Abstract Objectives Clinical outcomes in older adults with metastatic renal cell carcinoma (mRCC) are poorly understood, particularly in the era of targeted therapies. We characterize survival and ...relevant treatment-related variables in a modern series. Materials and Methods From an institutional database including 562 patients with RCC, a total of 219 patients with metastatic disease were identified for the current analysis. Survival was assessed in four age-based cohorts: (1) age < 55, (2) age 55–64, (3) age 65–74, and (4) age ≥ 75. The number of lines of therapy rendered was collected for each patient, and the reason for treatment discontinuation was characterized. Results Of the 219 patients assessed, median age was 58 (range, 26–87), and most patients had clear cell histology (82%) and prior nephrectomy (70.9%). The majority of patients were characterized as intermediate-risk (53%) by MSKCC criteria. Median survival in patients age ≥ 75 was 12.5 months, as compared to 26.4 months for patients age < 75 (P = 0.003). Patients age ≥ 75 received fewer lines of systemic therapy as compared to other age-based subsets, and more frequently discontinued therapies due to toxicity. Conclusions Older adults represent a unique subpopulation of patients with mRCC, with distinct clinical outcomes. Further research is warranted to better understand the safety and tolerability of current therapies for mRCC in this group.
We analyzed the effect of previous abdominal surgery (PAS) on consecutive patients who underwent robot-assisted radical cystectomy (RARC).
From 2005 to 2008, 73 patients at a single institution ...underwent RARC with bilateral extended pelvic lymph node dissection and urinary diversion. Lysis of adhesions was performed robotically and laparoscopically. Records were reviewed to assess the impact of PAS on operative outcomes and complications up to 3 months after surgery.
Of the 73 patients, 37 (51%) had undergone PAS. Of these 37, 6 (16%) had PAS above the umbilicus, and 31 (84%) had surgery either above and below or strictly below the umbilicus. Patients with PAS were significantly older than those without (P<0.01). No statistically significant difference was seen with respect to blood loss, transfusion requirement, operative time, lysis of adhesion time, length of ICU stay, overall hospital stay, or the need for reoperation between patients with PAS and those without PAS. The overall postoperative complication rate was higher in the group with PAS (P=0.04). Lymph node yield was higher in patients without PAS (P<0.01). Patients with PAS below the umbilicus had a significantly longer hospital stay than patients with surgery strictly above the umbilicus had (P=0.01). Whether individuals had previously undergone single or multiple surgeries had no significance.
Robot-assisted radical cystectomy in patients with a history of previous surgery may carry a higher risk for postoperative complications. However, previous operations do not appear to affect the likelihood of a safely completed robotic operation. Patients should be counseled about their risk of obstacles after surgery.
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Background: Emerging evidence has suggested that local tumor control may enhance the effect of subsequent therapies in patients with metastatic prostate cancer. However, little is ...known about surgical safety of cytoreductive prostatectomy (CRP). In this study, we report the first interim analysis of a phase I study evaluating the safety and feasibility of CRP. Methods: The study was approved by the IRB and activated in June, 2015. Individuals with newly diagnosed clinical metastatic prostate cancer to lymph node or bones (cT1-3N1M0 or cT1-3N0M1a-b) were recruited. Following surgery, all patients received androgen deprivation therapy. The primary endpoint is the major complication rate (Clavien ≥ III). The secondary outcome measures are the time to PSA nadir and rate of incontinence (pad-free). Results: A total of 20 men from two institutions have been enrolled and undergone CRP. Overall, 6 (35.3%) perioperative complications were observed, including 1 major complication (Clavien ≥ III). There were 5 minor complications, including deep venous thrombus (Clavien II), postoperative ileus (Clavien II), and 3 cases of urethral anastomotic leaks (Clavien I). In men with a minimum of 6 month follow-up, PSA < 0.2 ng/ml in 63.6% of men and 50% of men were pad free. Conclusions: CRP is surgically feasible in carefully selected patients. However, early incontinence rate is high. Further studies are warranted to further define long-term complications and verify the oncologic benefits of the surgery. Clinical trial information: NCT02458716. Table: see text
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Background: Bladder cancer is the second most common urologic malignancy with over 73,350 new cases diagnosed annually of which the incidence is increasing in the elderly. Radical ...cystectomy (RC), the gold standard for muscle invasive disease, carries a particularly high risk of morbidity and mortality, as well as a protracted length of stay (LOS) and increased readmission rates when compared with other major urologic procedures. Furthermore, in 2013, the Institute of Medicine (IOM) declared cancer care in the US a national crisis with a priority to improve quality of care through care coordination (CC). Simultaneously, enhanced recovery after surgery (ERAS) protocols have surfaced as coordinated, evidence-based models designed to standardize medical care, improve outcomes, and lower healthcare costs. At City of Hope (COH), we evaluated our ERAS and CC pathway. Methods: In April of 2014, an ERAS and CC pathway for bladder cancer was launched at COH with an emphasis on the perioperative care of patients (pts) from a multi-disciplinary team perspective. Preoperatively, pts undergo orientation on stoma education, goals of care, and treatment expectations. The pathway clinically focuses on avoidance of bowel preparation, early feeding, minimizing narcotics, and u-opioid antagonists. On discharge, pts are closely monitored via scheduled phone calls as well as clinic visits. Quality metrics including LOS, complications, and readmissions are reported as median and interquartile range along with descriptive statistics including chi-square and Wilcoxon rank-sum tests. Results: Since implementation, the median LOS was statistically significant between cohorts with 6 days for pts on pathway compared to 8 days for those preceding the pathway (p = 0.0007). Furthermore, the complication and readmission rates have decreased from 67.5% to 50% and from 35% to 30%, respectively. Dehydration and urinary tract infection (UTI) accounted for 17.9% and 21.4% of readmissions for those prior to the pathway, while UTI occurred in 5% of pts readmitted after adhering to the pathway. Conclusions: Our ERAS and CC pathway has reduced LOS without an increase in complication nor readmission rates.
