Postoperative Biochemical Failure Research Articles

A preoperative magnetic resonance imaging-based model to predict biochemical failure after radical prostatectomy

To investigate if a magnetic resonance imaging (MRI)-based model reduced postoperative biochemical failure (BF) incidence in patients with prostate cancer (PCa). From June 2018 to January 2020, we retrospectively analyzed 967 patients who underwent prostate bi-parametric MRI and radical prostatectomy (RP). After inclusion criteria were applied, 446 patients were randomized into research (n = 335) and validation cohorts (n = 111) at a 3:1 ratio. In addition to clinical variables, MRI models also included MRI parameters. The area under the curve (AUC) of receiver operating characteristic and decision curves were analyzed. The risk of postoperative BF, defined as persistently high or re-elevated prostate serum antigen (PSA) levels in patients with PCa with no clinical recurrence. In the research (age 69 [63–74] years) and validation cohorts (age 69 [64–74] years), the postoperative BF incidence was 22.39% and 27.02%, respectively. In the research cohort, the AUC of baseline and MRI models was 0.780 and 0.857, respectively, with a significant difference (P < 0.05). Validation cohort results were consistent (0.753 vs. 0.865, P < 0.05). At a 20% risk threshold, the false positive rate in the MRI model was lower when compared with the baseline model (31% [95% confidence interval (CI): 9–39%] vs. 44% [95% CI: 15–64%]), with the true positive rate only decreasing by a little (83% [95% CI: 63–94%] vs. 87% [95% CI: 75–100%]). 32 of 100 RPs can been performed, with no raise in quantity of patients with missed BF. We developed and verified a MRI-based model to predict BF incidence in patients after RP using preoperative clinical and MRI-related variables. This model could be used in clinical settings.

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.

Factors Predicting Prostate Specific Antigen Failure Following Radical Prostatectomy: Experience with 961 Patients.

To determine disease-related predictors for the occurrence of prostate specific antigen (PSA) failure in Iranian prostate cancer patients who underwent radical prostatectomy. In this cohort study, we enrolled eligible patients with prostate cancer who underwent radical prostatectomy at our center between 2001 and 2018. The primary endpoint was the incidence of postoperative biochemical failure, defined as two consecutive PSA levels >= 0.2 ng/dl. Patients with TNM stage >= III, Gleason score >=8, or baseline PSA above our calculated cut-off level were considered as high risk. Kaplan-Meier survival method and Cox proportional hazards regression analysis were used for determining the biochemical relapse-free survival and its predictors. Data of 959 patients (age=61.2 ± 6.4 years) were analyzed with a median follow up of 36 months (range 6 months to 18 years). A total of 97 patients (10.1%) developed biochemical failure at the time of analysis who had a significantly older age and longer follow-up duration (P=0.024 and P<0.001, respectively). Preoperative PSA level of 8.85 mg/dl could predict the occurrence biochemical failure with a sensitivity of 83.2% and specificity of 39.2% (Area under the curve=0.601, 95% CI: 0.541-0.662; P=0.001). In the multivariate analysis, higher preoperative PSA, Gleason score?8, and high-risk TNM stage were independent predictors for biochemical relapse (P=0.029, P=0.001, and P=0.008, respectively). Preoperative PSA, Gleason score, and TNM stage were independent predictors for biochemical failure following radical prostatectomy in prostate cancer patients. We also determined a lower cut-point for PSA that could predict biochemical failure.

Risk adapted dose-intensified postoperative radiation therapy in prostate cancer patients using a simultaneous integrated boost technique applied with helical Tomotherapy

