Postoperative Prostate-specific Antigen Research Articles

Does seminal vesicle-sparing robotic radical prostatectomy influence postoperative prostate-specific antigen measured with an ultrasensitive immunoassay?

PURPOSE Sparing of the seminal vesicles during robotic radical prostatectomy (SVRP) is an attempt to reduce potential damage to the hypogastric pelvic nerves. However, the seminal vesicles are known to express prostate-specific antigen (PSA) and it is unknown whether SVRP influences oncological outcome measured with ultrasensitive PSA immunoassays. In a retrospective study we analysed whether SVRP affects oncological outcome in terms of ultrasensitive PSA nadir and biochemical recurrence as compared with standard robotic assisted laparoscopic radical prostatectomy (sRALP). METHODS Overall, 102 patients underwent robotic prostatectomy. Patients were non-randomly allocated to the following surgical techniques: a SVRP group of 39 patients who underwent robotic radical prostatectomy sparing the tips of the seminal vesicles; a standard group of 63 patients who were treated with sRALP. Inclusion criteria were histologically proven negative margins (R0) and negative lymph node status (pN0). PSA was measured with an ultrasensitive assay. The Mann-Whitney U-test was used to compare the differences in PSA nadir and follow-up PSA. Biochemical recurrence was diagnosed if PSA rose to ≥0.2 mg/ml. RESULTS Median (range) follow-up was 31.4 (16.4–43.8) months. Preoperative PSA was 5.8 (0.13–15.29) ng/ml in the SVRP group and 7.1 (0.8–46) ng/ml in the sRALP group. Two cases of biochemical recurrence occurred in the sRALP group during follow-up. One of these two patients presented with locally advanced prostate carcinoma diagnosed from the definitive pathological specimen (pT3b). No patient of the SVRP group had seminal vesicle invasion or biochemical recurrence. No significant between-group difference in terms of PSA nadir and follow-up PSA was recorded. However, the percentage of patients who did not reach PSA nadir values of <0.01 ng/ml was higher in the SVRP group (10 vs 5% in the sRALP group). CONCLUSIONS Compared with sRALP, SVRP had no clinical impact on oncological outcome in terms of PSA nadir or biochemical recurrence measured with an ultrasensitive PSA immunoassay. A slightly higher PSA nadir after SVRP seems to be expected, which needs to be mentioned during follow-up of these patients.

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.

Prediction of biochemical failure using prostate-specific antigen half-life in patients with adverse pathologic features after radical prostatectomy.

Prostate-specific antigen nadir and time to prostate-specific antigen nadir are predictors of disease progression in patients who undergo radical prostatectomy. However, a mutually conflicting relationship exists between them. Thus, we compared postoperative prostate-specific antigen levels at the first follow-up with the expected levels while considering the half-life of prostate-specific antigen to improve the prediction of biochemical failure after radical prostatectomy in patients with adverse pathologic features. Patients treated with robot-assisted laparoscopic prostatectomy were enrolled. Patients with a follow-up duration of < 12months or positive lymphadenectomy results were excluded. "Adverse prostate-specific antigen" was defined as a prostate-specific antigen level higher than the expected level at 6weeks. Among 450 patients, adverse pathologic features and adverse prostate-specific antigen were found in 260 (57.8%) and 245 (54.5%) patients, respectively. Analysis of patients with and without abnormal prostate-specific antigen level revealed significantly different biochemical failure-free survival outcomes. Patients with one adverse pathologic feature but without adverse prostate-specific antigen showed similar biochemical failure-free survival to those without adverse pathologic features. Adverse prostate-specific antigen was identified as an independent predictor for biochemical failure within 1year after radical prostatectomy. The area under the curve when adding adverse prostate-specific antigen to the conventional factors was significantly higher than that for the conventional factors alone. The difference between postoperative prostate-specific antigen levels at the first follow-up visit after radical prostatectomy and the expected level while considering the half-life of prostate-specific antigen is a predictive factor for treatment efficacy following radical prostatectomy.

