Phillip M. Pierorazio

Upgrading and Downgrading of Prostate Cancer from Biopsy to Radical Prostatectomy: Incidence and Predictive Factors Using the Modified Gleason Grading System and Factoring in Tertiary Grades

BACKGROUND Prior studies assessing the correlation of Gleason score (GS) at needle biopsy and corresponding radical prostatectomy (RP) predated the use of the modified Gleason scoring system and did not factor in tertiary grade patterns. OBJECTIVE To assess the relation of biopsy and RP grade in the largest study to date. DESIGN, SETTING, AND PARTICIPANTS A total of 7643 totally embedded RP and corresponding needle biopsies (2004-2010) were analyzed according to the updated Gleason system. INTERVENTIONS All patients underwent prostate biopsy prior to RP. MEASUREMENTS The relation of upgrading or downgrading to patient and cancer characteristics was compared using the chi-square test, Student t test, and multivariable logistic regression. RESULTS AND LIMITATIONS A total of 36.3% of cases were upgraded from a needle biopsy GS 5-6 to a higher grade at RP (11.2% with GS 6 plus tertiary). Half of the cases had matching GS 3+4=7 at biopsy and RP with an approximately equal number of cases downgraded and upgraded at RP. With biopsy GS 4+3=7, RP GS was almost equally 3+4=7 and 4+3=7. Biopsy GS 8 led to an almost equal distribution between RP GS 4+3=7, 8, and 9-10. A total of 58% of the cases had matching GS 9-10 at biopsy and RP. In multivariable analysis, increasing age (p<0.0001), increasing serum prostate-specific antigen level (p<0.0001), decreasing RP weight (p<0.0001), and increasing maximum percentage cancer/core (p<0.0001) predicted the upgrade from biopsy GS 5-6 to higher at RP. Despite factoring in multiple variables including the number of positive cores and the maximum percentage of cancer per core, the concordance indexes were not sufficiently high to justify the use of nomograms for predicting upgrading and downgrading for the individual patient. CONCLUSIONS Almost 20% of RP cases have tertiary patterns. A needle biopsy can sample a tertiary higher Gleason pattern in the RP, which is then not recorded in the standard GS reporting, resulting in an apparent overgrading on the needle biopsy.

Prognostic Gleason grade grouping: data based on the modified Gleason scoring system

The Gleason scoring system is a well‐established predictor of pathological stage and oncological outcomes for men with prostate cancer. Modifications throughout the last few decades – most recently by the International Society of Urological Pathology (ISUP) in 2005 – have attempted to improve the correlation between biopsy and radical prostatectomy Gleason sum and better stratify patients to predict clinical outcomes. Based on these clinical outcomes and the excellent prognosis for patients with low Gleason scores, we recommend Gleason grades incorporating a prognostic grade grouping which accurately reflect prognosis and are clearly understood by physicians and patients alike.

Laparoendoscopic Single-site Surgery in Urology: Worldwide Multi-institutional Analysis of 1076 Cases

BACKGROUND Laparoendoscopic single-site surgery (LESS) has gained popularity in urology over the last few years. OBJECTIVE To report a large multi-institutional worldwide series of LESS in urology. DESIGN, SETTING, AND PARTICIPANTS Consecutive cases of LESS done between August 2007 and November 2010 at 18 participating institutions were included in this retrospective analysis. INTERVENTION Each group performed a variety of LESS procedures according to its own protocols, entry criteria, and techniques. MEASUREMENTS Demographic data, main perioperative outcome parameters, and information related to the surgical technique were gathered and analyzed. Conversions to reduced-port laparoscopy, conventional laparoscopy, or open surgery were evaluated, as were intraoperative and postoperative complications. RESULTS AND LIMITATIONS Overall, 1076 patients were included in the analysis. The most common procedures were extirpative or ablative operations in the upper urinary tract. The da Vinci robot was used to operate on 143 patients (13%). A single-port technique was most commonly used and the umbilicus represented the most common access site. Overall, operative time was 160±93 min and estimated blood loss was 148±234 ml. Skin incision length at closure was 3.5±1.5 cm. Mean hospital stay was 3.6±2.7 d with a visual analog pain score at discharge of 1.5±1.4. An additional port was used in 23% of cases. The overall conversion rate was 20.8%; 15.8% of patients were converted to reduced-port laparoscopy, 4% to conventional laparoscopy/robotic surgery, and 1% to open surgery. The intraoperative complication rate was 3.3%. Postoperative complications, mostly low grade, were encountered in 9.5% of cases. CONCLUSIONS This study provides a global view of the evolution of LESS in the field of minimally invasive urologic surgery. A broad range of procedures have been effectively performed, primarily in the academic setting, within diverse health care systems around the world. Since LESS is performed by experienced laparoscopic surgeons, the risk of complications remains low when stringent patient-selection criteria are applied.

