The 17-gene Onco
DX Genomic Prostate Score (GPS) test predicts adverse pathology (AP) in patients with low-risk prostate cancer treated with immediate surgery. We evaluated the GPS test as a ...predictor of outcomes in a multicenter active surveillance cohort.
Diagnostic biopsy tissue was obtained from men enrolled at 8 sites in the Canary Prostate Active Surveillance Study. The primary endpoint was AP (Gleason Grade Group GG ≥ 3, ≥ pT3a) in men who underwent radical prostatectomy (RP) after initial surveillance. Multivariable regression models for interval-censored data were used to evaluate the association between AP and GPS. Inverse probability of censoring weighting was applied to adjust for informative censoring. Predictiveness curves were used to evaluate how models stratified risk of AP. Association between GPS and time to upgrade on surveillance biopsy was evaluated using Cox proportional hazards models.
GPS results were obtained for 432 men (median follow-up, 4.6 years); 101 underwent RP after a median 2.1 years of surveillance, and 52 had AP. A total of 167 men (39%) upgraded at a subsequent biopsy. GPS was significantly associated with AP when adjusted for diagnostic GG (hazards ratio HR/5 GPS units, 1.18; 95% CI, 1.04 to 1.44;
= .030), but not when also adjusted for prostate-specific antigen density (PSAD; HR, 1.85; 95% CI, 0.99 to 4.19;
= .066). Models containing PSAD and GG, or PSAD, GG, and GPS may stratify risk better than a model with GPS and GG. No association was observed between GPS and subsequent biopsy upgrade (
= .48).
In our study, the independent association of GPS with AP after initial active surveillance was not statistically significant, and there was no association with upgrading in surveillance biopsy. Adding GPS to a model containing PSAD and diagnostic GG did not significantly improve stratification of risk for AP over the clinical variables alone.
For men on active surveillance for prostate cancer, utility of prostate-specific antigen (PSA) kinetics (PSAk) in predicting pathologic reclassification remains controversial.
To develop prediction ...methods for utilizing serial PSA and evaluate frequency of collection.
Data were collected from men enrolled in the multicenter Canary Prostate Active Surveillance Study, for whom PSA data were measured and biopsies performed on prespecified schedules. We developed a PSAk parameter based on a linear mixed-effect model (LMEM) that accounted for serial PSA levels.
The association of diagnostic PSA and/or PSAk with time to reclassification (increase in cancer grade and/or volume) was evaluated using multivariable Cox proportional hazards models.
A total of 851 men met the study criteria; 255 (30%) had a reclassification event within 5 yr. Median follow-up was 3.7 yr. After adjusting for prostate size, time since diagnosis, biopsy parameters, and diagnostic PSA, PSAk was a significant predictor of reclassification (hazard ratio for each 0.10 increase in PSAk=1.6 95% confidence interval 1.2–2.1, p<0.001). The PSAk model improved stratification of risk prediction for the top and bottom deciles of risk over a model without PSAk. Model performance was essentially identical using PSA data measured every 6 mo to those measured every 3 mo. The major limitation is the reliability of reclassification as an end point, although it drives most treatment decisions.
PSAk calculated using an LMEM statistically significantly predicts biopsy reclassification. Models that use repeat PSA measurements outperform a model incorporating only diagnostic PSA. Model performance is similar using PSA assessed every 3 or 6 mo. If validated, these results should inform optimal incorporation of PSA trends into active surveillance protocols and risk calculators.
In this report, we looked at whether repeat prostate-specific antigen (PSA) measurements, or PSA kinetics, improve prediction of biopsy outcomes in men using active surveillance to manage localized prostate cancer. We found that in a large multicenter active surveillance cohort, PSA kinetics improves the prediction of surveillance biopsy outcome.
In this report, we looked at whether repeat prostate-specific antigen (PSA) measurements, or PSA kinetics, improve prediction of biopsy outcomes in men using active surveillance to manage localized prostate cancer. We found that in a large multicenter active surveillance cohort, PSA kinetics improves the prediction of surveillance biopsy outcome.