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Background: Clear cell renal cell carcinoma (ccRCC) metastasis is associated with a dismal prognosis. Early identification of patients at high or low risk of metastasis may help to ...guide appropriate treatment. There are currently no reliable clinico-pathologic and laboratory modalities for this purpose in a routine clinical setting. We previously performed a microarray study using frozen ccRCC specimens and identified dysregulation of 4 microRNAs (miRNAs), miR-10b, miR-139-5p, miR-130b and miR-199b-5p, to be highly associated ccRCC metastasis and prognosis. Methods: We established a training cohort including formalin-fixed paraffin-embedded (FFPE) specimens of localized (n = 13; pT1) and metastatic (n = 15; M1) ccRCCs. We measured the expression of the 4 miRNAs of the training cohort samples by quantitative RT-PCR, normalized with miR-24, one of the most stably expressed miRNAs in human renal tissue as we previously reported. Using the risk score method, we rebuilt a mathematical formula with cutoff points to predict a patient to be at high, low or equivocal risk of metastasis. We validated the signature in an FFPE test cohort of 265-case primary ccRCCs. We examined the signature performance and its correlation with the cancer-specific survival. Results: Multivariate logistic regression analysis showed the signature to be highly associated with ccRCC metastasis (OR 7.67, 95%Cl 2.80-21.09, p < 0.0001), with the overall sensitivity and specificity of 80% and 76%. The sensitivities and specificities were 72% and 78%, 70% and 67%, and 78% and 75% for stage I, II or III patients, respectively. The signature predicted metastasis of small ccRCCs ( ≤ 4.0 cm), with the sensitivity of 60% and specificity of 77%. The overall positive and negative predictive values (PPV and NPV) were 61% and 89%. The area under the curve of ROC was 0.8. The signature was also found to be well correlated with worse cancer-specific survival (HR 3.06, 95%Cl 1.49-6.93, p < 0.01). Conclusions: This optimized miRNA signature can reliably predict ccRCC metastasis and prognosis and may help to stratify patients for more appropriate therapies and suitable clinical trials.
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Background: In preclinical models, NTPs appear to establish a pre-metastatic niche that fosters the invasion of metastases (Kowanetz et al. PNAS 2010). This observation still ...requires clinical validation in MIBC. Methods: Benign LN tissue was obtained from patients (pts) who had undergone cystectomy and LN dissection for documented MIBC. Immunohistochemical (IHC) staining for CD15 (a NTP marker) was performed. Interleukin-17 (IL-17) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3), putative mediators of NTP recruitment, were assessed through the same method (Laan et al. J Immunol 1999; Fielding et al. J Immunol 2008). Positively staining cells were counted and averaged over 8 high power fields. Pts were stratified by the median cell count for each biomarker. Analyses of overall survival (OS) were performed using the Kaplan-Meier method and log-rank test. Results: Of 55 pts with MIBC, 19 pts received no neoadjuvant chemotherapy (NAC), while 36 pts had received NAC with either GC (n=17) or MVAC (n=19). CD15 and IL-17 expression was significantly lower in pts with prior NAC (P<0.001 for both), while expression of pSTAT3 was similar in both groups. Furthermore, across the whole cohort, a strong association was seen between expression of CD15 and IL-17 (r=0.73, P<0.001). Amongst patients with no prior NAC, median OS was higher in those pts with low CD15 v high CD15 (158.7 mos v 36.9 mos, P=0.02), and low pSTAT3 v high pSTAT3 (NR v 106.4 mos, P=0.04). Median OS was numerically higher in pts with low IL-17 v high IL-17 (114.5 v 36.9 mos; P=0.14). Patients with both low CD15/IL-17 had a particularly favorable outcome. Amongst pts with prior exposure to NAC, no difference in survival was noted based on CD15, pSTAT3 or IL-17. Conclusions: NTP recruitment to benign LNs (potentially mediated by IL-17) may be prognostic of OS in pts with MIBC who have not received NAC. Bolstered by these findings, the prognostic value of NTP recruitment will be examined prospectively in SWOG 1011, a trial comparing limited v extended LN dissection in pts with MIBC.
