Effect of stone composition on surgical stone recurrence: single center longitudinal analysis.

INTRODUCTION The objective of this study is to explore the association between urinary stone composition and surgical recurrence. MATERIALS AND METHODS: Patients who underwent kidney stone surgeries (between 2009-2017), were followed for > 1 year, and had ≥ 1 stone composition analyses were included in our analysis. Surgical stone recurrence (repeat surgery) was defined as the second surgery on the same kidney unit. Recurrence-free survival analysis was used. RESULTS: A total number of 1051 patients were included (52.7% men, average age 59.1 +/- 15.1 years). Over 4.7 +/- 2.5 years follow up, 26.7% of patients required repeat surgery. Patients' stone compositions were calcium oxalate (66.0%), uric acid (12.2%), struvite (10.0%), brushite (5.7%), apatite (5.1%) and cystine (1.0%). Results suggested that patients with cystine stones had the highest surgical recurrence risk; brushite had the second-highest surgical recurrence risk. Struvite, uric acid, and apatite stones were at higher risk compared with calcium oxalate stones (lowest risk in our cohort). When pre and postoperative stone size was controlled, patients with a history of uric acid, brushite, and cystine stones were at higher surgical risk. After controlling clinical and demographic factors, only brushite and cystine stones were associated with higher surgical recurrence. CONCLUSIONS: Patients with cystine stones had the highest surgical recurrence risk; brushite stones had the second highest surgical recurrence risk. Struvite, uric acid, and apatite stones were at higher risk compared with calcium oxalate stones. When pre and postoperative stone size, clinical and demographic factors were controlled, only those with brushite or cystine stones were at significantly higher risk of surgical recurrence.

Gender-related differences in the risk factors for repeat stone surgery.

Our objective was to analyze and compare the associations between potential risk factors for nephrolithiasis and repeat stone surgery in male and female patients. We retrospectively analyzed 1970 patients who had stone surgery at our institution in the period from January 2009 to May 2017, were older than 18 years and had at least 12 months of postoperative follow-up. Our definition of surgical recurrence included repeat surgery on the same renal unit or on the opposite renal unit if the original imaging did not demonstrate significant stones on that side. Uni- and multivariate Cox regression models were built for each gender. We also explored the interactions between gender and other patient's characteristics in their effect on the risk of recurrence. Ureteroscopy was the most common treatment modality for both first (83%) and repeat (87%) procedures. Over a mean follow-up of 4.3 years (median 3.8, interquartile range 2.2-6.0), 413 (21.0%) patients had a surgical recurrence. In multivariate analyses, hypertension, diabetes, Caucasian race and younger age (less than 60 years) were significantly associated with the risk of surgical recurrence only in females. Interaction between these characteristics and gender was significant indicating a larger effect on the risk of surgical recurrence in females compared to males. Our study demonstrated a number of differences in the predictors of repeat surgery for nephrolithiasis between males and females. If confirmed by future studies these differences may be helpful for optimizing nephrolithiasis prevention efforts.

Development and validation a task-specific checklist for a microsurgical varicocelectomy simulation model

ABSTRACT Purpose: To develop and validate a new test of specific technical skills required for microsurgical varicocelectomy. Materials and Methods: An electronic questionnaire was sent to 558 members of the Brazilian Society of Urology for the validation of the task-specific checklist (TSC) for assessment of microsurgical varicocelectomy. Participants who had experience in this procedure were selected as judges. For construct validation, 12 participants including attending urologists and urological residents in training were recruited for voluntary participation. We formed a group of three experts and a group of nine novices, who had to perform the steps of microsurgical varicocelectomy on a simulation model using human placenta. Each participant was filmed and two blinded raters would then evaluate their performance using the TSC of microsurgical varicocelectomy. Results: 14 judges were recruited. The assessment tool was reformulated, according to the judges suggestions and had the content validity achieved. The final version of the TSC was comprised of the task-specific score, a series of 4 items scored in a binary fashion designed for microscopic sub-inguinal varicocelectomy. The differences between the performance of participants with different levels of experience reflected the construct validity. The reliability between the raters was high. The mean time required to complete the training of microsurgical varicocelectomy in simulation model was significantly shorter for experts compared to novices (201 vs. 496 seconds, p=0.01). Conclusions: This preliminary study suggests that the task-specific checklist of microsurgical varicocelectomy is reliable and valid in assessing microsurgical skills.

