Jeffrey S. Montgomery

Accuracy of Determining Small Renal Mass Management with Risk Stratified Biopsies: Confirmation by Final Pathology

PURPOSE We assess the accuracy of a biopsy directed treatment algorithm in correctly assigning active surveillance vs treatment in patients with small renal masses by comparing biopsy results with final surgical pathology. MATERIALS AND METHODS From 1999 to 2011, 151 patients with small renal masses 4 cm or smaller underwent biopsy and subsequent surgical excision. Biopsy revealed cell type and grade in 133 patients, allowing the hypothetical assignment of surveillance vs treatment using an algorithm incorporating small renal mass size and histological risk group. We compared the biopsy directed management recommendation with the ideal management as defined by final surgical pathology. RESULTS Biopsy called for surveillance of 36 small renal masses and treatment of 97 small renal masses. Final pathology showed 11 patients initially assigned to surveillance should have been assigned to treatment (8.3% of all patients, 31% of those recommended for surveillance), whereas no patients moved from treatment to surveillance. Agreement between biopsy and final pathology was 92%. Using management based on final pathology as the reference standard, biopsy had a negative predictive value of 0.69 and positive predictive value 1.0 for determining management. Of the 11 misclassified cases, 7 had a biopsy indicating grade 1 clear cell renal cancer which was upgraded to grade 2 (5) or grade 3 (2). After modifying the histological risk group assignment to account for undergrading of clear cell renal cancer, agreement improved to 97%, with a negative predictive value of 0.86 and a positive predictive value of 1.0. CONCLUSIONS Our results suggest that compared to final pathology, biopsy of small renal masses accurately informs an algorithm incorporating size and histological risk group that directs the management of small renal masses.

Racial Variation in CAG Repeat Lengths Within the Androgen Receptor Gene Among Prostate Cancer Patients of Lower Socioeconomic Status

PURPOSE To evaluate (1) whether there were racial differences in the androgen receptor gene CAG repeat length and in clinical or laboratory attributes of prostate cancer at the time of diagnosis; (2) whether there were differences in race, Gleason score, prostate-specific antigen (PSA) level, and stage at diagnosis by androgen receptor gene CAG repeat length; and (3) whether sociodemographic, clinical, and laboratory based factors might be associated with advanced-stage prostate cancer. To our knowledge, our study is the first to report on CAG repeat lengths in a cohort of prostate cancer patients, which includes large numbers of African-American men. METHODS CAG repeat lengths on the androgen receptor gene were evaluated for 151 African-American and 168 white veterans with prostate cancer. The chi(2) test, t test, and logistic regression analyses were used to evaluate the associations between CAG repeat lengths and race, stage, histologic grade, and PSA levels at diagnosis. RESULTS The mean age of the cohort at the time of diagnosis was 68.7 years. At presentation, 42.0% had stage D prostate cancer, 26.5% had Gleason scores of 8 to 10, and 53.0% had PSA levels >/= 10 ng/dL. Mean androgen receptor gene CAG repeat length for white veterans was 21.9 (SD, 3.5) versus 19.8 (SD, 3.2) for African-American veterans (P =.001). Men with shorter CAG repeats were more likely to have stage D prostate cancer (P =.09) but were not more likely to have a higher PSA concentration or Gleason score. CONCLUSION In this cohort of men with prostate cancer, short CAG repeat length on the androgen receptor gene was associated with African-American race and possibly with higher stage but not with other clinical or pathologic findings.

Multicenter Assessment of Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer

BACKGROUND The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. OBJECTIVE We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. INTERVENTION NAC and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. RESULTS AND LIMITATIONS Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6). CONCLUSIONS Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. PATIENT SUMMARY There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.