Purpose Positive surgical margins are an independent predictive factor for biochemical recurrence after radical prostatectomy. We analyzed the incidence of and associative factors for positive ...surgical margins in a multi-institutional series of 8,418 robotic assisted radical prostatectomies. Materials and Methods We analyzed the records of 8,418 patients who underwent robotic assisted radical prostatectomy at 7 institutions. Of the patients 323 had missing data on margin status. Positive surgical margins were categorized into 4 groups, including apex, bladder neck, posterolateral and multifocal. The records of 6,169 patients were available for multivariate analysis. The variables entered into the logistic regression models were age, body mass index, preoperative prostate specific antigen, biopsy Gleason score, prostate weight and pathological stage. A second model was built to identify predictive factors for positive surgical margins in the subset of patients with organ confined disease (pT2). Results The overall positive surgical margin rate was 15.7% (1,272 of 8,095 patients). The positive surgical margin rate for pT2 and pT3 disease was 9.45% and 37.2%, respectively. On multivariate analysis pathological stage (pT2 vs pT3 OR 4.588, p <0.001) and preoperative prostate specific antigen (4 or less vs greater than 10 ng/ml OR 2.918, p <0.001) were the most important independent predictive factors for positive surgical margins after robotic assisted radical prostatectomy. Increasing prostate weight was associated with a lower risk of positive surgical margins after robotic assisted radical prostatectomy (OR 0.984, p <0.001) and a higher body mass index was associated with a higher risk of positive surgical margins (OR 1.032, p <0.001). For organ confined disease preoperative prostate specific antigen was the most important factor that independently correlated with positive surgical margins (4 or less vs greater than 10 ng/ml OR 3.8, p <0.001). Conclusions The prostatic apex followed by a posterolateral site was the most common location of positive surgical margins after robotic assisted radical prostatectomy. Factors that correlated with cancer aggressiveness, such as pathological stage and preoperative prostate specific antigen, were the most important factors independently associated with an increased risk of positive surgical margins after robotic assisted radical prostatectomy.
Introduction
Since sipuleucel-T approval in 2010, the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) now includes the androgen-receptor signaling pathway inhibitors ...(ASPIs) abiraterone acetate or enzalutamide. In 2013 and 2014, these oral agents were approved for use in men with metastatic prostate cancer who had minimal to no symptoms. We compared overall survival (OS) in men who received their first mCRPC treatment using the Medicare Fee-for-Service 100% administrative claims research dataset with patient-level linkage to the National Death Index.
Methods
This retrospective cohort analysis (January 2013 to December 2017) included men who were chemo-naïve at treatment start in 2014 and who had continuous Medicare Parts A, B, and D eligibility during the 3-year observation period. We compared: first-line sipuleucel-T vs. first-line ASPIs and any-line sipuleucel-T vs. any-line ASPIs (without sipuleucel-T). We used a multivariable regression model to help control for potentially confounding factors while assessing survival outcomes.
Results
The model included 6044 eligible men (average age 75–78 years) with similar disease severity; > 80% were white. Median OS, presented as sipuleucel-T vs. ASPI, was 35.2 vs. 20.7 months (
n
, 906 vs. 5092; any-line cohort) and 34.9 vs. 21.0 months (
n
, 647 vs. 4810; first-line cohort). Model outcomes indicated sipuleucel-T was associated with significantly prolonged OS compared with ASPIs: adjusted hazard ratio, 0.59 (95% CI 0.527–0.651) and 0.56 (0.494–0.627) for the any-line and first-line cohorts, respectively.
Conclusion
This analysis suggests use of sipuleucel-T at any time was associated with improved OS compared with ASPI use alone. Of note, these analyses are intended as descriptive rather than definitive as this dataset contains limited data on key clinical factors. While selection bias is a risk in secondary claims data, this research provides important insight into real-world treatment outcomes.
For men on active surveillance for prostate cancer, biomarkers may improve prediction of reclassification to higher grade or volume cancer. This study examined the association of urinary PCA3 and ...TMPRSS2:ERG (T2:ERG) with biopsy-based reclassification.
Urine was collected at baseline, 6, 12, and 24 months in the multi-institutional Canary Prostate Active Surveillance Study (PASS), and PCA3 and T2:ERG levels were quantitated. Reclassification was an increase in Gleason score or ratio of biopsy cores with cancer to ≥34%. The association of biomarker scores, adjusted for common clinical variables, with short- and long-term reclassification was evaluated. Discriminatory capacity of models with clinical variables alone or with biomarkers was assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA).
Seven hundred and eighty-two men contributed 2069 urine specimens. After adjusting for PSA, prostate size, and ratio of biopsy cores with cancer, PCA3 but not T2:ERG was associated with short-term reclassification at the first surveillance biopsy (OR = 1.3; 95% CI 1.0-1.7, p = 0.02). The addition of PCA3 to a model with clinical variables improved area under the curve from 0.743 to 0.753 and increased net benefit minimally. After adjusting for clinical variables, neither marker nor marker kinetics was associated with time to reclassification in subsequent biopsies.
PCA3 but not T2:ERG was associated with cancer reclassification in the first surveillance biopsy but has negligible improvement over clinical variables alone in ROC or DCA analyses. Neither marker was associated with reclassification in subsequent biopsies.