Development and validation a task-specific checklist for a microsurgical varicocelectomy simulation model.

PURPOSE: To develop and validate a new test of specific technical skills required for microsurgical varicocelectomy. MATERIALS AND METHODS: An electronic questionnaire was sent to 558 members of the Brazilian Society of Urology for the validation of the task-specific checklist (TSC) for assessment of microsurgical varicocelectomy. Participants who had experience in this procedure were selected as judges. For construct validation, 12 participants including attending urologists and urological residents in training were recruited for voluntary participation. We formed a group of three experts and a group of nine novices, who had to perform the steps of microsurgical varicocelectomy on a simulation model using human placenta. Each participant was filmed and two blinded raters would then evaluate their performance using the TSC of microsurgical varicocelectomy. RESULTS: 14 judges were recruited. The assessment tool was reformulated, according to the judges suggestions and had the content validity achieved. The final version of the TSC was comprised of the task-specific score, a series of 4 items scored in a binary fashion designed for microscopic sub-inguinal varicocelectomy. The differences between the performance of participants with different levels of experience reflected the construct validity. The reliability between the raters was high. The mean time required to complete the training of microsurgical varicocelectomy in simulation model was significantly shorter for experts compared to novices (201 vs. 496 seconds, p=0.01). CONCLUSIONS: This preliminary study suggests that the task-specific checklist of microsurgical varicocelectomy is reliable and valid in assessing microsurgical skills.

Influence of Lower Pole Infundibulopelvic Angle on Success of Retrograde Flexible Ureteroscopy and Laser Lithotripsy for the Treatment of Renal Stones.

Objectives: Influence of renal anatomy on success rates for shockwave lithotripsy has been reported in the literature with emphasis on lower pole anatomy. Influence of renal anatomy has not been evaluated in the setting of ureteroscopy and laser lithotripsy for stone treatment. This study analyzed the influence of infundibulopelvic angle (IPA) of the lower pole on the outcomes of ureteroscopy and laser lithotripsy with respect to stone-free rate and surgical recurrence. Materials and Methods: We retrospectively analyzed 735 renal units undergoing retrograde flexible ureteroscopy (fURS) with laser lithotripsy between January 2009 and December 2016. All cases were performed at a single institution. No exclusion criterion was applied with regard to preoperative stone location. Success was defined as no evidence of residual stone fragments on kidney, ureter, and bladder radiograph within 2 months of surgery. Failure was defined as any stone present on imaging. Lower pole IPA was measured on intraoperative retrograde pyelogram as described by Elbahanasy et al. Univariate and multivariate analyses of factors contributing to stone-free rate were performed. Secondary outcomes included surgical recurrence-free survival. Results: Of the 735 cases evaluated, 243 cases had a retrograde pyelogram stored in our Picture Archiving and Communication System (PACS) sufficient for IPA interpretation. Of these patients, 122 (50%) were women. In total, 127 patients (52.3%) were stone free on follow-up imaging, whereas 116 (47.7%) had residual stone burden. In total, 144 (59%) patients had ≤3 mm stone burden on follow-up imaging. In multivariate analysis, residual stone fragments were significantly associated with acute IPA <90° (<0.001), lower pole stones preoperatively (<0.001), and larger stone size (0.001). IPA <90° and larger stone size were both found to be statistically significantly associated with need for repeat surgery. Conclusions: Our data show that more acute IPA and larger preoperative stone size negatively affect stone-free rate and need for repeat surgery after retrograde fURS with laser lithotripsy for treatment of renal stones.

Clinical and demographic predictors of repeat stone surgery.

