an established role in the postoperative treatment of prostate cancer patients with extracapsular extension, positive surgical margins or a detectable post-operative prostate-specific antigen (PSA). Despite the large number of patients treated with postoperative RT, some issues about optimal technique, doses, volumes, timing and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of postoperative prostate cancer patients. During the 2010 National Congress of the Italian Association of Radiation Oncology (AIRO), four clinical cases were presented to the attending radiation oncologists. Two of them were cases of postoperative prostate cancer, differing in T stage of the primary tumour according to the TNM classification, preoperative staging procedures, preoperative PSA (iPSA), Gleason score of biopsies and definitive pathological specimen after surgery and postoperative PSA. For each clinical case, the radiation oncologists were asked to: (a) give indication to new pre-treatment procedures for staging; b) give indication to postoperative treatment; (c) to define specifically, where indicated, the total dose, type of fractionation, treatment volumes, type of technique, type of image-guided setup control; (d) indicate whether adjuvant hormonal therapy should be prescribed; (e) define criteria that mostly influenced the prescription. A descriptive statistical analysis was then performed. A total of 300 questionnaires were distributed amongst radiation oncologists attending the congress; 128 were completed and considered for this analysis (41%). Some important differences were shown in prescribing and performing postoperative radiotherapy, and some significant differences with international guidelines and data available from the literature were also reviewed and discussed. Despite the results of clinical trials, significant differences still exist among Italian radiation oncologists in deciding postoperative treatment in prostate cancer patients. These patients probably deserve a more uniform approach based on updated, detailed and evidence-based recommendations.

Identifying Node-Positive Prostate Cancer Patients Who May Benefit From Adjuvant Pelvic Radiation Following Prostatectomy

Identifying Node-Positive Prostate Cancer Patients Who May Benefit From Adjuvant Pelvic Radiation Following Prostatectomy

Ductal feature を有する前立腺癌の臨床的検討

To determine the incidence and prognosis of prostatic ductal adenocarcinoma. From November 2002 to December 2005, we performed 122 radical prostatectomies and pelvic lymph node dissections. We further analyzed 64 cases after excluding 56 cases that had received neoadjuvant hormone therapy and two cases for which we were only able to perform limited follow-up examinations. We reviewed all of the surgical specimens and reclassified them according to the 2004 WHO classification system. We differentiated prostatic cases of ductal adenocarcinoma that were larger than 5 mm in diameter from cases of acinar adenocarcinomas. We then examined these two groups for the pathological stages of the neoplasms and the incidence of postoperative prostate-specific antigen (PSA) failure. Postoperative PSA failure was defined as a PSA value more than 0.2 ng/ml. We found eight cases (12%) of prostatic ductal adenocarcinoma among the 64 cases treated with radical prostatectomies. The mean age (+/- SD) of these patients was 65.3 (+/- 4.3) years old, and the mean PSA level (+/- SD) was 12.4 (+/- 5.4) ng/ml. Seven of the cases (11%) were mixed-type ductal adenocarcinomas, which contained acinar and ductal components. In addition, one case was identified as pure ductal adenocarcinoma. Seminal vesicle invasion was detected in four cases and lymph nodes metastases were identified in one case. During the follow-up period, four of the eight cases of ductal adenocarcinoma (50%) and twelve of the 56 cases of acinar adenocarcinoma (21%) showed postoperative PSA failure. The median follow-up period was 24 months (range: 12 to 48 months). We identified eight cases of ducal adenocarcinoma (12% of the examined cases), which suggests this disease is not as rare as previously reported. Compared to the cases of acinar adenocarcinoma, the cases of ductal adenocarcinoma were at a more advanced pathological stage and resulted in a higher rate of postoperative PSA failure. Therefore, we believe that patients that show even a limited degree of ductal adenocarcinoma should receive aggressive therapy.

Maximal tumor diameter and the risk of PSA failure in men with specimen-confined prostate cancer

Objectives To evaluate whether the maximal tumor diameter (MTD) is significantly associated with the time to postoperative prostate-specific antigen (PSA) failure. Methods Between 1986 and 2002, 781 men with clinical Stage T1c–T2 prostate cancer underwent radical prostatectomy. The MTD was recorded as the maximal dimension of the largest single focus of cancer from all 3-mm step sections. The median follow-up was 5.4 years (range 0.1 to 14.9); 242 men (31%) experienced PSA failure. A Cox regression analysis was used to determine the predictors of time to postoperative PSA failure. Kaplan-Meier estimates of PSA failure-free survival were made, dichotomized about the median MTD value, and compared using a two-sided log-rank test. Results The value of the MTD was significantly associated with the time to PSA failure (adjusted hazard ratio 1.04, 95% confidence interval 1.01 to 1.07, P = 0.004), controlling for preoperative PSA level ( P <0.0001), prostatectomy Gleason score ( P <0.0001), and T stage ( P <0.0001). When margin status was added ( P = 0.0004), the MTD approached statistical significance ( P = 0.07). For patients with a preoperative PSA level of less than 10 ng/mL, prostatectomy Gleason score of 3 + 4 = 7 or less, Stage pT2–T3a, and negative margins, the value of the MTD significantly ( P = 0.05) stratified the time to PSA failure, when dichotomized about the median value (13 mm), with 7-year PSA failure estimates of 17% versus 8%. Conclusions Whether patients with traditionally low-risk but large MTD prostate cancer fare better when treated with adjuvant radiotherapy compared with salvage radiotherapy remains to be answered in the setting of a randomized trial.