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

Tailored postoperative treatment of prostate cancer: final results of a phase I/II trial

BackgroudThe European Organization for Research and Treatment of Cancer (EORTC) trial 22,911 reported 74% 5-year biochemical disease-free survival (bDFS) in patients with prostate carcinoma treated with radical prostatectomy (RP) followed by postoperative radiotherapy (RT). This study aimed to improve these outcomes by using a combined-intensified-modulated-adjuvant treatment, including RT and hormone therapy (HT) after RP.Materials and methodsThis phase I/II trial treatment was designed to improve 5-year bDFS from ~ 75 to 90%. Patients were consecutively enrolled using the following inclusion criteria: age < 80 years, histological diagnosis of prostate adenocarcinoma without known metastases, stage pT2-4N0-1, and Eastern Cooperative Oncology Group performance status of 0–2. All patients had at least one of these pathologic features: capsular perforation, positive surgical margins, seminal vesicle invasion, and pelvic lymph nodes involvement. A minimum dose of 64.8 Gy to the tumor bed was delivered in all patients. Depending on tumor characteristics at diagnosis, patients received a higher dose (70.2 Gy; 85.4%) and/or prophylactic pelvic lymph nodes irradiation (57.7%) and/or HT (69.1%). Biochemical relapse was defined as two consecutive rising prostate-specific antigen (PSA) values > 0.2 ng/ml.ResultsA total of 123 patients were enrolled in the study and completed the scheduled treatment. Median preoperative and postoperative PSA were: 8.8 and 0.06 ng/mL, respectively. The percentages of patients with pathologically involved nodes and positive resection margins were: 14.6% and 58.5%, respectively. With a median follow-up of 67 months (range: 37–120 months), the actuarial 5-year bDFS, local control, metastasis-free survival, and overall survival (OS) were: 92.9%, 98.7%, 96.1%, and 95.1%, respectively.ConclusionA higher 5-year bDFS (92.9%) was recorded compared to studies based on standard adjuvant RT, even though patients with nodal disease and detectable postoperative PSA were enrolled. Clinical end points, as long-term disease-free survival and OS, will require further assessments. (ClinicalTrials.gov: NCT03169933)

Oligometastatic prostate cancer and salvage lymph node dissection: systematic review.

We provide a comprehensive description of the physio-pathological theories behind oligometastatic prostate cancer (PCa) and analyze modern imaging techniques, presenting a systematic review of the available evidences regarding salvage lymph node dissection (sLND). A systematic review was attempted. The PubMed/Medline database was searched for "salvage" AND ("lymph node dissection" OR "lymphadenectomy") AND "prostate" AND "cancer." Only English publications were targeted. Relevant original articles addressing the role of sLND in PCa were selected. Biochemical response (BR) was reported in 10-79.5% of the cases overall. These results were not durable and biochemical recurrence occurred in 54.5-93.8% of the cases, within 5 years. Furthermore, 50-80% of patients received some kind of adjuvant treatment right after sLND, regardless post-operative prostate-specific antigen levels. Surgery-related morbidity was low, with a 0-27% incidence of Clavien-Dindo III complications. No sLND-related deaths were observed. sLND is not associated with a durable response over time but may postpone HT and its related complications, in selected patients. Although a limited morbidity was reported, sLND remains technically demanding and a careful selection of patients is advisable.

Primary whole-gland ablation for localized prostate cancer with high-intensity focused ultrasound: The important predictors of biochemical recurrence.