OBJECTIVE: To identify the clinical and demographic predictors of repeat stone surgery. MATERIALS AND METHODS: We retrospectively analysed 1496 consecutive patients, aged > 18 years, who underwent stone surgery at our institution in the period from January 2009 to May 2017 and who had at least 12 months of postoperative follow-up. We defined surgical recurrence as repeat surgery on the same renal unit or on the opposite renal unit if the original imaging did not demonstrate significant stones on that side. Characteristics associated with the risk of surgical recurrence in univariate Cox regression analysis were entered into a multivariate model. RESULTS: Most patients underwent ureteroscopy and laser lithotripsy (83.0%). Approximately 60% of the patients had a personal history of stone disease and 50% were obese. Over a mean (median; interquartile range) follow-up of 4.1  (3.9; 2.4-5.9) years, 24.5% of patients had surgical recurrence, with 82% of repeat surgeries performed for symptomatic nephrolithiasis. The factors associated with increased risk of surgical recurrence in the multivariate model were: age <60 years, female gender, malabsorptive gastrointestinal disease, diabetes, recurrent urinary tract infections, personal history of nephrolithiasis, renal stones and bilateral nephrolithiasis. The hazard ratios for these variables ranged within an interval of <0.5 (from 1.30 to 1.71). CONCLUSION: We identified eight demographic and clinical factors associated with increased risk of repeat renal stone surgery. These factors could be combined as a numerical count that allows stratification of patients into low-, intermediate- and high-risk subgroups.

External Validation of the Recurrence of Kidney Stone Nomogram in a Surgical Cohort.

Objective: To assess the performance of recurrence of kidney stone (ROKS) nomogram in identifying first-time stone formers who will require future stone procedures. Materials and Methods: From January 2009 to February 2016, 2287 patients underwent surgical treatment for nephrolithiasis at our institution and 498 of them were eligible for this study. We defined recurrence as repeat surgery for symptomatic nephrolithiasis. We analyzed the performance of the nomogram with respect to discrimination, calibration, and the clinical net benefit. We also examined the performance of each individual variable from the nomogram. Results: Over a median follow-up of 4.8 years (mean 4.6, IQR 3.1-6.1), 88 patients (17.7%) had recurrent nephrolithiasis requiring surgical treatment. The ROKS nomogram demonstrated moderate discriminative ability (AUC 0.655 for 2 years and 0.605 for 5 years). Calibration of the ROKS nomogram-based predictions was poor and net clinical benefit was minimal. Three of 11 predictors from the nomogram were statistically significantly associated with the risk of repeat surgery, with two of them representing similar clinical scenarios, namely symptomatic and nonsymptomatic renal stones. Conclusion: ROKS nomogram demonstrated limited discrimination and calibration in predicting the risk of repeat surgery for symptomatic nephrolithiasis in our cohort of first-time stone formers. This may be caused by the differences between stone patients who do and do not require surgery and suggests the need for development of more precise prediction instruments.

Role of Residual Fragments on the Risk of Repeat Surgery after Flexible Ureteroscopy and Laser Lithotripsy: Single Center Study.

PURPOSE: We analyzed the impact of residual stone fragments seen on abdominal x-ray after ureteroscopy and laser lithotripsy on the risk of repeat surgical intervention. MATERIALS AND METHODS: Our study included 781 patients (802 renal units) who underwent ureteroscopy and laser lithotripsy with abdominal x-ray within 3 months postoperatively and who had at least 1 year of followup. Ureteroscopy and laser lithotripsy were performed using the dusting technique. We analyzed the association between surgical recurrence-free survival and the size of the largest residual fragment. RESULTS: During a median followup of 4.2 years repeat surgery was performed on 161 renal units (20%). Of the repeat interventions 75% were done for symptomatic nephrolithiasis. Postoperative imaging showed residual stone fragments in 42% of cases. In the entire group the risk of repeat surgery was increased in renal units with residual fragments greater than 2 mm. The effect of the size of residual fragments on the risk of surgical recurrence varied by patient body mass index. It was much larger in nonobese subjects, who were at increased risk for repeat surgery with residual fragments of any size. In the obese subgroup only fragments greater than 2 mm increased the risk of surgical recurrence. CONCLUSIONS: The association between the size of residual stone fragments detected by abdominal x-ray after ureteroscopy and laser lithotripsy, and the risk of repeat surgical intervention depends on patient body mass index. Nonobese patients with residual stone fragments of any size are at increased risk for repeat intervention compared to those with a negative abdominal x-ray. The predictive value of abdominal x-ray after ureteroscopy and laser lithotripsy is limited in obese patients.