Variant (divergent) histologic differentiation in urothelial carcinoma is under-recognized in community practice: Impact of mandatory central pathology review at a large referral hospital

BACKGROUND AND OBJECTIVE Urothelial carcinoma (UC) demonstrating variant histologic differentiation is associated with poor outcomes, and certain variants exhibit differing therapeutic responses compared with pure conventional UC. Little is known about the awareness and reporting practices of UC with variant histology in community practice. MATERIALS AND METHODS Patients diagnosed with UC based on an outside pathologic review had their pathology centrally reviewed before instituting therapy. A discordant diagnosis was defined as the presence of variant histologic differentiation not reported by the referring institution. Variant histologic differentiation was quantitated as focal (10%-50%) or extensive (>50%). RESULTS Of 589 transurethral biopsies (TURBTs), 115 (19.5%) UCs demonstrated variant histologic differentiation. Muscle invasion at TURBT and extravesical disease at cystectomy was present in 69% and 52%, respectively. Of 56 patients with at least 1 year follow-up, recurrence-free survival was 56%. The majority (90%) showed a single variant histology, which was extensive in 58% of cases. Squamous differentiation (32%) was the most common variant histology identified, followed by small cell (16%), glandular (13%), micropapillary (12%), nested (8%), sarcomatoid (6%), lymphoepithelial (3%), and plasmacytoid (1%) type. Variant histologic differentiation was not documented by the referring institution in 44% of cases, of which 47% were extensive. Commonly under-recognized patterns included lymphoepithelial (2) and plasmacytoid (1) types (100%), nested (7, 87%), micropapillary (10, 83%), and small cell (7, 44%). CONCLUSIONS This study emphasizes the importance of central pathology review in the management of bladder cancer patients and the need for increased awareness of this relatively common phenomenon in UC.

A Matched Comparison of Perioperative Outcomes of a Single Laparoscopic Surgeon Versus a Multisurgeon Robot-Assisted Cohort for Partial Nephrectomy

PURPOSE Minimally invasive nephron sparing surgery is gaining popularity for small renal masses. Few groups have evaluated robot-assisted partial nephrectomy compared to other approaches using comparable patient populations. We present a matched pair analysis of a heterogeneous group of surgeons who performed robot-assisted partial nephrectomy and a single experienced laparoscopic surgeon who performed conventional laparoscopic partial nephrectomy. Perioperative outcomes and complications were compared. MATERIALS AND METHODS All 249 conventional laparoscopic and robot-assisted partial nephrectomy cases from January 2007 to June 2010 were reviewed from our prospectively maintained institutional database. Groups were matched 1:1 (108 matched pairs) by R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines) nephrometry score, transperitoneal vs retroperitoneal approach, patient age and hilar nature of the tumor. Statistical analysis was done to compare operative outcomes and complications. RESULTS Matched analysis revealed that nephrometry score, age, gender, tumor side and American Society of Anesthesia physical status classification were similar. Operative time favored conventional laparoscopic partial nephrectomy. During the study period robot-assisted partial nephrectomy showed significant improvements in estimated blood loss and warm ischemia time compared to those of the experienced conventional laparoscopic group. Postoperative complication rates, and complication distributions by Clavien classification and type were similar for conventional laparoscopic and robot-assisted partial nephrectomy (41.7% and 35.0%, respectively). CONCLUSIONS Robot-assisted partial nephrectomy has a noticeable but rapid learning curve. After it is overcome the robotic procedure results in perioperative outcomes similar to those achieved with conventional laparoscopic partial nephrectomy done by an experienced surgeon. Robot-assisted partial nephrectomy likely improves surgeon and patient accessibility to minimally invasive nephron sparing surgery.