Trends in Renal Surgery: Robotic Technology is Associated with Increased Use of Partial Nephrectomy

PURPOSE Underuse of partial vs radical nephrectomy for renal tumors was noted in recent population based analyses. An explanation is the learning curve associated with laparoscopic partial nephrectomy. We analyzed state trends in renal surgery and their relationship to the introduction of robotic technology. MATERIALS AND METHODS We used the Maryland HSCRC (Health Services Cost Review Commission) database to identify patients who underwent radical or partial nephrectomy, or renal ablation from 2000 to 2011. Utilization trends, and associated patient and hospital factors were analyzed using multivariate logistic regression. ICD-9 robotic modifier codes were established in October 2008. RESULTS Of the 14,260 patients included in analysis 11,271 (79.0%), 2,622 (18.4%) and 367 (2.6%) underwent radical and partial nephrectomy, and renal ablation, respectively. Partial nephrectomy increased from 8.6% in 2000 to 27% in 2011. Open radical nephrectomy decreased by 33%, while minimally invasive radical nephrectomy increased by 15%. Robot-assisted laparoscopic partial nephrectomy increased from 2008 to 2011, attaining a 14% rate at university and 10% at nonuniversity hospitals (p = 0.03). It was associated with increased partial nephrectomy (OR 9.67, p <0.001). Younger age, male gender and low patient complexity predicted partial nephrectomy on overall analysis, while higher hospital volume and university status were predictors only in earlier years. CONCLUSIONS Partial nephrectomy use increased in Maryland from 2001 to 2011, which was facilitated by robotic technology. Associations with hospital factors decreased with time. These data suggest that robotic technology may enable surgeons across practice settings to more frequently perform nephron sparing surgery.

Robotic-assisted Versus Traditional Laparoscopic Partial Nephrectomy: Comparison of Outcomes and Evaluation of Learning Curve

OBJECTIVES To examine the transition to robot-assisted laparoscopic partial nephrectomy (RALPN) from pure laparoscopic partial nephrectomy (LPN) and investigate the learning curve (LC). RALPN has emerged as a minimally invasive alternative to nephron-sparing surgery. METHODS A total of 150 consecutive patients were identified who underwent LPN or RALPN in the initial experience of a single surgeon since 2006. The perioperative data were evaluated using appropriate comparative tests. The LC was investigated by examining the operative times, warm ischemia times (WITs), and estimated blood loss (EBL) in groups of 25 consecutive patients. To account for laparoscopic LC, the outcomes of patients who underwent surgery in 2009 or later were also compared. RESULTS Of the 150 patients, 102 and 48 underwent LPN and RALPN, respectively. The patient and tumor characteristics were similar. The mean operative time (193 vs 152 minutes, P < .001), WIT (18.0 vs 14.0, P < .001), and EBL (245 vs 122 mL, P = .001) favored RALPN. Improvements in the operative time (P = .01), WIT (P = .006), and EBL (P = .01) were noted as experience increased in the LPN cohort and was most pronounced after the first 25 LPN patients. Since 2009, 55 and 44 patients underwent LPN and RALPN, respectively. Although the absolute differences were less, the operative time (182 vs 150, P < .001), WIT (15.3 vs 13.3, P < .001), and EBL (206 vs 118, P = .005) favored RALPN. CONCLUSIONS RALPN appears to have shorter operative and ischemia times and less blood loss compared with LPN. After a LC of approximately 25 cases, the transition from LPN to RALPN can be undertaken without an additional LC and can be associated with immediate benefits.

THE INCREASING USE OF INTRAVESICAL THERAPIES FOR STAGE T1 BLADDER CANCER COINCIDES WITH DECREASING SURVIVAL AFTER CYSTECTOMY

Intravesical therapy (IVT), chemo and immunotherapy, has made conservative, bladder‐sparing strategies a viable option for managing patients with high grade T1 bladder cancer. However, many of these patients will have recurrence and occasionally progression, questioning delayed intervention. This study examines the patterns of use of IVT in high‐grade T1 bladder cancer and the subsequent impact on survival for patients ultimately proceeding to radical cystectomy (RC).

