Myungchan Park

Predictive Characteristics of Malignant Pheochromocytoma

Purpose The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. We aimed to identify the clinical characteristics predictive of malignancy after initial surgical removal in patients with pheochromocytoma. Materials and Methods We retrospectively reviewed the records of 152 patients diagnosed with pheochromocytoma, including 5 (3.3%) with metastasis at the time of the initial surgical excision and 12 (7.9%) who developed metastasis during follow-up. To determine the factors predictive of malignancy, we compared clinical, radiographical, and urinary chemical findings between patients with benign and malignant disease. Mean follow-up was 41.5 months (range, 0.9-298 months) after surgery. Results Malignant tumors were significantly larger than benign tumors (11.1±4.0 cm vs. 6.2±3.4 cm, p<0.001), and postoperative persistence of arterial hypertension was more frequent after removal of malignant than benign tumors (p=0.001). Among the 147 patients without metastatic disease at diagnosis, those who developed metastasis had significantly lower concentrations of urinary catecholamine metabolites per unit of tumor, including vanillylmandelic acid (1.2 vs. 3.7 mg/day/cm, p=0.049), epinephrine (4.5 vs. 168.9 µg/day/cm, p=0.008), and norepinephrine (13.1 vs. 121.8 mg/day/cm, p<0.001). The overall 5-year metastasis-free survival rate was 84.4% and was significantly higher in patients with smaller tumors (≤5.5 vs. >5.5 cm; 90.6% vs. 81.2%, p=0.025) and higher 24-hour secretion of vanillylmandelic acid (>2.1 vs. ≤2.1 mg/day/cm; 94.9% vs. 70.9%, p=0.019). Conclusions Large tumor size (>5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (≤2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery.

Effect of prostate size on pathological outcome and biochemical recurrence after radical prostatectomy for prostate cancer: is it correlated with serum testosterone level?

Study Type – Prognosis (case series)
Level of Evidence 4

Does repeat biopsy affect the prognosis of patients with prostate cancer treated with radical prostatectomy? Analysis by the number of cores taken at initial biopsy

Study Type – Therapy (case series)

Bone mineral density in prostate cancer: a comparative study of patients with prostate cancer and healthy controls using propensity score matching.

OBJECTIVE To determine whether the prevalence of prostate cancer is associated with a decrease in bone mineral density (BMD) compared to a healthy control group and to identify the factors associated with osteoporosis in patients diagnosed with prostate cancer before the initiation of any kind of treatment. MATERIALS AND METHODS A retrospective study was conducted in 582 patients with prostate cancer and 2536 healthy men. Confounding variables affecting BMD, including age, serum testosterone, body mass index (BMI), diabetes mellitus, hypertension, and smoking were matched in the 2 study groups using propensity score analysis. RESULTS The propensity score model included 6 variables, and matching by propensity score yielded 502 patients in the prostate cancer group matched to 502 men in the healthy control group. On the basis of the lowest T-score available, a high prevalence of osteoporosis was found in the prostate cancer group (P = .0001). Prostate cancer was the factor correlating significantly with osteoporosis before propensity score matching (odds ratio [OR] 2.96, P <.001) and after propensity score matching (OR 3.22, P <.001). By multivariate analysis, conducted to assess the significance of each variable affecting the development of osteoporosis in patients with prostate cancer, bone metastasis was found to be an independent predictor of osteoporosis (OR 3.45, P = .002), along with BMI (continuous, OR 0.75, P <.001). CONCLUSION After controlling for variables affecting BMD, prostate cancer was a risk factor for osteoporosis. Measurement of BMD is a logical first step in the clinical strategy to avoid or minimize potential bone-related complications in men with prostate cancer, especially if they have bone metastasis and a slender stature.

MP55-11 PROGNOSTIC VALUE OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF), VEGF RECEPTOR 2, PLATELET-DERIVED GROWTH FACTOR-? (PDGF-β), AND PDGF-β RECEPTOR EXPRESSION IN PAPILLARY RENAL CELL CARCINOMA

confirmed to be malignant after pathological analysis. In the ICS subgroup, with a median follow-up of 38 months, no local recurrence or metastatic progression was reported. Analyses of RFS did not found any difference among subgroups: ICS vs. no ICS (P1⁄40.23) (Figure 1), OPN vs. RAPN (P1⁄40.91) (Figure 2). No predictive factor of ICS was found. CONCLUSIONS: Intraoperative cystic spillage is rather common regardless the surgical approach, and it does not seem to impact mid-term oncological outcomes.