A Comprehensive Analysis of the Association Between Gleason Score at a Positive Surgical Margin and the Risk of Biochemical Recurrence After Radical Prostatectomy.

Our objective was to identify the best of the existing definitions of Gleason score (GS) at a positive surgical margin (PSM) by validating them in our radical prostatectomy cohort. We analyzed 251 patients who had mixed (3+4, 3+5, 4+3 or 5+3) pathologic GS and PSM. We used 5 definitions to record GS at a PSM. Univariate and multivariate analyses were used to study the association between each definition and the risk of biochemical recurrence (BCR). We also tested the prognostic value of multivariate models including established predictors and each of the studied definitions of GS at a PSM. GS 3+3 was seen at a PSM in 57.4% of the cases and was more common in patients with lower overall GS. Over a median follow-up of 4.0 years 89 patients (35.5%) developed BCR. All of the definitions of GS at a PSM were independent predictors of the BCR-free survival. Most of them also improved the prognostic value of the multivariate models when added to the established parameters. The degree of improvement was similar for the most complex definition (full GS at a PSM) and the easiest to record binary definition (presence of Gleason 4/5 pattern at a PSM). We conclude that compared with the other possible options of reporting GS at a PSM, the presence of Gleason 4/5 pattern may be the most practical definition. It is at least as predictive as other definitions, may be the easiest to record and is the best studied of the existing alternatives.

Predictive models and risk of biopsy progression in active surveillance patients.

OBJECTIVE: To analyze the performance of different radical prostatectomy-based prognostic tools in predicting the biopsy progression in our active surveillance cohort. MATERIALS AND METHODS: We analyzed 326 patients with biopsy Gleason grade≤6,≤2 positive biopsy cores,≤20% tumor present in any core, prostate-specific antigen<15ng/dl, and clinical stages T1-T2a all of whom had at least single surveillance biopsy. Probabilities of pathologically relatively aggressive disease were estimated using Partin and Dinh risk tables and Kattan, Truong, and Kulkarni nomograms for each individual patient. Using these predictions, performance of these tools was quantified regarding discrimination, stratification at different cut-points, calibration, and the clinical net benefit. RESULTS: Predictions of Partin and Dinh tables were not associated with the biopsy progression. The predictive value of Kattan and Truong nomograms was higher when compared with the other tools, although it was significant only on the first and second surveillance biopsies. Both nomograms were able to identify low- and high-risk subgroups within the cohort. Kattan nomogram demonstrated better correlation with the observed rate of progression over the first 3 biopsies and higher clinical net benefit. CONCLUSION: Kattan and Truong nomograms demonstrated the best performance in predicting biopsy progression, although their value was largely limited to the first 2 surveillance biopsies. Both tools were able to stratify patients into subgroups with different risks of progression. These nomograms have important differences, which suggest that a more effective predictive model combining the strong sides of both tools and possibly some other variables could be developed.

Is It Time to Revisit the Role of Prostate-specific Antigen Kinetics in Active Surveillance for Prostate Cancer?