To identify predictive factors of biochemical recurrence for patients undergoing high-intensity focused ultrasound treatment for localized prostate cancer. We retrospectively identified patients receiving whole-gland prostate ablation with high-intensity focused ultrasound for localized prostate cancer from 2009 to 2015. All the patients received pre-high-intensity focused ultrasound radical transurethral resection of the prostate. We included perioperative parameters as follows: age, preoperative prostate volume, stage of operation, initial prostate-specific antigen, T stage, postoperative prostate-specific antigen nadir, Gleason score, time to prostate-specific antigen nadir and the presence of prostate-specific antigen biochemical recurrence. Multivariable Cox regression and Kaplan-Meier analysis were used for investigating predictors of recurrence, and receiver operating characteristic analysis was used for the cut-off values of prostate-specific antigen nadir. Among 182 patients, 26.9% had prostate-specific antigen biochemical recurrence after high-intensity focused ultrasound during the median follow-up period of 32.21 months. Gleason score ≥7 (Gleason score 7, hazard ratio 2.877, P = 0.027), stage ≥T2b (T2b, hazard ratio 3.16, P = 0.027) and prostate-specific antigen nadir (hazard ratio 1.11, P < 0.001) were statistically significant, whereas there was no significance in prostate volume and initial prostate-specific antigen. We posit that a cut-off level of prostate-specific antigen nadir 0.43 ng/mL might be considered as an independent predictive factor for prostate-specific antigen biochemical recurrence in high-intensity focused ultrasound patients in multivariate analysis (P < 0.001, hazard ratio 7.39, 95% confidence interval 3.56-15.37), and created a new nadir-related prediction model for biochemical recurrence prediction. Postoperative prostate-specific antigen nadir of 0.43 ng/mL can be considered an important predictive factor for biochemical recurrence in primary whole-prostate gland high-intensity focused ultrasound treatment, and the nadir-related prediction model might provide a reference for early salvage treatment. Furthermore, Gleason score ≥7, stage ≥T2b might be associated with unfavorable outcomes, although prostate volume and higher initial prostate-specific antigen appear not to be associated with biochemical recurrence for the high-intensity focused ultrasound treatment.

Predictive Factors of Biochemical Recurrence in Positive Surgical Margin Patients by Radical Prostatectomy

The predictive factors for biochemical recurrence (BCR) were investigated in patients with positive surgical margin of the extirpated prostate by radical retropubic prostatectomy (RRP). The records of 365 patients who underwent RRP in our hospital between January 2002 and December 2014 were retrospectively analyzed. Patients who had received additional therapy before or after RRP, who had not been followed up for more than a year after surgery, and who had pN1 lesions were excluded from the study. Positive surgical margin was observed in 112 cases. Prostate specific antigen (PSA) before surgery ≥20 ng/ml, biopsy positive core ratio ≥40%, Gleason score of the surgical specimen ≥8, and postoperative PSA nadir ≥0.01 ng/ml were identified as significant predictors of BCR.

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.

Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy

BackgroundProstate cancer patients who have a detectable prostate-specific antigen (PSA) postprostatectomy may harbor pre-existing metastatic disease. To our knowledge, none of the commercially available genomic biomarkers have been investigated in such men. ObjectiveTo evaluate if a 22-gene genomic classifier can independently predict development of metastasis in men with PSA persistence postoperatively. Design, setting, and participantsA multi-institutional study of 477 men who underwent radical prostatectomy (RP) between 1990 and 2015 from three academic centers. Patients were categorized as detectable PSA (n=150) or undetectable (n=327) based on post-RP PSA nadir ≥0.1 ng/ml. Outcome measurements and statisitical analysisCumulative incidence curves for metastasis were constructed using Fine-Gray competing risks analysis. Penalized Cox univariable and multivariable (MVA) proportional hazards models were performed to evaluate the association of the genomic classifier with metastasis. Results and limitationsThe median follow-up for censored patients was 57 mo. The median time from RP to first postoperative PSA was 1.4 mo. Detectable PSA patients were more likely to have higher adverse pathologic features compared with undetectable PSA patients. On MVA, only genomic high-risk (hazard ratio [HR]: 5.95, 95% confidence interval [CI]: 2.02–19.41, p=0.001), detectable PSA (HR: 4.26, 95% CI: 1.16–21.8, p=0.03), and lymph node invasion (HR: 12.2, 95% CI: 2.46–70.7, p=0.003) remained prognostic factors for metastasis. Among detectable PSA patients, the 5-yr metastasis rate was 0.90% for genomic low/intermediate and 18% for genomic high risk (p<0.001). Genomic high risk remained independently prognostic on MVA (HR: 5.61, 95% CI: 1.48–22.7, p=0.01) among detectable PSA patients. C-index for Cancer of the Prostate Risk Assessment Postsurgical score, Gandaglia nomogram, and the genomic classifier plus either Cancer of the Prostate Risk Assessment Postsurgical score or Gandaglia were 0.69, 0.68, and 0.82 or 0.81, respectively. Sample size was a limitation. ConclusionsDespite patients with a detectable PSA harboring significantly higher rates of aggressive clinicopathologic features, Decipher independently predicts for metastasis. Prospective validation of these findings is warranted and will be collected as part of the ongoing randomized trial NRG GU-002. Patient summaryDecipher independently predicted metastasis for patients with detectable prostate-specific antigen after prostatectomy.