PD48-02 THE EFFECT OF IMMEDIATE SECOND RESECTION OF TUMOR BED AFTER COMPLETE TRANSURETHRAL RESECTION OF BLADDER TUMOR : A COMPARATIVE STUDY USING PROPENSITY SCORE MATCHING

INTRODUCTION AND OBJECTIVES: Repeat TUR is both diagnostic and therapeutic in patients with T1 NMIBC. The depth of lamina propria invasion was shown to have the largest impact on T1 tumors prognosis. We intended to evaluate the influence of lamina propria invasion type at initial TUR on the re-staging pathology. METHODS: We reviewed from our prospectively maintained database all patients with a high-grade pT1 disease who underwent a re-staging TUR within 6 weeks at our center from January 2015 to May 2016. All pathology specimens were reviewed by a dedicated uropathologist. The characteristics of the lamina propria invasion were assessed according to the pathological report to identify focal invasion. The pathology of the second TUR was analyzed regarding the characteristics of the initial resection. RESULTS: We included 198 patients, with a median age of 70 years (interquartile range: 63-79). Muscle was present in the initial TUR specimen in 107 patients (54%). Pathology restaging was pT0 in 73 patients (37%), pTis in 44 (22%), pTa in 27 (14%), pT1 in 50 (25%) and pT2 in 4 (2%). Eighty-seven patients (44%) had tumors with minimal lamina propria invasion at initial TUR (53 specimens (27%) with focal invasion, 15 (7.6%) with superficial invasion and 19 (10%) with multifocal superficial invasion). Focal invasion was defined as few malignant cells in the lamina propria, superficial invasion as T1a and multifocal superficial invasion as multiple areas of T1a. Of the patients with minimal lamina propria invasion, residual disease was found in 20 patients (23%). However, none of those patients had T2 disease (Table 1). CONCLUSIONS: A significant number of patients with T1 tumors have residual disease at restaging TUR. This is not any different among patients with minimal lamina propria invasion. All patients with T1 tumors should undergo restaging TUR irrespective of the depth of penetration into the lamina propria.

MP58-06 THE BENEFITS OF ADJUVANT CHEMOTHERAPY AFTER RADICAL CYSTECTOMY WITH PELVIC LYMPH NODE DISSECTION IN PATIENTS WITH UROTHELIAL CARCINOMA OF BLADDER ACCORDING TO THE LYMPH NODE DENSITY ON FINAL PATHOLOGY

INTRODUCTION AND OBJECTIVES: MIBC patients who respond to cisplatin based NAC, defined as stage <ypT2 at cystectomy, exhibit a high 5 year cancer specific survival (CSS) of up to 90%. In contrast, non-responders (stage 1⁄4ypT2 at cystectomy) exhibit a worse CSS (30-40%) than cystectomy alone, highlighting the need for predictors of NAC response. Recent MIBC studies have identified a gene expression based taxonomy (basal versus luminal phenotypes) similar to that of breast cancer. We evaluated the role of such a classification using immunohistochemical stains in a NAC cohort of MIBC. METHODS: Pre-treatment tissues from a cohort of 71 NAC treated MIBC patients at our institution between 2000 and 2013 were incorporated in tissue microarray and stained for CK5/6 and GATA3 (Ventana Medical Systems, AZ). Cases were assigned as luminal or basal phenotype based on the extent (70% cut off) of tumor cells with 1⁄42+ staining intensity, Figure 1A. We limited our analysis of CSS to the 40 patient who were able to tolerate 1⁄42 doses of NAC to avoid the confounding effect of patients who were not adequately dosed. RESULTS: As expected, there was an inverse association for CK5/6 and GATA3: 77% (43/56) of strong GATA3 cases exhibited weak/negative CK5/6 staining, most consistent with the luminal phenotype, and 73% (11/15) of the GATA3 weak/negative cases exhibited strong CK5/6, most consistent with the basal phenotype (Fisher’s exact p-value 0.0003). Interestingly there was a ~ 2 fold enrichment of basal the phenotype in cases with residual MIBC following NAC, Figure 1B. CONCLUSIONS: Our results suggest a differential responsiveness to NAC for MIBC based on assignment of basal and luminal phenotypes. The current findings should be further evaluated taking P53 gene expression status into account, given previous suggestion of chemotherapy resistance in P53 intact (p53-Like) MIBC. Furthermore, comparison to IHC luminal/basal MIBC phenotypes in our cohort of cystectomy only treated patients is ongoing to help discern the prognostic vs predictive role of this classification for NAC. Source of Funding: None

Prognostic value of vascular endothelial growth factor (VEGF), VEGF receptor 2, platelet-derived growth factor-β (PDGF-β), and PDGF-β receptor expression in papillary renal cell carcinoma.

