Jasmir G. Nayak

Pathological Upstaging of Clinical T1 to Pathological T3a Renal Cell Carcinoma: A Multi-institutional Analysis of Short-term Outcomes

OBJECTIVE To determine the oncological impact of pathological upstaging among patients with clinical T1 (cT1) disease treated by partial nephrectomy or radical nephrectomy. METHODS The Canadian Kidney Cancer Information System comprises a prospectively maintained multi-institutional database for patients with renal cell carcinoma. Nonmetastatic, cT1 renal cell carcinoma cases were evaluated. Upstaging was defined as pathological T3a disease. Multivariate Cox regression analysis identified predictors for recurrence (local recurrence and/or metastatic disease) whereas logistic regression identified predictors of pathological upstaging. Kaplan-Meier methods estimated survival. RESULTS Of 1448 eligible cT1 patients, upstaging was observed in 134 (9%). One thousand fifty-eight (73%) were treated by partial nephrectomy. After a median follow-up of 23 months, the 3-year recurrence-free survival was 76% in upstaged patients compared with 93% in those not upstaged (P < .001). Controlling for age, gender, year of surgery, histology, tumor size, surgical approach, and margin status, pathological upstaging was independently associated with disease recurrence (hazard ratio 2.03, 95% confidence interval [CI] 1.12-3.68). Increasing age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), Fuhrman grade (OR 2.47, 95% CI 1.47-4.14), and tumor size (OR 1.16, 95% CI 1.00-1.36) were independently associated with a risk of pathological upstaging. CONCLUSION Pathological upstaging confers a negative prognosis and highlights the importance of accurate clinical staging. A number of factors have been identified, including some attainable by renal biopsy, which may predict upstaging and provide valuable adjunct information to inform risk stratification and management decisions among patients with cT1 renal masses.

Relevance of graph literacy in the development of patient-centered communication tools

OBJECTIVE To determine the literacy skill sets of patients in the context of graphical interpretation of interactive dashboards. METHODS We assessed literacy characteristics of prostate cancer patients and assessed comprehension of quality of life dashboards. Health literacy, numeracy and graph literacy were assessed with validated tools. We divided patients into low vs. high numeracy and graph literacy. We report descriptive statistics on literacy, dashboard comprehension, and relationships between groups. We used correlation and multiple linear regressions to examine factors associated with dashboard comprehension. RESULTS Despite high health literacy in educated patients (78% college educated), there was variation in numeracy and graph literacy. Numeracy and graph literacy scores were correlated (r=0.37). In those with low literacy, graph literacy scores most strongly correlated with dashboard comprehension (r=0.59-0.90). On multivariate analysis, graph literacy was independently associated with dashboard comprehension, adjusting for age, education, and numeracy level. CONCLUSIONS Even among higher educated patients; variation in the ability to comprehend graphs exists. PRACTICE IMPLICATIONS Clinicians must be aware of these differential proficiencies when counseling patients. Tools for patient-centered communication that employ visual displays need to account for literacy capabilities to ensure that patients can effectively engage these resources.

Patient-centered risk stratification of disposition outcomes following radical cystectomy.

PURPOSE Patient-centered care involves providing understandable information to facilitate individualized health decisions among patients. We sought to determine the effect of age and comorbidity status on clinically meaningful outcomes following radical cystectomy (RC), in an effort the help optimize patient selection and enhance discussions among those considering surgery. MATERIALS AND METHODS In a retrospective review, 6,460 patients were treated with RC for bladder cancer from the U.S. Premier Perspectives Database between 2007 and 2013. The influence of age and comorbidity count on the rates of inpatient mortality, prolonged length of stay (LOS), disposition to other than home and hospital readmission within the month of surgery or month after, were assessed. Comorbidity was calculated using the Elixhauser method. Prolonged LOS was defined as >10 days. Multivariable logistic regression models were used. RESULTS Following RC, 16% of patients were discharged to somewhere other than home, 37% had a prolonged LOS and 2% died during the index admission. Among those discharged home after surgery, 27% of patients were readmitted. Prolonged LOS was associated with increasing comorbidities and age >70 years (P < 0.001). The adjusted likelihood of readmission increased with increasing burden of comorbid conditions (P < 0.001), however, not with age. The likelihood of being discharged to other than home increased with age and comorbidity count (P < 0.001). Mortality was associated with ≥3 comorbidities and age >70 years. CONCLUSIONS Increasing age and comorbidity are associated with poorer outcomes following RC, with comorbidity being the predominant factor. Our findings may improve surgical selection and better align patient expectations following surgery by providing estimated rates of postoperative events for patients considering RC.