Functional Recovery, Oncologic Outcomes and Postoperative Complications after Robot-Assisted Radical Prostatectomy: An Evidence-Based Analysis Comparing the Retzius Sparing and Standard Approaches

We report a 1-year update of functional urinary and sexual recovery, oncologic outcomes and postoperative complications in patients who completed a randomized controlled trial comparing posterior (Retzius sparing) with anterior robot-assisted radical prostatectomy. A total of 120 patients with clinically low-intermediate risk prostate cancer were randomized to undergo robot-assisted radical prostatectomy via the posterior and anterior approach in 60 each. Surgery was performed by a single surgical team at an academic institution. An independent third party ascertained urinary and sexual function outcomes preoperatively, and 3, 6 and 12 months after surgery. Oncologic outcomes consisted of positive surgical margins and biochemical recurrence-free survival. Biochemical recurrence was defined as 2 postoperative prostate specific antigen values of 0.2 ng/ml or greater. Median age of the cohort was 61 years and median followup was 12 months. At 12 months in the anterior vs posterior prostatectomy groups there were no statistically significant differences in the urinary continence rate (0 to 1 security pad per day in 93.3% vs 98.3%, p = 0.09), 24-hour pad weight (median 12vs 7.5 gm, p = 0.3), erection sufficient for intercourse (69.2% vs 86.5%) or postoperative Sexual Health Inventory for Men score 17 or greater (44.6% vs 44.1%). In the posterior vs anterior prostatectomy groups a nonfocal positive surgical margin was found in 11.7% vs 8.3%, biochemical recurrence-free survival probability was 0.84 vs 0.93 and postoperative complications developed in 18.3% vs 11.7%. Among patients with clinically low-intermediate risk prostate cancer randomized to anterior (Menon) or posterior (Bocciardi) approach robot-assisted radical prostatectomy the differences in urinary continence seen at 3 months were muted at the 12-month followup. Sexual function recovery, postoperative complication and biochemical recurrence rates were comparable 1 year postoperatively.

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

Does Early Prostate Specific Antigen Doubling Time after Radical Prostatectomy, Calculated Prior to Prostate Specific Antigen Recurrence, Correlate with Prostate Cancer Outcomes? A Report from the SEARCH Database Group

Short prostate specific antigen doubling time following recurrence after radical prostatectomy portends a poor prognosis. Prostate specific antigen doubling time is traditionally calculated using prostate specific antigen values 0.2 ng/ml or greater. We determined whether early prostate specific antigen doubling time, calculated from the first detectable postoperative prostate specific antigen up to and including the first recurrence value, correlates with prostate cancer outcomes. Cox models were used to examine the association between early prostate specific antigen doubling time and castration resistant prostate cancer, metastases, and all cause and prostate cancer specific mortality in 674 men who underwent radical prostatectomy between 1988 and 2014 and had a biochemical recurrence. Early prostate specific antigen doubling time was examined as a log transformed continuous and a categorical variable. After adjusting for multiple clinicopathological characteristics, log transformed early prostate specific antigen doubling time was not associated with any outcome. However, when early doubling time was categorized as 15 or greater, 9 to 14.9, 3 to 8.9 and less than 3 months, on multivariable analysis men with early doubling time less than 3 months were at increased risk for castration resistant prostate cancer (HR 6.20, p = 0.004), metastases (HR 5.26, p = 0.001), prostate cancer specific mortality (HR 5.06, p = 0.026) and all cause mortality (HR 1.63, p = 0.065) compared to those with an early doubling time of 15 months or greater. However, the association with all cause mortality was not significant. Those with an early prostate specific antigen doubling time of 3 to 8.9 months were at increased risk for castration resistant prostate cancer (HR 3.56, p = 0.015), all cause mortality (HR 1.67, p = 0.006) and prostate cancer specific mortality (HR 3.17, p = 0.044) but not metastases (p = 0.13). Early prostate specific antigen doubling time less than 9 months, calculated using prostate specific antigen values before and up to biochemical recurrence, is associated with an increased risk of castration resistant prostate cancer, metastases, and prostate cancer specific and all cause mortality among men with biochemical recurrence after radical prostatectomy. Early prostate specific antigen doubling timeallows for risk stratification at biochemical recurrence and before prostate specific antigen doubling timeis calculable, enabling these men to be referred for early aggressive secondary treatment and/or clinical trials.