Laparoscopic radical prostatectomy is being evaluated at several centers in the United States as a treatment option for localized prostate cancer. It is a technically difficult operation to perform ...with a steep learning curve. It has been stated that 50 procedures are necessary to satisfy the learning curve. To expedite performance and evaluation of laparoscopic radical prostatectomy a surgeon (mentor) who had performed 200 cases was invited to instruct a fellowship trained laparoscopist (trainee).
From March 2001 through September 2001 we performed 30 laparoscopic radical prostatectomies. The mentor performed the first 12 procedures with the trainee acting as assistant (group 1). The subsequent 18 procedures were performed by the trainee with the mentor acting as assistant (group 2). A final set of 20 procedures was performed by the trainee alone using 1 of 3 urological residents as the assistant (group 3). The transperitoneal approach was used and all suturing was intracorporeal. Preoperative data included prostate specific antigen, clinical stage, Gleason grade and median patient age. Intraoperative data included operative time, the blood loss/transfusion rate and intraoperative complications. Postoperative data included pathological stage, prostate specific antigen, the positive margin rate, catheter dwell time and hospital stay. When applicable, statistical significance was determined using the standard paired t test.
There was no statistical difference in median operative time in groups 1 and 2 (248 and 258 minutes, respectively, p = 0.15). Similarly there was no difference in groups 2 (trainee and mentor assistant) and 3 (trainee alone) (p = 0.26). There was a difference in operative time in groups 1 and 3 (p = 0.04). Mean estimated blood loss was comparable in groups 1 to 3 and not statistically different (150, 250 and 250 cc, respectively, p = 0.15). Mean organ weight was also comparable (64, 59 and 55 gm., respectively). Hospital stay was 3 days in all groups. Catheter time decreased as confidence was gained with the procedure (range 6 to 33 days). Final pathological stage was compared among the 3 groups. There was an overall increase in positive margins in groups 1 to 3 (16%, 22% and 30%, respectively, p not significant). However, the positive margin rate for stage pT2 disease was similar at 15.5% for groups 1 and 2, and 14% for group 3.
Laparoscopic radical prostatectomy is a technically challenging operation that is in the early stages of evolution and evaluation. We present an intensive, mentor initiated approach to decrease the learning curve and maintain outcomes.
There is a paucity of prospective long-term data on living kidney donor (LKD) quality of life (QoL). The Living Organ Donor Network (LODN) database follows donors longitudinally and cross-references ...with United Network for Organ Sharing (UNOS) data to assess factors that affect donor QoL.
The Short Form (SF)-36 was sent to donors at 6 months and yearly thereafter. Recipient outcomes were determined from the UNOS database. Of 2219 donors, 1030 returned ≥ 1 QoL survey in the first year. Seven-hundred and thirty-one donors returned at least two surveys with 51 associated with a nonfunctioning graft and 38 with recipient death.
Initial QoL scores were not different between donors whose recipients were alive with graft function, and those whose recipients died (88.9 vs 89.2, P = 0.87). For donors whose recipient died, QoL in the year after recipient death averaged 6 points lower than the initial QoL (88.9 vs 82.9, P = 0.01). Thirty-one donors returned surveys an average of 4.1 years after their recipient's death. Final QoL score increased by 2.5 points, no longer significantly lower than the initial QoL (85.4 vs 88.9, P = 0.16). Thirty-eight donors returned surveys in the year after their recipient's graft failure and their QoL decreased by 5.6 points on average (86.9 vs 81.2, P = 0.07). Twenty-eight of these donors returned future surveys and final QoL was unchanged (81.2 vs 81.2, P = 0.99).
Donor QoL declines after recipient death but recovers with time. Graft failure resulted in decreased QoL without recovery. The LODN database identifies factors affecting LKD QoL and provides a model for a national registry.
Reapproximation of Denonvilliers' fascia adjacent to bladder neck to the rectourethralis, or posterior reconstruction (PR), has been suggested to improve continence in postprostatectomy patients. We ...examined the impact of the PR on postoperative urinary and other quality-of-life (QoL) outcomes in patients undergoing robot-assisted laparoscopic prostatectomy (RALP).
We identified 89 patients who underwent RALP for prostate cancer between 2006 and 2009 by a single surgeon (R.G.), consented to participate in our prospective QoL study, which collects RAND-UCLA QoL and AUA symptom scores for all patients undergoing treatment for prostate cancer, and completed a baseline and a 3- or 6-month questionnaire. Of these, 31 patients had PR before vesicourethral anastomosis. We compared return to baseline function percentage at 3 and 6 months by PR group. Differences found in univariate analysis were further investigated using multiple linear regression models adjusting for demographics, clinical variables, and nerve-sparing status.