Characterizing the Morbidity of Postchemotherapy Retroperitoneal Lymph Node Dissection for Testis Cancer in a National Cohort of Privately Insured Patients

OBJECTIVE To characterize morbidity of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for testis cancer, we analyze a contemporary national database. PC-RPLND is the standard for residual radiographic masses ≥1 cm (nonseminoma) and positron emission tomography-avid masses ≥3 cm (seminoma). Morbidity for PC-RPLND is greater than primary RPLND, which may be mitigated by performing surgery at a high-volume cancer center. METHODS Current Procedural Terminology and International Classification of Diseases, Ninth Edition codes identified men with testis cancer undergoing PC- or primary RPLND in MarketScan (2007-2012). Multivariable logistic regression assessed factors associated with receiving adjunctive procedures (ie, nephrectomy, vascular reconstruction), prolonged hospitalization, and 90-day readmission. Geographic variables assessed regionalization of PC-RPLND. RESULTS Of 559 men with claims for PC- or primary RPLND (206, 37% PC-RPLND), 19% of PC-RPLND underwent adjunctive procedures (vs 1% among RPLND, P  <  .01). For PC-RPLND, the nephrectomy rate was 10% and the vascular reconstruction rate was 8%. On multivariable analysis, PC-RPLND was associated with undergoing adjunctive procedures (odds ratio 41.9; 95% confidence interval 11.7, 150) and prolonged hospitalization (odds ratio 3.75; 95% confidence interval 1.68, 8.42) compared to primary RPLND. PC-RPLND was not associated with 90-day readmission. Up to 29% of PC-RPLNDs are performed in centers, billing just a single case through MarketScan in the 6 years studied. CONCLUSION PC-RPLND is associated with adjunctive procedures and longer hospitalizations. Given the morbidity of PC-RPLND in this young patient population, efforts are needed to establish quality benchmarks for, reduce the morbidity of, and to accurately discriminate risk during patient discussions prior to this complex, specialized surgery.

A primer on tumour immunology and prostate cancer immunotherapy

Prostate cancer is the most commonly diagnosed non-cutaneous malignancy and the third leading cause of cancer death in Canadian men.1 Despite this incidence and the significant health burden associated with prostate cancer, its management over the last decade has become increasingly complex and controversial for both early and advanced disease. Recent recommendations questioning the benefit of prostate-specific antigen (PSA) screening2 have highlighted the requirement to uncouple the diagnosis from treatment for localized disease in order to reduce over-treatment of biologically indolent disease.3 In the meanwhile, trends to decreased screening in an aging population could result in significant increases in men with more advanced disease requiring salvage or palliative treatment, including androgen-deprivation therapy (ADT) and systemic chemotherapy. Despite recent interest in the earlier delivery of cytotoxic chemotherapeutics for men with advanced disease, prostate cancer remains, for the most part, androgen-dependent. In a non-curative setting, ADT remains a mainstay of treatment. Although most patients are initially responsive, progression to castration-resistant prostate cancer (CRPC) eventually occurs and is associated with a median time until death of less than three years.4 Nevertheless, this past decade has seen substantial improvements in the management of CRPC.5 Docetaxel, approved by Health Canada in 2005, was the first drug to demonstrate survival benefit for men with metastatic CRPC. An increasing understanding of the mechanisms of survival in prostate cancer cells with castrate levels of serum testosterone has led to multiple new therapies, including bone-targeted agents and next-generation androgen receptor inhibitors.5 Overall, these new therapeutic modalities have led to improvements in the quantity and quality of life of men with CRPC. Unfortunately, progression to a chemo-resistant, androgenindependent state is the norm. Exploring other therapeutics, including those processes and pathways involved in resistance to standard therapies, is key to further improving the quality and quantity of life of these patients. Immunotherapy represents one potentially innovative and complementary management strategy for those with advanced prostate cancers. In April 2010, the FDA approved Sipuleucel-T vaccine for the treatment of metastatic CRPC patients, making it the first therapeutic vaccine for any cancer.6 Less than a year later, the immune-stimulating drug ipilimumab was approved for the treatment of metastatic melanoma, ushering in even more focus on the potential of cancer immunotherapy.7 Recent advances in our understanding of immune interactions with cancer cells, leading to these and other successful therapeutic strategies to harness the power of the patient’s own immune system, mark the beginning of an exciting new era in cancer management. For urologists, medical oncologists, and other clinicians that regularly care for men with prostate cancer, remaining up-to-date with these new therapies and their underlying immunological concepts will allow them to offer, and better explain, the most appropriate therapies for their patients. Here we review the basic concepts in tumour immunology that underlie cancer immunotherapy with a primary focus on prostate cancer immunotherapies.