Timing of Prostate-specific Antigen Nadir After Radical Prostatectomy and Risk of Biochemical Recurrence

To evaluate the association between the prostate-specific antigen (PSA) nadir level and the time to nadir (TTN) with biochemical recurrence (BCR) risk after radical prostatectomy (RP) in the Shared Equal-Access Research Cancer Hospital (SEARCH) database. This is a retrospective analysis of 1939 men from the SEARCH database treated with RP between 1998 and 2015 with available ultrasensitive PSA nadir within 1-6 months after RP. Uni- and multivariable analyses of PSA nadir and TTN with time from nadir to BCR were performed with Cox models (adjusted for demographics, tumor features, and preoperative PSA). Among men with an undetectable PSA nadir, the TTN was unrelated to BCR (1.0-2.9 vs 3-6 months: hazard ratio [HR] 0.86, P = .46). Regardless of TTN, men with detectable nadir had an increased risk of BCR (TTN of 3-6 months: HR 1.81, P = .024; TTN of 1.0-2.99 months: HR 3.75, P <.001 vs undetectable nadir and TTN of 3-6 months). Among men with a detectable PSA at 1-3 months, 53% had a lower PSA level during follow-up 3-6 months after RP, which was undetectable in 32% and lower but still detectable in 21%. In the post-RP setting, men with both a detectable nadir and a shorter TTN had an increased risk of BCR. Intriguingly, about half of the men with a detectable PSA in the first 3 months after RP had a lower PSA level during follow-up between 3 and 6 months after RP. If confirmed in future studies, this has important implications for patients considering adjuvant therapy based on postoperative PSA values in the first 3 months after RP.

Prospective evaluation of computer-assisted analysis of skeletal lesions for the staging of prostate cancer

BackgroundThe purpose of this study was to compare the agreement of the bone scan index (BSI) using EXINI BoneBSI versus experts’ readings in the initial staging for bone metastasis in prostate cancer. In addition, the diagnostic outcome was assessed in a large subset of patients where a true reference for metastases could be determined based on clinical and biochemical follow-up and/or supplementary imaging.MethodsA total of 342 patients had a bone scintigraphy as part of routine staging for prostate cancer. Supplementary imaging was obtained at the discretion of the referring urologist. After full recruitment, the BSI and the number of malignant lesions were calculated using EXINI BoneBSI, and three imaging experts independently classified bone status by a dichotomous outcome (M1 for bone metastasis, M0 for no bone metastasis). A true reference was available in a subset of the patients based on post-operative prostate-specific antigen responses after radical prostatectomy and/or supplementary imaging.ResultsSoftware analysis with a BSI > 0 as the cut-off for metastasis showed excellent agreement with expert classification for M1 disease (96% of the patients) but modest agreement for M0 disease (38%). With a BSI > 1, the agreement was 58% for M1 and 98% for M0. Software analyses based on individual European Association of Urology risk classification did not improve the diagnostic performance. Among patients with a true reference, the software showed metastasis in 64% of the M0 patients but correctly classified metastases in all M1 patients. The sensitivity was 100%, the specificity was 36%, the positive predictive value was 12.6% and the negative predictive value was 100% with a BSI >0 compared with 66.7%, 97.8%, 72.7%, and 97.0% with a BSI > 1.ConclusionThe diagnostic value of using EXINI Bone for the BSI in the staging of newly diagnosed prostate cancer is limited.