The prognostic value of the expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), platelet-derived growth factor (PDGF)-β, and PDGF receptor (PDGFR)-β in papillary renal cell carcinoma (pRCC) is unknown. A total of 145 patients, who were confirmed to have pRCC, were analyzed. Expression levels of molecular markers were assessed via immunohistochemistry. The median follow-up period for all patients was 52.0 (interquartile range, 34.5-90.5) months. Among the cohort of 145 patients, high VEGF expression was observed in 100 (69.0%) patients, whereas high expression of VEGFR2, PDGF-β, and PDGFR-β was observed in 64 (44.1%), 42 (29.0%), and 30 (20.7%) patients, respectively. Only patients with high VEGFR2 expression exhibited improved 10-year recurrence-free survival (85.3% versus 58.1%; P=.005) and cancer-specific survival (86.4% versus 70.1%; P=.014) rates compared with individuals who exhibited low expression. Multivariate analysis revealed that high VEGFR2 expression was an independent prognostic factor for recurrence (hazard ratio, 0.326; P=.006) and cancer-specific mortality (hazard ratio, 0.334; P=.046). During follow-up, 17 patients received targeted drug therapy. Patients with high VEGFR2 expression showed a better initial response (partial response, 40%; stable disease, 20%; progressive disease, 40%) than patients with low expression did (partial response, 0%; stable disease, 58.3%; progressive disease, 41.7%; P=.052). pRCC with high VEGFR2 expression seems to be associated with a better initial response to targeted drug therapy and a better prognostic outcome.

S&T-60 THE INFLUENCE OF LENGTH, GRADE, AND LOCATION OF POSITIVE SURGICAL MARGIN (PSM) ON BIOCHEMICAL RECURRENCE IN ORGAN CONFINED PROSTATE CANCER

history. Without doctor’s explanation the CRR was decreased in patients with urologic medical history. CONCLUSIONS: The RR of FVC was increased by doctor’s explanation in patients aged <50 years, without private insurance, with high school graduate or higher and without past medical history. To explain personally the necessity and the completion method of a FVC by doctor was a help to record accurately the FVC in patients aged <50 years and with urologic medical history.

MP39-10 SERUM INSULIN-LIKE GROWTH FACTOR-1 (IGF-1) WAS A VALUABLE BIOMARKER TO PREDICT THE HIGH GRADE PROSTATE CANCER IN FINAL PATHOLOGY IN PATIENTS WHO HAD LOW TO INTERMEDIATE DISEASE ON BIOPSY.

RESULTS: The meta-analysis included data from 1271 men with PSA 10-25 ng / ml of whom 316 were diagnosed with high-grade cancer (Gleason score 7) and 37% had positive digital rectal examination. Base model AUCs ranged from 0.61 to 0.74, with an overall meta-analytic estimate of 0.68 (95% CI 0.65, 0.72). In contrast, AUCs from the kallikrein panel ranged between between 0.78 to 0.89, with a meta-analytic estimate of 0.84 (95% CI 0.81, 0.86). The increment in AUC was no smaller than 0.09 in the any cohort. Focusing on the cohorts with contemporary biopsy and grading approaches, use of the panel at a typical cut-point of 7.5% would reduce the number of biopsies by 173 per 1000 men and delay the diagnosis of 6.5 high grade cancers. The risk of high-grade cancer in men deemed to be at low risk would be less than 4%, equivalent risk to a 70 year old with a PSA of 2 ng/ mL. CONCLUSIONS: The kallikrein panel retains its excellent discrimination for high grade prostate cancer in men with high PSA (1025 ng / mL). Use of the panel in this population reduces biopsy rates without missing an undue number of high-grade tumors.