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Background: In preclinical models, NTPs appear to establish a pre−metastatic niche that fosters the invasion of metastases (Kowanetz et al PNAS 2010). This observation still ...requires clinical validation in MIBC. Methods: Benign LN tissue was obtained from patients (pts) who had undergone cystectomy and LN dissection for documented MIBC. Immunohistochemical (IHC) staining for CD15, a NTP marker, was performed for the entire cohort. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3), vascular endothelial growth factor receptor−1 (VEGFR1), and CD68 (a macrophage marker) were further assessed in an initial cohort (detailed subsequently) via IHC. Positively staining cells were counted and averaged over 8 high power fields (hpfs). Pts were stratified by the median cell count for each biomarker. Analyses of overall survival (OS) were performed using the Kaplan−Meier method and log−rank test. Results: In an initial cohort of 19 pts who had received no neoadjuvant chemotherapy (NC), a median CD15 count of 284/hpf was noted. Median OS was higher in those pts with low CD15 as compared to high CD15 (158.7 mos v 36.9 mos, P=0.02). Median OS was also improved in those with high pSTAT3 v low pSTAT3 (not reached v 106.4 mos, P=0.04), but no difference was noted in OS in groups stratified by clinical stage, VEGFR1 staining, or CD68 staining. To determine if the prognostic value of CD15 staining was retained in pts with exposure to NC, the cohort was expanded to include an additional 36 pts who had received either preoperative GC (n=17) or MVAC (n=19) chemotherapy. In this group, no significant difference in OS was noted based using the previously applied CD15 cutoff. Conclusions: NTP recruitment to benign LNs may be prognostic of OS in pts with MIBC who have not received NC. pSTAT3, a putative mediator of NTP recruitment, may play a role in this phenomenon. VEGFR1 and CD68, which may mediate pre−metastatic niche through a different mechanism, do not predict OS in our dataset (Kaplan et al Nature 2005). Bolstered by these findings, the prognostic value of NTP recruitment will be examined prospectively in SWOG 1011, a trial comparing limited v extended LN dissection in pts with MIBC.
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Background: Technetium (Tc99m) trofolastat (USANC) is a novel urea-based small molecule SPECT radiotracer with utility in imaging overexpression of PSMA in prostate cancer (PCa). ...Unlike earlier agents targeting PSMA, this ligand is rapidly internalized and retained in tumors. We conducted an open-label, multicenter phase 2 study in the US and Europe (NCT01667536). An interim analysis was performed at approximately 50% accrual. Methods: Patients (pts) with confirmed adenocarcinoma of the prostate scheduled for RP with EPLND at high risk for disease outside of the prostate gland were eligible. High risk pts were ≥cT3 or Kattan nomogram score ≥130. Within 30 days of screening, pts required a bone scan and pelvic MRI. After enrollment, pts received trofolastat followed by whole-body planar and SPECT/CT imaging 3 to 6 hrs later. Pts then underwent RP with EPLND within 21 days. SPECT/CT images were evaluated centrally by 3 readers blinded to clinical information and compared to on-site pathology assessments using a common scoring template. The primary endpoint was the ability of trofolastat to detect PCa within the gland. Secondary endpoints included detection of extent and location within the gland, pelvic lymph nodes and comparative performance against MRI. Results: 84 pts were enrolled to date from 16 centers. Interim data is available for 54 pts. A majority (≥2/3) of SPECT/CT readers correctly identified the presence or absence of primary PCa in 51/54 (94%, 85-98 95% CI) patients including 2 true-negative cases treated with neoadjuvant enzalutamide. Sensitivity and specificity were 94% (84-98 95% CI) and 100% (34-100 95% CI) respectively. Conclusions: Based on the interim data available, trofolastat has accurately detected primary prostate carcinoma within the gland with high sensitivity and specificity in high-risk pts prior to surgery. Updated results, analyses of secondary endpoints, pelvic lymph nodes, and comparative performance vs. MRI from this ongoing study will be presented. Clinical trial information: NCT01667536. Table: see text
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