Radiotherapy of prostate cancer

Radiotherapy(RT) is one of the principle treatment options for prostate cancer. Modern RT and surgery show similar progression-free survival in localized prostate cancer. Adjuvant RT compared to observation significantly diminishes the risk of prostate-specific antigen(PSA) progression and local failure for patients at the highest risk for recurrence after radical prostatectomy, including with seminal vesicle invasion, extraprostatic extension, extensive positive margins, and detectable postoperative PSA. Salvage RT is effective at controlling local recurrence and reduces the risk of distant metastasis and prostate cancer-specific mortality (PCSM) for patients with PSA or local recurrence after prostatectomy. Hypofractionated radiotherapy of recent years' reports shows similar cancer control rates without an increased risk of late toxicity in comparison to conventional regimens. The addition of androgen-deprivation therapy(ADT) to radiation improves the overall survival and biochemical progression-free survival(bPFS) for intermediate-risk and high-risk patients. Key words: Prostatic neoplasms; Radiotherapy(RT); Adjuvant radiotherapy; Salvage radiotherapy; Hypofractionated radiotherapy

Impact of Postoperative Radiotherapy in Men with Persistently Elevated Prostate-specific Antigen After Radical Prostatectomy for Prostate Cancer: A Long-term Survival Analysis

BackgroundProstate cancer (PCa) patients with prostate-specific antigen (PSA) persistence after radical prostatectomy (RP) are at increased risk of mortality, although the natural history of these men is heterogeneous and the optimal management has not been established. ObjectiveTo develop a model to predict cancer-specific mortality (CSM) and to test the impact of radiotherapy (RT) on survival in this setting. Design, setting, and participantsWe identified 496 patients treated with RP and lymph node dissection at two referral centers between 1994 and 2014 who had PSA persistence, defined as a PSA level between 0.1 and 2 ng/ml at 6–8 wk after RP. Outcome measurements and statistical analysesA multivariable model predicting CSM was developed. We assessed whether the impact of postoperative PSA levels on survival differed according to baseline CSM risk. The nonparametric curve fitting method was then used to explore the relationship between baseline CSM risk and 10-yr CSM rates according to postoperative RT. Results and limitationsMedian follow-up for survivors was 110 mo. Overall, 49 patients experienced CSM. The 10-yr CSM-free survival was 88%. Pathologic grade group and pathologic stage were independent predictors of CSM (all p=0.01). The association between CSM-free survival and PSA at 6–8 wk differed by the baseline CSM risk, whereby the effect of increasing PSA was evident only in patients with a CSM risk of ≥10%. Postoperative RT was beneficial when the predicted risk of CSM was ≥30% (p=0.001 by an interaction test). Our study is limited by its retrospective design. ConclusionsIncreasing PSA levels should be considered as predictors of mortality exclusively in men with worse pathologic characteristics. Postoperative RT in this setting was associated with a survival benefit in patients with a CSM risk of ≥30%. Conversely, individuals with a CSM risk of <30% should be initially managed expectantly. Patient summaryNot all patients with prostate-specific antigen persistence have a poor prognosis. Pathologic characteristics should be used to estimate the risk of cancer-specific mortality in these individuals and to identify patients who could benefit from postoperative radiotherapy.

Prognostic variables associated with biochemical recurrence following radical prostatectomy for pT3b prostate cancer: a research study