While most patients had both 3- and 6-month follow-up (n = 74, 83%), sample size at 3 months was n = 86 and at 6 months was n = 77. Groups were comparable by preoperative characteristics, pathologic stage, nerve-sparing status, and baseline QoL/AUA symptom scores. At 3-months, there was a statistically significant improvement comparing PR to non-PR groups in return to baseline score for urinary bother (72% vs. 53%; p = 0.008) and urinary function (64% vs. 50%; p = 0.05), as well as change in absolute AUA symptom score (+0.2 vs. +3.8; p = 0.005). Differences in urinary bother (+20%; 95% confidence interval 5%, 34%) and AUA symptom score (-2.8; 95% confidence interval, -5.4, -0.2) persisted after multivariate adjustment. Groups had similar scores for all parameters by 6 months postprostatectomy.
PR in patients undergoing RALP has a significant impact on early return to baseline parameters relating to urinary bother, urinary function, and AUA symptom score.
Objective:
Herein we report our experience of 49 consecutive pyeloplasties that were all laparoscopically performed with an intracorporeally sutured anastomosis. We describe the operative technique, ...complications and outcomes during a follow-up period of 1–53 months (mean 23.2 months).
Patients and Methods:
Forty-nine patients (28 women and 21 men) with a mean age of 34 years (range 6–65 years) underwent a laparoscopic dismembered pyeloplasty because of primary ureteropelvic junction (UPJ) obstruction with hydronephrosis in each case. The preoperative evaluation included an evaluation for pain, an excretory urography (IVP), renal scan and sometimes CT angiography to evaluate for crossing vessels. Follow-up studies included an IVP, renal scan and renal ultrasound 4 weeks postoperatively and every 3 months thereafter. Success was considered as improvement of the pain score and IVP (less hydronephrosis, visible UPJ and/or normalization of drainage) or absence of an obstructive pattern during the washout phase of a renal scan.
Results:
There was no conversion to open surgery. The mean operative time was 165
min (range 90–240
min). Blood loss was negligible. Crossing vessels were noted in 57.1% of the patients (28/49). Postoperative hospital stay was 3.7 days (range 3–6 days). One patient had a leakage of the anastomosis on postoperative day 1 and needed to undergo laparoscopic repair. The mean follow-up is 23.2 months (range 1–53 months). There was one single late failure. This patient later underwent an open revision of the laparoscopic pyeloplasty. In all other patients (48/49), the obstruction was resolved or significantly improved. The long-term success rate is 97.7%.
Conclusions:
The results of dismembered laparoscopic pyeloplasties compare favorably with those achieved by open pyeloplasties with less perioperative morbidity and discomfort. We do believe that laparoscopic dismembered pyeloplasty with an intracorporeal anastomosis is the method of choice in the treatment of the UPJ obstruction in the presence of an enlarged renal pelvis and crossing vessels.
While partial nephrectomy remains the gold standard for the management of most small renal masses, increasing experience with renal cryoablation has suggested a viable alternative with a favorable ...morbidity profile and good efficacy. We report intermediate-term oncologic outcomes from a single-center experience with laparoscopic and percutaneous renal cryoablation.
We performed a retrospective review of our laparoscopic renal cryoablation (LRC) and percutaneous renal cryoablation (PRC) experience between January 2003 and April 2007. Patients with at least 12 months of follow-up were included in the analysis. Follow-up consisted of imaging and laboratory studies at regular intervals. Persistent mass enhancement or interval tumor growth was considered a treatment failure.
Sixty-six patients (44% women/56% men; 42% African-American/58% Caucasian/other; mean body mass index, 29.7) with 72 tumors underwent either LRC (n = 52) or PRC (n = 20) with a mean follow-up of 30 months (median 25.1 mos; range 13-63 mos). Average patient age was 66.5 years (range 34-82 yrs). Mean tumor size was 2.33 cm (range 1-4.6 cm). Comorbid conditions were prevalent: 76% hypertension, 36% hyperlipidemia, 24% chronic kidney disease, 29% diabetes mellitus, 36% tobacco use, and 32% heart disease. RESULTS of pretreatment biopsy were 62% renal-cell carcinoma and 38% benign or nondiagnostic. Overall cancer-specific and cancer-free survival were 100% and 97%, respectively. There were two treatment failures (3.8%) in the LRC group and five primary failures in the PRC group (25%) (P = 0.015), four of which were salvaged with repeated PRC with no evidence of recurrence at 6 to 36 months of follow-up. There has been no significant local or metastatic progression.
LRC and PRC achieved good oncologic control with minimal morbidity at a mean follow-up of 30 months in a patient cohort characterized by numerous comorbid conditions. PRC had a significantly higher primary treatment failure rate than LRC, but re-treatment offered salvage oncologic control with no significant complications.
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