OBJECTIVE: To identify factors that are not available at the time of prostate cancer diagnosis and are associated with the risk of biopsy progression in active surveillance (AS) patients. MATERIALS AND METHODS: The study included 314 AS patients who had at least 1 repeat biopsy. We used logistic regression to analyze the association between prostate-specific antigen (PSA) and its derivatives, including PSA density, PSA velocity (PSAV) and doubling time (PSADT); presence of bilateral disease and number of previous successive negative surveillance biopsies; and the risk of progression on the surveillance biopsies first through fourth. RESULTS: Over a median follow-up of 3.1 years, patients had a mean of 2.4 biopsies. The median time from diagnosis to the last biopsy was 2.3 years. The biopsies were performed at fairly equal intervals. For surveillance biopsies 1 through 3, none of the studied factors was adding significant prognostic information to the baseline characteristics. PSAV and PSADT were associated with the risk of progression on the fourth biopsy; this association was independent of baseline characteristics. No progression on the fourth biopsy was noted in 23 patients with negative PSAV. Among 54 patients with PSADT of more than 3 years only, 2 progressed whereas 6 out of 9 patients with a PSADT less than 3 years had biopsy progression on the fourth surveillance biopsy. CONCLUSION: PSA kinetics may be helpful in defining the indications for prostate biopsy in AS patients who are followed with regular biopsies for more than 3-4 years.

Prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in active surveillance patients.

OBJECTIVE: To analyze the association between prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in prostate cancer patients on active surveillance, and to study the effect of prediagnostic prostate-specific antigen values on the predictive performance of prostate-specific antigen velocity and prostate-specific antigen doubling time. METHODS: The study included 137 active surveillance patients with two or more prediagnostic prostate-specific antigen levels measured over a period of at least 3 months. Two sets of analyses were carried out. First, the association between prostate-specific antigen kinetics calculated using only the prediagnostic prostate-specific antigen values and the risk of biopsy progression was studied. Second, using the same cohort of patients, the predictive value of prostate-specific antigen kinetics calculated using only post-diagnostic prostate-specific antigens and compared with that of prostate-specific antigen kinetics based on both pre- and post-diagnostic prostate-specific antigen levels was analyzed. RESULTS: Of 137 patients included in the analysis, 37 (27%) had biopsy progression over a median follow-up period of 3.2 years. Prediagnostic prostate-specific antigen velocity of more than 2 ng/mL/year and 3 ng/mL/year was statistically significantly associated with the risk of future biopsy progression. However, after adjustment for baseline prostate-specific antigen density, these associations were no longer significant. None of the tested prostate-specific antigen kinetics based on combined pre- and post-diagnostic prostate-specific antigen values were statistically significantly associated with the risk of biopsy progression. CONCLUSIONS: Historical prediagnostic prostate-specific antigens seems to be not clinically useful in patients diagnosed with low-risk prostate cancer on active surveillance.

Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer.

BACKGROUND: Many patients with low-risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low-risk PC. METHODS: More than 30 clinicopathologic parameters were assessed in consecutive patients with Gleason 6 PC upon biopsy who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason ≥ 7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in 2 separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision analysis. RESULTS: On multivariable analysis, variables predicting upgrading were prostate-specific antigen density using ultrasound (odds ratio [OR] = 229, P = .003), obesity (OR = 1.90, P = .05), number of positive cores (OR = 1.23, P = .01), and maximum core involvement (OR = 0.02, P = .01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all 3 cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated areas under the curve of 0.597 to 0.672 for predicting upgrading in subsets of men with very low-risk PC who meet active surveillance criteria (all P < .001), allowing further risk stratification of these individuals. CONCLUSIONS: A nomogram was developed and externally validated that uses preoperative clinical parameters and biopsy findings to predict the risk of pathological upgrading in Gleason 6 patients. This can be used to further inform patients with lower risk PC who are considering treatment or active surveillance.

Improving risk stratification in patients with prostate cancer managed by active surveillance: a nomogram predicting the risk of biopsy progression.