The RAZOR (randomized open vs robotic cystectomy) trial: Study design and trial update

The purpose of the RAZOR (randomized open vs robotic cystectomy) study is to compare open radical cystectomy (ORC) vs robot‐assisted RC (RARC), pelvic lymph node dissection (PLND) and urinary diversion for oncological outcomes, complications and health‐related quality of life (HRQL) measures with a primary endpoint of 2‐year progression‐free survival (PFS). RAZOR is a multi‐institutional, randomized, non‐inferior, phase III trial that will enrol at least 320 patients with T1–T4, N0–N1, M0 bladder cancer with ≈160 patients in both the RARC and ORC arms at 15 participating institutions. Data will be collected prospectively at each institution for cancer outcomes, complications of surgery and HRQL measures, and then submitted to trial data management services Cancer Research and Biostatistics (CRAB) for final analyses. To date, 306 patients have been randomized and accrual to the RAZOR trial is expected to conclude in 2014. In this study, we report the RAZOR trial experimental design, objectives, data safety, and monitoring, and accrual update. The RAZOR trial is a landmark study in urological oncology, randomizing T1–T4, N0–N1, M0 patients with bladder cancer to ORC vs RARC, PLND and urinary diversion. RAZOR is a multi‐institutional, non‐inferiority trial evaluating cancer outcomes, surgical complications and HRQL measures of ORC vs RARC with a primary endpoint of 2‐year PFS. Full data from the RAZOR trial are not expected until 2016–2017.

Sharpening the focus on causes and timing of readmission after radical cystectomy for bladder cancer

Readmissions after radical cystectomy are common, burdensome, and poorly understood. For these reasons, the authors conducted a population‐based study that focused on the causes of and time to readmission after radical cystectomy.

Disparities in bladder cancer

Among men, bladder cancer is the fourth most common malignancy and ninth leading cause of death from cancer in the United States. In contrast, it is the 11th most common malignancy and 12th leading cause of death from cancer among women. The successful management of bladder cancer largely depends on its timely diagnosis and treatment. Unfortunately, barriers disproportionately delay detection and treatment for individuals with social, economic, and community disadvantages. This imbalance creates health disparities (i.e., differences in health outcomes that are closely linked to these disadvantages), which negatively affect vulnerable populations, such as racial and ethnic minority groups, those from lower socioeconomic classes, and the uninsured. To obtain a better understanding of this issue, we review the current state of bladder cancer disparities research.

Evidence of Perineural Invasion on Prostate Biopsy Specimen and Survival After Radical Prostatectomy

OBJECTIVE To better understand relationships between perineural invasion (PNI) and radical prostatectomy outcomes, we examined whether PNI was independently associated with adverse pathologic features and worse survival outcomes after radical prostatectomy. METHODS PNI is a routinely reported pathologic parameter for prostate biopsy specimens. We identified 3226 patients undergoing radical prostatectomy for clinically localized prostate cancer at our institution between 1994 and 2010. We used multivariable logistic regression models to examine whether PNI was independently associated with extraprostatic extension, seminal vesicle invasion, and surgical margin status. We used Kaplan-Meier methods and the log-rank test to assess disease-free, prostate cancer-specific, and overall survival according to PNI status. Cox proportional hazards modeling was used to evaluate relationships between PNI and survival outcomes. RESULTS PNI was identified in the prostate biopsy specimen in 20% of patients who underwent radical prostatectomy. Patients with PNI were more likely to have adverse pathologic features, including extraprostatic extension, seminal vesicle invasion, and positive surgical margins. Patients with PNI had shorter disease-free, cancer-specific, and overall survival (all log-rank P <.001). After adjustment for adverse pathologic features at radical prostatectomy, PNI was independently associated with disease-free survival (adjusted hazard ratio, 1.45; 95% confidence interval, 1.09-1.92) and overall survival (hazard ratio, 1.57; 95% confidence interval, 1.13-2.18). CONCLUSION PNI was independently associated with adverse pathologic features and worse survival outcomes after radical prostatectomy. For these reasons, PNI on prostate biopsy specimens should be considered in prostate cancer treatment decision making and clinical care.

Association of RENAL nephrometry score with outcomes of minimally invasive partial nephrectomy

To evaluate the predictive value of the Radius, Exophytic, Nearness, Anterior, Location nephrometry scoring system and to investigate the influence of its individual components on perioperative outcomes of minimally invasive partial nephrectomy.