Boorjian, Stephen A.

AbstractBackgroundTo assess whether a prespecified statistical model based on the four kallikrein markers measured in blood—total, free, and intact prostate‐specific antigen (PSA), together with human kallikrein‐related peptidase 2 (hK2)—or any individual marker measured in pretreatment serum were associated with biochemical recurrence‐free (BCR) or metastasis‐free survival after radical prostatectomy (RP) in a subgroup of men with very high‐risk disease.MethodsWe identified 106 men treated at Mayo Clinic from 2004 to 2008 with pathological Gleason grade group 4 to 5 or seminal vesicle invasion at RP. Univariable and multivariable Cox models were used to test the association between standard predictors (Kattan nomogram and GPSM [Gleason, PSA, seminal vesicle and margin status] score), kallikrein panel, and individual kallikrein markers with the outcomes.ResultsBCR and metastasis occurred in 67 and 30 patients, respectively. The median follow‐up for patients who did not develop a BCR was 10.3 years (interquartile range = 8.2‐11.8). In this high‐risk group, neither Kattan risk, GPSM score, or the kallikrein panel model was associated with either outcome. However, after adjusting for Kattan risk and GPSM score, separately, preoperative intact PSA was associated with both outcomes while hK2 was associated with metastasis‐free survival.ConclusionsConventional risk prediction tools were poor discriminators for risk of adverse outcomes after RP (Kattan risk and GPSM risk) in patients with very high‐risk disease. Further studies are needed to define the role of individual kallikrein marker forms in the blood to predict adverse prostate cancer outcomes after RP in this high‐risk setting.

Background: To assess the differential effect of robotic assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) on survival outcomes in matched analyses performed on a large multicentric cohort. Methods: The study included 9757 patients with urothelial bladder cancer (BCa) treated in a consecutive manner at each of 25 institutions. All patients underwent radical cystectomy with bilateral pelvic lymphadenectomy. To adjust for potential selection bias, propensity score matching 2:1 was performed with two ORC patients matched to one RARC patient. The propensity-matched cohort included 1374 patients. Multivariable competing risk analyses accounting for death of other causes, tested association of surgical technique with recurrence and cancer specific mortality (CSM), before and after propensity score matching. Results: Overall, 767 (7.8%) patients underwent RARC and 8990 (92.2%) ORC. The median follow-up before and after propensity matching was 81 and 102 months, respectively. In the overall population, the 3-year recurrence rates and CSM were 37% vs. 26% and 34% vs. 24% for ORC vs. RARC (all p values > 0.1), respectively. On multivariable Cox regression analyses, RARC and ORC had similar recurrence and CSM rates before and after matching (all p values > 0.1). Conclusions: Patients treated with RARC and ORC have similar survival outcomes. This data is helpful in consulting patients until long term survival outcomes of level one evidence is available.

617 Background: Anxiety and depression are psychosocial factors which have been demonstrated to have mixed interactions with mortality across various malignancies. While these variables have been associated with poor overall survival for patients with metastatic RCC, the influence on outcomes for localized RCC has been poorly studied. We evaluated the association of anxiety or depression with survival in patients with surgically treated localized clear cell RCC (ccRCC). Methods: We performed retrospective review of our institutional nephrectomy registry to identify 1,990 patients who underwent radical or partial nephrectomy for unilateral, sporadic, non-metastatic ccRCC between 1995- 2011. Baseline anxiety and depression were identified using ICD-9 codes. Associations of anxiety or depression with outcomes of interest were evaluated using Cox proportional hazards models. Two propensity score (PS) techniques were used: adjusting for PS quintile and re-weighting by stabilized inverse probability weights. Results: A total of 197 (10%) patients had diagnoses of anxiety or depression (57 had anxiety alone, 107 had depression alone, and 33 had both anxiety and depression). Median follow-up among survivors was 10.0 (IQR 7.3-13.6) years, during which time 864 died, including 363 from RCC. Patients with anxiety or depression were younger (mean age 59 vs 62 years, p < 0.001) and had more recent operations (75% vs 47% in 2005-2011, p < 0.001) compared to those with neither diagnosis. After PS adjustment, all clinical and pathologic features were well balanced between groups. After PS adjustment, there were no significant differences in time to local ipsilateral recurrence, distant metastases, and death from RCC between groups. We did note a trend to poorer overall survival in patients with anxiety or depression (HR 1.29, 95%CI = 0.98-1.69, p = 0.065). Conclusions: Our results suggest that neither anxiety nor depression is significantly associated with oncologic outcomes among patients with localized surgically treated ccRCC. The trend toward worse overall survival among patients with anxiety or depression warrants further investigation.

560 Background: Level I evidence exists demonstrating the efficacy of the mTOR inhibitor everolimus (EVE) in decreasing tumor volume of syndromic angiomyolipomas (AMLs) among patients with Tuberous Sclerosis. No prospective data are available regarding the effect of mTOR inhibition on growth kinetics in patients with sporadic AMLs. Methods: We conducted a multi-institutional, prospective, phase 2 trial with an optimal two-stage Simon design in patients presenting with > 3cm sporadic AMLs who were candidates for surgical or percutaneous intervention. Response was defined as ≥25% volumetric reduction of the AML. Planned enrollment was 43 patients to test the null hypothesis at a 5% level of significance with 80% power. Baseline, 4- and 6-month volumetric analysis was performed by dynamic contrast-enhanced MRI (DCE-MRI). Patients received EVE 10mg for four 28-day cycles, at which point EVE was discontinued in those with < 25% volumetric reduction. Those with ≥ 25% volumetric reduction received two additional cycles of EVE. Dose reductions and interruptions were allowed to 5 mg QOD. Conservative stopping rules were established for toxicity, given the benign nature of AMLs. Results: The early stopping rules for both efficacy and toxicity were invoked. We enrolled 20 patients (median age = 68) from 5 centers with 21 sporadic AMLs. 11/20 (55%) patients completed 4 cycles of EVE, while 7/20 (35%) completed 6 cycles. Median days on treatment was 88 (2 cycles). 4/20 (20%) patients were withdrawn due to toxicity, while 8/20 (40%) withdrew due to personal preference. Dose reductions were required in 6/20 (30%) patients, and 5/20 (25%) patients had grade 3 toxicities which resolved upon discontinuation or dose reduction of EVE. At 4-month MRI, 10/16 (62.5%) patients had a ≥25% reduction in volume (mean = 54.1% decrease). At 6-month MRI, 8/12 (66.6%) patients had a ≥25% reduction in volume (mean = 51.5% decrease). Conclusions: EVE was effective in reducing tumor volume in patients with sporadic AMLs but was associated with a high rate of treatment termination due to patient preference or prespecified AEs. Neoadjuvant EVE may be useful in potentiating surgical resection of large or anatomically complex AMLs. Clinical trial information: NCT02539459.