OBJECTIVE: To develop a clinical tool that integrates different risk factors and provides individual predictions of the risk of biopsy progression in patients with prostate cancer managed by active surveillance. MATERIALS AND METHODS: Our analysis included 205 patients on active surveillance, each of whom had had at least two surveillance biopsies. We used the Cox proportional hazard regression model to analyse the association between different risk factors and progression-free survival over successive biopsies. This multivariate model was then used to develop a nomogram. Discrimination and calibration of the nomogram were internally validated using 200 bootstrap resamplings. RESULTS: The median follow-up of patients free of progression was 4.6 years. A total of 58 (28%) patients experienced progression. Factors significantly associated with progression were: overall number of positive cores in the diagnostic and first surveillance biopsies, race and prostate-specific antigen density. The bootstrapping concordance index of the nomogram including these variables was 81%. The nomogram tended to underestimate the probability of progression but it identified fairly accurately the distinct groups of patients at low, intermediate and high risk of progression. CONCLUSIONS: In the development cohort, the nomogram was able to separate patients with respect to their risk of biopsy progression. Since accurate risk stratification is essential to optimize patient care, this tool, if external validation confirms its performance, may prove useful for both the counselling and management of patients with low-volume, Gleason 6 prostate cancer.

Comparative validation of nomograms predicting clinically insignificant prostate cancer.

OBJECTIVE: To validate and compare the accuracy and performance of nomograms predicting insignificant prostate cancer and to analyze their performance in patients with different cancer locations. METHODS: Our cohort consisted of 370 radical prostatectomy patients with Gleason ≤6 prostate cancer diagnosed on transrectal biopsy with at least 10 cores. We quantified the performance of each nomogram with respect to discrimination, calibration, predictive accuracy at different cut points, and the clinical net benefit. We also evaluated these parameters in subgroups of patients with predominantly anterior-apical (AA) and posterior-basal (PB) tumor location. RESULTS: Insignificant prostate cancer was present in 141 patients (38%). The Kattan and Steyerberg nomograms outperformed other studied models and demonstrated fair discrimination (areas under the receiver operating characteristics curve 0.768 and 0.770, respectively), good calibration, balanced predictive accuracy, and the highest net benefit. All nomograms were less accurate at higher levels of predicted probability. The performance of the nomograms was better in patients with PB tumors than in those with AA tumors. The loss of correlation with the actual prevalence of insignificant prostate cancer at higher levels of predicted probability was not seen in the PB subgroup but was particularly noticeable in the AA subgroup. CONCLUSION: The Kattan and Steyerberg nomograms demonstrated the best performance in predicting the probability of insignificant prostate cancer in a contemporary cohort of patients with Gleason ≤6 cancer diagnosed on specimens from an extended transrectal biopsy. However, all studied nomograms were more accurate in identifying significant rather than insignificant disease, particularly for tumors located in the apical and anterior prostate.

Renal volumetric analysis: a new paradigm in renal mass treatment assessment.

UNLABELLED: Abstract Background and Purpose: Multiple renal volumetric assessment studies have correlated parenchymal volume with the glomerular filtration rate. The objective of this study was to compare renal volumes before and after treatment of renal masses with either partial nephrectomy or radiofrequency ablation (RFA). PATIENTS AND METHODS: We reviewed our prospectively collected database of patients with renal masses who were treated between November 2001 and January 2011 with robot-assisted laparoscopic partial nephrectomy (RALPN), laparoscopic RFA (LRFA), or CT-guided percutaneous RFA (CTRFA). Digital Imaging and Communications in Medicine CT imaging data were analyzed in an open-source viewer. Volumetric calculations were used to measure the normal, enhancing bilateral renal parenchyma and tumor volumes. Normal parenchymal volume loss was compared among treatments. RESULTS: There were 96 patients (68 men) with an average age of 68.0 (36-84) years who met our inclusion criteria. The average tumor diameter, tumor volume, and nephrometry score (NS) was 3.5 cm, 32.0 cm(3), and 7.1 in RALPN (n=26), 2.6 cm, 9.8 cm(3), and 7.1 in CTRFA (n=47), and 2.9 cm, 14.3 cm(3), and 7.2 in LRFA (n=23) groups. The percent change in the operated kidney volume was similar in RALPN (-12%±15), CTRFA (-13%±16), and LRFA (-17%±18) groups. NS was the only variable in a multivariate linear regression model that correlated with the amount of volume lost in the ipsilateral kidney. CONCLUSIONS: Our retrospective volumetric analysis of renal parenchyma before and after partial nephrectomy or RFA of renal masses revealed that all treatments produce similar volume of collateral damage.