BackgroundPostoperative adjuvant radiation therapy (ART) in T3 and R1 prostate cancer as well as salvage radiation therapy (SRT) in case of postoperative biochemical failure (BF) are established treatments. Dose-intensified postoperative radiation therapy (RT) schemes have shown superior biochemical control accompanied by increased toxicity rates. In our study we evaluate a novel risk adapted dose-intensified postoperative RT scheme.MethodsA consecutive series of prostate cancer patients receiving postoperative RT after radical prostatectomy using helical Tomotherapy between 04/2012 and 04/2015 was analyzed retrospectively. RT was administered using a simultaneous integrated boost (SIB) to the area at risk (37 fractions of 1.9 Gy, total dose: 70.3 Gy) being defined based on histopathological findings (T3/R1 region) and in few cases according to additional diagnostic imaging. The whole prostate bed was treated with a dose of 66.6 Gy (37 fractions of 1.8 Gy). Primary endpoints were acute and late genitourinary (GU) and gastrointestinal (GI) toxicities. Secondary endpoints included patient reported outcome as assessed by the International Prostate Symptom Score (IPSS), the International Consultation on Incontinence questionnaire (ICIQ) and prostate cancer specific Quality of Life questionnaire QLQ-PR25, as well as rates of BF.ResultsA total of 69 patients were analyzed. Sixteen patients underwent ART and 53 patients SRT, respectively. The median follow-up was 20 months (range, 8–41 months). Seven (10.1%) and four (5.8%) patients experienced acute grade 2 GU and GI toxicity. Two patients (2.9%) had late grade 2 GU toxicity, whereas no late grade 2 GI nor any grade 3 acute or late GU or GI events were observed. When compared to the baseline IPSS scores (p = 1.0) and ICIQ scores (p = 0.87) were not significantly different at the end of follow-up. Patient reported Quality of life (QoL) showed also no significant difference. A total of seven patients (10.1%) experienced a biochemical recurrence with the 2-year biochemical progression-free survival (bPFS) being 91%.ConclusionsPostoperative RT for prostate cancer patients with a risk adapted dose-intensified SIB using helical tomotherapy is feasible and associated with favorable acute and late GU and GI toxicity rates, no significant change of IPSS-, ICIQ scores and patient reported QoL and results in promising bPFS rates.

Whole pelvic irradiation for prostate cancer patients with a biochemical relapse following radical prostatectomy: The era of robot-assisted minimally invasive surgery.

210 Background: We hypothesized that the addition of whole pelvic radiotherapy (WPRT) might improve biochemical outcome in salvage radiotherapy (RT) for biochemical failure (BCF), especially in patients with postoperative high-risk features after radical prostatectomy (RP) being good candidates beneficial from WPRT. Methods: From August 2004 to April 2012, 180 patients who experienced BCF after RP were treated with salvage RT. The primary end point was the biochemical relapse-free survival (bRFS) defined as no prostate-specific antigen (PSA) failure and no additional salvage treatments. Patients were stratified into theee groups; prostate bed radiotherapy (PBRT) alone (n = 52), PBRT with hormone (n = 85), and WPRT with hormone (n = 43). The effects of WPRT combined with hormone was measured in the high-risk patients defined as pN1 stage or inadequate pelvic lymph node dissection (harvested lymph nodes number of less than four). Toxicity from treatment was recorded when genitourinary or gastrointestinal (GI) events occurred. Results: The median follow-up was 43 months (8 to 103 months). The independent predictors for poor bRFS were time to PSA failure less than or equal to 1 year, PSA at salvage greater than 1 ng/mL, PSA doubling time less than 6 months, and PBRT alone group. The risk of BCF after salvage RT was significantly higher in PBRT alone group in comparison to that of WPRT with hormone group (hazard ratio [HR], 3.9; 95% CI, 1.8-8.3, p &lt;0.001), but the outcomes of PBRT with hormone was not statistically different from that of WPRT with hormone (p = 0.67). The advantage of WPRT and hormone over PBRT alone was only observed in the high-risk patients (HR, 5.7; 95% CI, 1.8-17.7, p = 0.003), and not in other patients (HR, 3.2; 95% CI, 0.7-14.9. p = 0.14). Patient treated with WPRT had more greater than or equal to grade 2 late GI toxicity than those having PBRT (17% vs. 5%, p= 0.01). Conclusions: Patients with postoperative high risk features could benefit from WPRT and hormone therapy for postoperative BCF. The additional toxicity by WPRT and long-term outcomes warrant further investigations.