Objectives: The objectives of the current study were to determine long-term biochemical recurrence rates stratified by adverse pathologic features and to identify predictive factors of biochemical recurrence rates following radical prostatectomy performed by either retropubic prostatectomy or robot-assisted laparoscopic prostatectomy from single tertiary center prostate cancer database. Material and Methods: The Seoul National University Hospital prostate cancer database was queried for all patients treated with radical prostatectomy from 1999 to 2015. Among the 2680 patients who underwent radical prostatectomy, 331 patients with seminal vesicle invasion (pathologic T3bN0-1M0 stage) were identified. The primary endpoint was biochemical recurrence, defined as two consecutive postoperative prostate specific antigen values ≥0.2 ng/ml. Comparative analysis based on adverse pathologic characteristics and operation type was performed. Results: Five and 10-year biochemical recurrence-free survival in the entire cohort was 59.0% and 42.9%. The Kaplan-Meier survival analysis demonstrated 5-year biochemical recurrence free survival rates differences in patients with different lymph node involvement (70.6% vs. 52.4%, log-rank, p=0.01). Variables including age, extracapsular extension, lymph node invasion, surgical margin, perineural invasion, multicentricity and Capra-S score were similar between the groups of patients who underwent either retropubic or robot-assisted laparoscopic radical prostatectomy. The mean prostate specific antigen level, seminal vesicle invasion laterality, tumor volume, and pathologic Gleason score were lower in the cohort of patients who underwent robot-assisted laparoscopic prostatectomy. No statistically significant differences were found in 5-year biochemical recurrence-free survival rates stratified by operation type (58.1% vs. 65%, log-rank, p=0.8), by Capra-S score (72.5% vs. 56.8%, log rank, p=0.1), or by surgical margin status (69.4% vs. 59.3%, log-rank, p=0.8). In univariate and multivariate Cox proportional regression analysis lymph node involvement (p=0.01) was found to be a statistically significant predictor of biochemical recurrence. Conclusion: Patients with positive lymph node involvement have a poor prognosis. Capra-S score was unable to predict biochemical recurrence in patients with pathologic T3b stage prostate cancer. Robot-assisted laparoscopic prostatectomy is comparable to retropubic radical prostatectomy in terms of the biochemical progression of prostate cancer with seminal vesicle invasion.

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.

Moderate Hypofractionated Postprostatectomy Volumetric Modulated Arc Therapy With Daily Image Guidance (VMAT-IGRT): AMono-institutional Report on Feasibility and Acute Toxicity.

The aim of this study was to evaluate the acute toxicity profiles of a moderate hypofractionated regimen with volumetric modulated arc therapy (VMAT) in patients with prostate cancer (PC) who underwent radical prostatectomy. From December 2012 to February 2016, 125 patients, previously having undergone radical prostatectomy, received adjuvant (64 patients) or salvage (61 patients) radiotherapy (RT) inside an institutional protocol of moderate hypofractionation schedule using the VMAT technique (Varian RapidArc, Palo Alto, CA). Eligible patients were< 85 years old, with an Eastern Cooperative Oncology Group performance status of 0 to 2, histologically proven adenocarcinoma of the prostate without distant metastases, and pathologic stage pT2-4 N0-1, with at least 1 of the following risk factors: capsular perforation, positive surgical margins, seminal vesicle invasion, and/or postoperative prostate-specific antigen > 0.2 ng/mL. Patients were stratified into low (1%), intermediate (9%), and high-risk (90%) groups. The median age was 68 years. The median doses were 66 Gy (range, 65.5-71.4 Gy) to the prostatic bed and 52.5 Gy (range, 50.4-54 Gy) to the pelvic lymph nodes, in 28 or 30 fractions. The acute genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Common Terminology Criteria for Adverse Events, v4. All 125 patients completed the planned treatment, with good tolerance. After RT, the median follow-up was 18 months. Acute toxicities were recorded for the GU (G0, 45/125 [36%]; G1, 63/125 [50.4%]; G2, 16/125 [12.8%]; G3, 1/125 [0.8%]) and the GI (G0, 42/125 [33.6%]; G1, 72/125 [57.6%]; G2, 11/125 [8.8%]; no G3). Analyzing data according to RT intent, a higher rate of GU toxicity≥ 2 was found in the adjuvant setting (17.1%) with respect to the salvage group (9.8%); P= .01 with the Fisher exact text. Furthermore, at statistical analysis, no difference was found between the type of surgery (robotic, laparoscopic, or open) and incidence of urinary incontinence (P= .8). The actuarial Kaplan-Meier rates for biochemical disease-free survival were 94% and 77% for adjuvant and salvage RT, at 36 months. Moderate hypofractionated postoperative RT with VMAT was feasible and safe with acceptable acute GU and GI toxicities. Longer follow-up is needed to assess late toxicity and clinical outcomes.