Biopsy features associated with prostate cancer progression in active surveillance patients: comparison of three statistical models.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Active surveillance is an established management option for patients with favourable-risk prostate cancer. However, about 25-30% of active surveillance patients demonstrate biopsy progression within the first 3-5 years of follow-up. Although several factors, such as the results of the diagnostic and surveillance biopsies, are known to be associated with the risk of progression, our ability to accurately predict this risk remains limited. Our analysis demonstrated that the overall number of positive cores in the diagnostic and first surveillance biopsies is strongly associated with the risk of progression in active surveillance patients. Furthermore, combined results of diagnostic and first surveillance biopsies provide more information about the probability of progression than they do separately. The most important variable affecting the progression-free survival was the overall number of cores positive for cancer. By 3 years of active surveillance, most of the patients who had four positive cores in the diagnostic and surveillance biopsies progressed, while those who had only one positive core had an excellent prognosis. These findings could be used to improve the accuracy of assessments of the prognosis of patients with low-risk prostate cancer and to help them make informed decisions about their treatment. OBJECTIVE: To analyse the prognostic importance of information provided by the diagnostic biopsy, the first surveillance biopsy and a combination thereof to identify active surveillance patients with a particularly high risk of progression. MATERIALS AND METHODS: The present study included 161 active surveillance patients who had at least two surveillance biopsies. The first surveillance biopsy was performed within 1 year of the diagnosis. Further surveillance biopsies usually took place every 1-2 years. Progression on the surveillance biopsy was defined as the presence of Gleason 4/5 cancer, > two positive cores or >20% involvement of any core. Cox proportional hazards regression analysis was used to examine the relationship between biopsy characteristics and progression. Three distinct statistical models were built using characteristics of diagnostic biopsies, surveillance biopsies, and a combination thereof. Harrell's c-index was used to quantify the predictive accuracy of each multivariate Cox model. RESULTS: The median follow-up was 3.6 years; 46 (28.6%) patients progressed. In multivariate analysis the major factor associated with progression was the number of positive cores. The model based on the combined results of diagnostic and first surveillance biopsies was significantly more predictive than the models based on the individual results of each biopsy. Patients with four positive cores in the diagnostic and first surveillance biopsies had estimated 5-year progression rate of 100%. CONCLUSION: The total number of positive cores in the diagnostic and first surveillance biopsies provides important information about the risk of prostate cancer progression in active surveillance patients.

Comprehensive analysis of post-diagnostic prostate-specific antigen kinetics as predictor of a prostate cancer progression in active surveillance patients.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: A significant proportion of patients diagnosed with prostate cancer do not require immediate treatment and could be managed by active surveillance, which usually includes serial measurements of prostate-specific antigen (PSA) levels and regular biopsies. The rate of rise in PSA levels, which could be calculated as PSA velocity or PSA doubling time, was previously suggested to be associated with the biological aggressiveness of prostate cancer. Although these parameters are obvious candidates for predicting tumour progression in active surveillance patients, earlier studies that examined this topic provided conflicting results. Our analysis showed that PSA velocity and PSA doubling time calculated at different time-points, by different methods, over different intervals, and in different sub-groups of active surveillance patients provide little if any prognostic information. Although we found some significant associations between PSA velocity and the risk of progression as determined by biopsy, the actual clinical significance of this association was small. Furthermore, PSA velocity did not add to the predictive accuracy of total PSA. OBJECTIVE: To study whether prostate-specific antigen (PSA) velocity (PSAV) and PSA doubling time (PSADT) are associated with biopsy progression in patients managed by active surveillance. PATIENTS AND METHODS: Our inclusion criteria for active surveillance are biopsy Gleason sum <7, two or fewer positive biopsy cores, ≤20% tumour present in any core, and clinical stage T1-T2a. Changes in any of these parameters during the follow-up that went beyond these limits are considered to be progression. This study included 250 patients who had at least one surveillance biopsy, an available PSA measured no earlier than 3 months before diagnosis, and at least one PSA measurement before each surveillance biopsy. We evaluated the association between PSA kinetics and progression at successive surveillance biopsies in different sub-groups of patients by calculating the area under the curve (AUC) as well as sensitivity and specificity of different thresholds. RESULTS: Over a median follow-up of 3.0 years, the disease of 64 (26%) patients progressed. PSADT was not associated with biopsy progression, whereas PSAV was only weakly associated with progression in certain sub-groups. However, incorporation of PSAV in models including total PSA resulted in a moderate increase in AUC only when the entire cohort was analysed. In other sub-groups the predictive accuracy of total PSA was not significantly improved by adding PSAV. CONCLUSIONS: Our findings confirm that PSA kinetics should not be used in decision-making in patients with low-risk prostate cancer managed by active surveillance. Regular surveillance biopsies should remain as the principal method of monitoring cancer progression in these men.