Laparoscopic nephroureterectomy in a patient with a left ventricular assist device

Left ventricular assist device (LVAD) therapy is an established treatment option for select patients with advanced heart failure. Advances in technology and patient management have resulted in improved post-implant outcomes. Consequently, more patients with LVADs are presenting for evaluation and care of non-cardiac surgical disease. However, there is a paucity of literature regarding the optimal perioperative and surgical management of such patients. We present the case of a 71-year-old male with a HeartMate II (Thoratec Corporation, Pleasanton, CA) LVAD, who underwent a laparoscopic left nephroureterectomy for an upper urinary tract transitional cell carcinoma. His perioperative course was uneventful due to the multidisciplinary efforts of cardiac surgery, cardiac anesthesia, nephrology and urology. To our knowledge, this is the first reported case of a laparoscopic nephroureterectomy in a patient with a HeartMate II LVAD.

The impact of fellowship training on pathological outcomes following radical prostatectomy: a population based analysis

BackgroundRadical prostatectomy (RP) is a common treatment for prostate cancer (PCa). Morbidity, mortality and pathological outcomes may be superior in academic institutions. One explanation may be the involvement of oncology fellowship trained urologists within academic institutions. The literature examining pathological outcomes often lacks individual surgeon data. The objective of this study was to compare pathological outcomes following RP between fellowship trained and non-fellowship trained urologists.MethodsPopulation-based, retrospective chart review of men diagnosed with PCa between 2003 and 2008, the majority treated with open approach RP (>99%). Pathological outcomes were compared between oncology fellowship trained academic (FTA), non-fellowship trained academic (NFTA) and non-academic (NA) urologists. Relationships with pathological outcomes were examined utilizing multivariable logistic regression.Results83.1% of eligible patients were included in our analysis resulting in 1075 patients. In multivariable analysis, surgeon group was an independent predictor of positive surgical margin (PSM) (p < 0.0001). NFTA and NA urologists were more likely to have PSM compared to FTA urologists (OR 2.50; 95% CI: 1.44 - 4.35 and OR 2.10; 95% CI: 1.53 - 2.88, respectively). However, the proportion of PSM between NFTA and NA urologists was not significant (p = 0.492). In addition, pathological stage (p = 0.0004), Gleason sum (p < 0.0001), and surgeon volume (p = 0.017) were associated with PSM. Limitations include retrospective design and lack of clinical and functional outcomes.ConclusionsUro-oncology fellowship trained surgeons had significantly lower rates of PSM than non-fellowship trained surgeons in this population based cohort. This study demonstrates the importance of surgeon-related variables on pathological outcomes and highlights the value of additional urologic oncology fellowship training.