Five-year Analysis of a Multi-institutional Prospective Clinical Trial of Delayed Intervention and Surveillance for Small Renal Masses: The DISSRM Registry ☆

BACKGROUND A growing body of retrospective literature is emerging regarding active surveillance (AS) for patients with small renal masses (SRMs). There are limited prospective data evaluating the effectiveness of AS compared to primary intervention (PI). OBJECTIVE To determine the characteristics and clinical outcomes of patients who chose AS for management of their SRM. DESIGN, SETTING, AND PARTICIPANTS From 2009 to 2014, the multi-institutional Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry prospectively enrolled 497 patients with solid renal masses ≤4.0cm who chose PI or AS. INTERVENTION AS versus PI. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The registry was designed and powered as a noninferiority study based on historic recurrence rates for PI. Analyses were performed in an intention-to-treat manner. Primary outcomes were overall survival (OS) and cancer-specific survival (CSS). RESULTS AND LIMITATIONS Of the 497 patients enrolled, 274 (55%) chose PI and 223 (45%) chose AS, of whom 21 (9%) crossed over to delayed intervention. AS patients were older, had worse Eastern Cooperative Oncology Group scores, total comorbidities, and cardiovascular comorbidities, had smaller tumors, and more often had multiple and bilateral lesions. OS for PI and AS was 98% and 96% at 2 yr, and 92% and 75% at 5 yr, respectively (log rank, p=0.06). At 5 yr, CSS was 99% and 100% for PI and AS, respectively (p=0.3). AS was not predictive of OS or CSS in regression modeling with relatively short follow-up. CONCLUSIONS In a well-selected cohort with up to 5 yr of prospective follow-up, AS was not inferior to PI. PATIENT SUMMARY The current report is among the first prospective analyses of patients electing for active surveillance of a small renal mass. Discussion of active surveillance should become part of the standard discussion for management of small renal masses.

Serum testosterone is associated with aggressive prostate cancer in older men: results from the Baltimore Longitudinal Study of Aging

Study Type – Prognosis (inception cohort)
Level of Evidence 1b

Management of Renal Masses and Localized Renal Cancer: Systematic Review and Meta-Analysis

PURPOSE Several options exist for management of clinically localized renal masses suspicious for cancer, including active surveillance, thermal ablation and radical or partial nephrectomy. We summarize evidence on effectiveness and comparative effectiveness of these treatment approaches for patients with a renal mass suspicious for localized renal cell carcinoma. MATERIALS AND METHODS We searched MEDLINE®, Embase® and the Cochrane Central Register of Controlled Trials from January 1, 1997 through May 1, 2015. Paired investigators independently screened articles to identify controlled studies of management options or cohort studies of active surveillance, abstracted data sequentially and assessed risk of bias independently. Strength of evidence was graded by comparisons. RESULTS The search identified 107 studies (majority T1, no active surveillance or thermal ablation stratified outcomes of T2 tumors). Cancer specific survival was excellent among all management strategies (median 5-year survival 95%). Local recurrence-free survival was inferior for thermal ablation with 1 treatment but reached equivalence to other modalities after multiple treatments. Overall survival rates were similar among management strategies and varied with age and comorbidity. End-stage renal disease rates were low for all strategies (0.4% to 2.8%). Radical nephrectomy was associated with the largest decrease in estimated glomerular filtration rate and highest incidence of chronic kidney disease. Thermal ablation offered the most favorable perioperative outcomes. Partial nephrectomy showed the highest rates of urological complications but overall rates of minor/major complications were similar among interventions. Strength of evidence was moderate, low and insufficient for 11, 22 and 30 domains, respectively. CONCLUSIONS Comparative studies demonstrated similar cancer specific survival across management strategies, with some differences in renal functional outcomes, perioperative outcomes and postoperative harms that should be considered when choosing a management strategy.

Grade Heterogeneity in Small Renal Masses: Potential Implications for Renal Mass Biopsy

PURPOSE Understanding the degree of phenotypic heterogeneity in a small renal mass may have implications for interpreting renal mass biopsy data. In this study we quantify nuclear grade heterogeneity in small renal masses. MATERIALS AND METHODS Our institutional renal mass database was queried for patients with T1a (less than 4 cm) renal masses stratified by the criteria of imaging diameter less than 2 cm or 2 cm or greater, clear cell or papillary histology, low grade (Fuhrman 1-2) or high grade (Fuhrman 3-4) with tissue available for review. Four consecutive specimens were chosen from each of the 8 strata for a total of 32. All specimens were reanalyzed and the highest Fuhrman grade present in each 10× powered field was recorded. A case was classified as heterogeneous if multiple grades were present and as discordant if the highest Fuhrman grade was present in less than 50% of the specimen. RESULTS A median of 5 slides (IQR 3.5-7.5) and 59, 10× powered fields (IQR 34-109) were examined per patient. Overall 26 samples (81.3%) were heterogeneous, including 15 of 16 (93.8%) high grade specimens. Among all cases 10 (31.3%) were discordant and of high grade specimens 4 (25%) were discordant. Median fraction of low grade tissue in high grade specimens was 38.9% (IQR 12.2-57.2). CONCLUSIONS The majority of small renal masses demonstrated considerable nuclear grade heterogeneity. The greatest degree of heterogeneity and discordance was observed in high grade tumors. One should consider these findings when interpreting renal mass biopsy data as the risk of under sampling high grade tumors may not be insignificant.