Pathological Effects of Prostate Cancer Correlate With Neuroendocrine Differentiation and PTEN Expression After Bicalutamide Monotherapy

Androgen deprivation therapy is the primary treatment for advanced prostate cancer but many patients eventually experience progression to hormone refractory status. Understanding the molecular changes after androgen deprivation therapy would help evaluate the efficacy or failure of second line therapies. Therefore, we analyzed the expression of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN), the human epidermal receptor-2 and neuroendocrine differentiation after bicalutamide monotherapy, which is emerging as an alternative treatment for locally advanced prostate cancer. Molecular arrangements were evaluated in 107 radical prostatectomy specimens from patients given 150 mg bicalutamide before surgery. Pathological regressive changes, and the correlation of postoperative biochemical failure with the extent of molecular arrangements and pathological effects were analyzed. Patients with minimal regression effects after bicalutamide therapy had advanced pathological stage disease, and tended to have positive chromogranin A expression and PTEN inactivation. Only 4 (3.7%) prostatectomy specimens showed human epidermal receptor-2 immunostaining. The probability of positive chromogranin A expression in the PTEN inactivation group was 2.5-fold (OR 2.5, 95% CI 1.1-5.6, p = 0.023) higher than in the nonPTEN inactivation group. Cox regression analysis revealed that seminal vesicle invasion, PTEN/chromogranin A expression and lymph node invasion were significant variables for time to biochemical recurrence. PTEN inactivation and neuroendocrine differentiation were related to refractoriness to bicalutamide therapy. These results support the hypothesis that neuroendocrine differentiation is caused by activation of the serine threonine kinase Akt pathway, which results from PTEN inactivation.

Percentage of Cancer in Prostate Biopsies as Prognostic Factor for Staging and Postoperative Biochemical Failure after Radical Prostatectomy

Objective: To assess if the percentage of cancer in prostate needle biopsies provides independent prognostic information for predicting pathological stage and/or biochemical relapse after radical prostatectomy. Methods: One hundred and forty prostate cancer patients who underwent radical prostatectomy were evaluated. Preoperative parameters analyzed were patient age, PSA, clinical stage, and the information obtained from sextant biopsies (Gleason score, maximum percentage of cancer in a core, percentage of tissue with cancer in all biopsies and the number of cores positive for cancer). Univariate and multivariate analyses (logistic regression) for the dependent variables (prostate cancer, organ-confined and biochemical relapse) were performed. Results: The tumor was organ-confined in 73.6% of patients. In those patients studied for disease progression (n = 126), no biochemical recurrence was observed in 76.2%. In the multivariate analysis for organ-confined disease, the total percentage of biopsy tissue with cancer, the preoperative PSA level, the Gleason score and the clinical stage were the most accurate predictive factors of pathological stage. The multivariate analysis for the study of biochemical failure indicated that only the total percentage of biopsy tissue with cancer, the preoperative PSA level and the Gleason score were independent predictive factors. According to the logistic regression analysis for disease recurrence, 3 risk groups could be identified: low risk (less than 10% probability of disease progression), intermediate risk (30%) and high risk (more than 70%). Conclusions: The percentage of cancer in prostate biopsy provides independent prognostic information for predicting pathological stage and the risk of biochemical failure after radical prostatectomy.