Clinical outcomes following laparoscopic management of pT3 renal masses: A large, multi-institutional cohort

INTRODUCTION We described the clinical and oncological outcomes of patients treated by laparoscopic surgery for non-metastatic pT3 renal cell carcinoma (RCC). METHODS We queried a multi-institutional database for patients diagnosed with non-metastatic pathological T3 RCC from 13 Canadian centres treated laparoscopically (radical or partial nephrectomy) between 2008 and 2014. Clinical and pathological outcomes were evaluated. Progression was defined as the development of recurrence or metastatic disease. Log-rank testing and Kaplan-Meier statistical methods assessed for differences and estimated progression-free survival (PFS). RESULTS In total, 176 patients were identified with a median age of 64 years. The median tumour size was 7.0 cm. Pre-clinical stage was cT1 to cT4 in 39%, 28%, 30% and 3%, respectively. The median blood loss was 150 mL (range: 0-6000) and the median operative time was 124 minutes (range: 60-360). Most lesions were clear cell RCC (80%). After a median follow-up of 17.6 months (range: 0.2-75.0), disease progression occurred in 26% (46/176) of patients, consisting of local recurrence in 7% (3/46), and metastatic disease in 93% (43/46). The 3-year PFS was 67%, with a median PFS of 49 months. Of those who progressed, the median time to progression was 10.3 months. CONCLUSIONS This study is the largest cohort of pT3 RCC patients treated laparoscopically in the literature and suggests that for properly selected patients, laparoscopic management of locally advanced renal masses yields acceptable short-term oncological outcomes.

The value of a core clinical rotation in urology for medical students

INTRODUCTION In 2013, our institution underwent a change to the undergraduate medical curriculum whereby a clinical urology rotation became mandatory. In this paper, we evaluated the perceived utility and value of this change in the core curriculum. METHODS Third year medical students, required to complete a mandatory 1-week clinical urology rotation, were asked to complete a survey before and after their rotation. Fourth year medical students, not required to complete this rotation, were also asked to complete a questionnaire. Chi-squared and Fishers exact test were used for data analysis. RESULTS In total, 108 third year students rotated through urology during the study period. Of these, 66 (61%) completed the pre-rotation survey and 54 (50%) completed the post-rotation survey. In total, there were 110 fourth year students. Of these, 44 (40%) completed the questionnaire. After completing their mandatory rotations, students felt more comfortable managing and investigating common urological problems, such as hematuria and renal colic. Students felt they had a better understanding of how to insert a Foley catheter and felt comfortable independently inserting a Foley catheter. Importantly, students felt they knew when to consult urology and were also more likely to consider a career in urology. Compared to fourth year students, third year students felt urology was an important component to a family medicine practice and felt they had a better understanding of when to consult urology. CONCLUSION The introduction of a mandatory urology rotation for undergraduate medical students leads to a perceived improvement in fundamental urological knowledge and skill set of rotating students. This mandatory rotation provides a valuable experience that validates its inclusion.

Laparoscopic nephrectomy, ex vivo partial nephrectomy, and autotransplantation for the treatment of complex renal masses.

In the contemporary era of minimally invasive surgery, very few T1/T2 renal lesions are not amenable to nephron-sparing surgery. However, centrally located lesions continue to pose a clinical dilemma. We sought to describe our local experience with three cases of laparoscopic nephrectomy, ex vivo partial nephrectomy, and autotransplantation. Laparoscopic donor nephrectomy was performed followed by immediate renal cooling and perfusion with isotonic solution. Back-table partial nephrectomy, renorrhaphy, and autotransplantation were then performed. Mean warm ischemia (WIT) and cold ischemic times (CIT) were 2 and 39 minutes, respectively. Average blood loss was 267 mL. All patients preserved their renal function postoperatively. Final pathology confirmed pT1, clear cell renal cell carcinoma with negative margins in all. All are disease free at up to 39 months follow-up with stable renal function. In conclusion, the described approach remains a viable option for the treatment of complex renal masses preserving oncological control and renal function.