Partial sampling of radical prostatectomy specimens: detection of positive margins and extraprostatic extension.

Currently there is no global agreement as to how extensively a radical prostatectomy specimen should be sectioned and histologically examined. We analyzed the ability of different methods of partial sampling in detecting positive margin (PM) and extraprostatic extension (EPE)-2 pathologic features of prostate cancer that are most easily missed by partial sampling of the prostate. Radical prostatectomy specimens from 617 patients treated with open radical prostatectomy between 1992 and 2011 were analyzed. Examination of the entirely submitted prostate detected only PM in 370 (60%), only EPE in 100 (16%), and both in 147 (24%) specimens. We determined whether these pathologic features would have been diagnosed had the examination of the specimen been limited only to alternate sections (method 1), alternate sections representing the posterior aspect of the gland in addition to one of the mid-anterior aspects (method 2), and every section representing the posterior aspect of the gland in addition to one of the mid-anterior aspects, supplemented by the remaining ipsilateral anterior sections if a sizeable tumor is seen (method 3). Methods 1 and 2 missed 13% and 21% of PMs and 28% and 47% of EPEs, respectively. Method 3 demonstrated better results missing only 5% of PMs and 7% of EPEs. Partial sampling techniques missed slightly more PMs and EPEs in patients with low-risk to intermediate-risk prostate cancer, although even in high-risk cases none of the methods detected all of the studied aggressive pathologic features.

Prognostic implications of partial sampling of radical prostatectomy specimens: comparison of 3 methods.

PURPOSE: We analyzed the prognostic implications of positive margins and extraprostatic extension missed by different methods of partially sampling prostatectomy specimens. MATERIALS AND METHODS: The study group consisted of 1,499 patients treated with radical prostatectomy. All specimens were processed uniformly and submitted entirely. For each patient with a positive margin or extraprostatic extension we determined whether these pathological characteristics would have been diagnosed had the specimen been examined by 3 partial sampling techniques. The Harrell concordance index was used to quantify the predictive performance of the Cox models based on the potential findings of the different sampling methods. RESULTS: Partial sampling methods 1 and 2, which included the examination of alternate slides, missed 13% to 21% of positive margins and 27% to 46% of extraprostatic extensions. The effect on biochemical recurrence-free survival of these undetected pathological features was similar to that of positive margins and extraprostatic extension that would have been diagnosed by corresponding techniques. Method 3, which sampled the entire posterior region, the mid anterior prostate and the rest of the ipsilateral anterior gland (if sizeable tumor was seen), detected 95% of positive margins and 94% of extraprostatic extensions. The extraprostatic extension missed by this method was not associated with a significant increase in the risk of biochemical recurrence. The Harrell concordance index of the multivariate models was 0.806, 0.797, 0.795 and 0.804 based on the results of complete sampling, and methods 1, 2 and 3, respectively. CONCLUSIONS: Examining alternate sections of prostatectomy specimen results in missing clinically important positive margins and extraprostatic extension. It decreases our ability to predict biochemical recurrence-free survival.