Characterization of Biochemical Recurrence after Radical Prostatectomy

Background: This study sought to characterize the variables that predict postoperative prostate-specific antigen doubling time (PSADT) and biochemical recurrence time (RT) in patients who have failed radical prostatectomy (RP). Methods: A total of 477 patients underwent RP at our institution for clinically localized prostate cancer. Of these patients, 64 (13.4%) demonstrated evidence of postoperative biochemical failure. PSADT and biochemical RT were calculated for all patients. PSADT and RT were correlated with clinical variables including preoperative PSA level, patient age, race, prostate weight and with pathologic characteristics of the operative specimen using uni- and multivariate analyses. In addition, PSADT and RT were also correlated with each other and with the time to postoperative adjuvant therapy. Results: Median postoperative PSADT for patients who recurred after radical prostatectomy was 9.7 months. Postoperative PSADT was predicted by lymph node involvement (p < 0.001) and Gleason grade (p = 0.06). Rapid PSADT also correlated with institution of postoperative adjuvant therapy (p = 0.003). Median biochemical RT for all patients was 6.7 months. Gleason grade and pathologic stage were found to be predictors of RT (p < 0.002). Postoperative PSADT did not correlate with RT (r = 0.08; p = 0.53). PSADT and RT were not different between Caucasian- versus African-Americans. Conclusions: These results serve to better characterize our cohort of patients who have evidence of biochemical recurrence after radical prostatectomy. Aggressiveness of recurrent disease (i.e. PSADT) seems to be predicted by lymph node involvement and higher pathologic grade. Furthermore, the lack of correlation of RT and PSADT suggests that early recurrences are not necessarily aggressive tumors: conversely, aggressive recurrences may occur at any point in the postoperative period. This information may aid in the postoperative treatment of recurrent disease and help to better define those patients who are at higher risk for developing clinical recurrence and who would benefit from greater vigilance during the postoperative period.

ハイリスク前立腺癌に対する術前8ヵ月ネオアジュバント内分泌療法の有用性に関する検討

To evaluate the clinicopathological outcomes of 8 months of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy for high-risk prostate cancer. A multi-institutional prospective trial was performed between July 2000 and May 2003 involving high-risk prostate cancer patients without metastasis, including 21 who received 8 months of NHT before radical prostatectomy. High-risk group was defined as clinical stage > or =T2c and/or prostate-specific antigen (PSA) >20 ng/ml and/or Gleason score > or =8. PSA values were considered elevated (biochemical failure) if values of 0.1 ng/ml or greater were obtained. Median of initial PSA levels before prostate biopsy was 27.6 ng/ml (8.5-80.7 ng/ml), and median of pre-operative PSA levels after NHT was 0.28 ng/ml (0.02-4.2 ng/ml). There were 5 patients (23.8%) with lower limit of PSA detection (less than 0.02 ng/ml) in 8 months after NHT. The clinical T stage was T1c in 9 patients (42.9%), T2a-b in 8 patients (38.1%), T2c in 3 patients (14.3%), and T3a in 1 patient (4.8%). The median follow-up was 25 months (range 4 to 37). There were 2 patients (9.5%) in pT0, 5 patients (23.8%) with positive surgical margin, 5 patients (23.8%) with extracapsular extension (ECE) and 3 patients (14.3%) with seminal vesicle involvement (SVI). Biochemical failure was occurred in 9 of 21 (42.9%) including of one pT0. Range of time to postoperative biochemical failure was 2 to 25 months (median 6 months) and most of biochemical failure was found within 12 months after surgery. Biochemical failure rate was significantly higher in patient with positive SVI (p = 0.0308) and higher in patients with pre-operative PSA levels of more than 0.1 ng/ml (p = 0.0836), positive ECE (p = 0.0545) and positive surgical margin (p = 0.0545). Biochemical failure was frequent after this combined treatment, even in a pT0 case. Long-term follow-up of patients is needed to assess the impact of this therapy on mortality.

PSA Doubling Time as a Predictor of Clinical Progression After Biochemical Failure Following Radical Prostatectomy for Prostate Cancer

PSA Doubling Time as a Predictor of Clinical Progression After Biochemical Failure Following Radical Prostatectomy for Prostate Cancer

PSA Doubling Time as a Predictor of Clinical Progression After Biochemical Failure Following Radical Prostatectomy for Prostate Cancer

To characterize the clinical progression of disease in men who have undergone prostatectomy for clinically localized prostate cancer and have postoperative biochemical failure (elevated prostate-specific antigen [PSA] level) and to identify predictors of clinical disease progression, including the possible effect of PSA doubling time (PSADT). Between 1987 and 1993, 2809 patients underwent radical retropubic prostatectomy for clinically localized (< or =T2) disease. In our database, all patients with postoperative biochemical failure (PSA level > or =0.4 ng/mL) were identified. The PSADT was estimated using log linear regression on all PSA values (excluding those values determined after administration of hormonal therapy) within 15 months after biochemical failure. All patients had regular PSA measurements from the time of surgery through the follow-up period. Systemic progression (SP) was defined as evidence of metastatic disease on a bone scan. Local recurrence (LR) was defined on the basis of digital rectal examination, transrectal ultrasonography, and biopsy. The SP-free survival and LR/SP-free survival (survival free of both LR and SP) after biochemical failure was estimated with use of the Kaplan-Meier method. Patients with prostate cancer treatment after biochemical failure had their follow-up censored from this study at the time of treatment. Postoperative biochemical failure occurred in 879 men (31%). The mean follow-up from time of biochemical failure was 4.7 years (range, 0.5-11 years). The mean time to biochemical failure was 2.9 years (median, 2.4 years). The overall mean SP-free survival from time of biochemical failure was 94% and 91% at 5 and 10 years, respectively. The mean LR/SP-free survival was 64% and 53% at 5 and 10 years, respectively. By using univariate analysis on the 587 patients with PSADT data, significant risk factors for SP were PSADT (P<.001) and pathologic Gleason score (P=.005); for LR/SP, significant risk factors included PSADT (P<.001) and pathologic Gleason score (P<.001). In multivariate Cox models analysis, only PSADT remained a significant risk factor for both SP and LR/SP (P<.001). Mean 5-year SP-free survival was 99%, 95%, 93%, and 64% for patients with PSADT of 10 years or longer, 1.0 to 9.9 years, 0.5 to 0.9 year, and less than 0.5 year, respectively; the respective mean LR/SP-free survivals were 87%, 62%, 46%, and 38%. The percentage of patients with PSADT of less than 0.5 year was considerably higher if the type of first clinical event was SP (48%) compared with LR (18%) (P<.001). For patients who have undergone radical prostatectomy, a rising PSA level suggests evidence of residual or recurrent prostate cancer. Many men remain free of clinical disease for an extended time after biochemical failure following radical prostatectomy for clinically localized prostate cancer. The PSADT appears to be an important predictor of SP and also of any clinical progression (local or systemic). These data may be useful when counseling men regarding the timing of adjuvant therapies.

DIFFERENCES BETWEEN UROLOGISTS IN THE UNITED STATES AND CANADA IN THE APPROACH TO PROSTATE CANCER

We examine differences in screening, detection, staging and treatment of prostate cancer between urologists in the United States and Canada. An anonymous questionnaire was developed and mailed to 700 randomly selected American and 350 Canadian urologists. The 7 domains of prostate cancer management comprised screening/case identification, radical prostatectomy indications, staging evaluations, neoadjuvant therapy, nerve sparing techniques, postoperative management and treatment of biochemical recurrence. The Dillman method of questionnaire administration was used. All data were stratified by country and analyzed using the generalized chi-square test. Surveys were adequately completed by 45% and 79% of American and Canadian urologists, respectively. Practice experience and clinical volumes were not significantly different between the 2 cohorts. Overall, there were few differences in prostate cancer screening, staging, postoperative management, biochemical failure and use of neoadjuvant therapy. However, practicing American urologists tended to pursue more aggressive case finding practices, such as a higher age cutoff for prostate specific antigen testing (p = 0.0001) and more frequent use of transition zone biopsies (p = 0.0001). American urologists also displayed a tendency toward more liberal indication for extirpative surgery. They were more likely to perform radical prostatectomy in men older than 70 years, those with higher prostate specific antigen and those with node positive disease. Among both national cohorts there was considerable variation in management patterns for all domains of prostate cancer. Variation was most common among treatment of patients with adverse pathological conditions (positive margins, seminal vesicle involvement) and postoperative biochemical failure. Even when credible evidence exists (biopsy technique, preoperative staging) significant proportions of urologists in both countries continued to practice contrary to existing data. American and Canadian practice patterns for prostate cancer differ significantly only in the domains of case identification and surgical indications. In addition, considerable intra-national variation in practice patterns exists. These data highlight the necessity to support randomized clinical trials in prostate cancer.