Kyo Chul Koo

Tumor Lesion Diameter on Diffusion Weighted Magnetic Resonance Imaging Could Help Predict Insignificant Prostate Cancer in Patients Eligible for Active Surveillance: Preliminary Analysis

PURPOSE We analyzed the pathological outcomes of candidates for active surveillance according to tumor lesion diameter on diffusion weighted magnetic resonance imaging. MATERIALS AND METHODS We retrospectively analyzed 188 candidates for active surveillance who had undergone diffusion weighted magnetic resonance imaging before radical prostatectomy between 2006 and 2012. We measured the diameter of the suspicious tumor lesion on diffusion weighted magnetic resonance imaging and stratified the cohort into 2 groups. Group 1 included patients with normal magnetic resonance imaging or a suspicious tumor lesion smaller than 1 cm and group 2 included patients with a suspicious tumor lesion larger than 1 cm. We compared pathological outcomes including insignificant prostate cancer in each group and analyzed whether different tumor diameters resulted in a change in insignificant prostate cancer rates. RESULTS Group 1 consisted of 115 (61.2%) patients and group 2 included 73 (38.8%) patients. In group 1 magnetic resonance imaging was normal in 72 patients. Mean ± SD diameter of suspicious tumor lesions was 12.0 ± 5.58 mm. Tumor volume was significantly different between the groups (0.73 ± 0.86 vs 1.09 ± 1.07 cm(3), p = 0.018), as was the rate of insignificant prostate cancer (48.7% vs 24.7%, p = 0.001). The rate of insignificant prostate cancer decreased as tumor diameter increased over 1 cm. On multivariate logistic regression analysis the diameter of suspicious tumor lesions was an important predictor of insignificant prostate cancer (OR 0.319, p = 0.014). CONCLUSIONS Our analysis demonstrates that the simple measurement of the diameter of suspicious tumor lesions on diffusion weighted magnetic resonance imaging could improve the prediction of insignificant prostate cancer in candidates for active surveillance.

Trends of Presentation and Clinical Outcome of Treated Renal Angiomyolipoma

Purpose The purpose of this study is to set guidelines for the management of renal angiomyolipoma (AML), clinical prognosis according to tumor size, in association with tuberous sclerosis complex (TSC), multiplicity, radiographic finding, and treatment modality. Materials and Methods Between March 1998 and October 2008, 129 out of 254 patients with AML who underwent surgical intervention or angioembolization were enrolled. Diagnosis of AML was determined by the presence of a low attenuated component on CT imaging or by pathological confirmation. Indications of treatment were intractable pain, hematuria, suspicion of malignancy, large tumor size, spontaneous rupture, and radiographically equivocal tumors in which a differential diagnosis was needed to rule out malignancy. Parameters including age, sex, tumor size, multiplicity, radiographic characteristics, association with TSC, and treatment modality were reviewed. Results Age at presentation was 50.6 years and mean tumor size was 3.5 cm. Presentation symptoms were flank pain, hematuria, spontaneous rupture, and fatigue. 97 (75.2%) patients were incidentally discovered. 100 (77.5%) were females. 68 (52.7%) underwent nephron-sparing surgery (NSS), 35 (27.1%) radical nephrectomy, and 26 (20.2%) angioembolization. TSC was accompanied in 12 (9.3%) patients. No patient developed renal function impairment during the mean follow-up period of 64.8 months. Patients with TSC presented at a younger age, along with larger, bilateral, and multiple lesions. Conclusion Significant differences in clinical manifestations and treatment outcomes were noted in respect to tumor characteristics, association with TSC, and treatment modality. Considering the benign nature of AML, these parameters ought to be considered when deciding upon active surveillance or prophylactic intervention.

R-LESS Partial Nephrectomy Trifecta Outcome Is Inferior to Multiport Robotic Partial Nephrectomy: Comparative Analysis

BACKGROUND Trifecta achievement in partial nephrectomy (PN) is defined as the combination of warm ischemia time ≤ 20 min, negative surgical margins, and no surgical complications. OBJECTIVE To compare trifecta achievement between robotic, laparoendoscopic, single-site (R-LESS) PN and multiport robotic PN (RPN). DESIGN, SETTING, AND PARTICIPANTS Data from 167 patients who underwent RPN from 2006 to 2012 were retrospectively analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary outcome measurement was trifecta achievement; secondary outcome was the perioperative and postoperative comparison between groups. The measurements were estimated and analyzed with SPSS v.18 using univariable, multivariable, and subgroup analyses. RESULTS AND LIMITATIONS Eighty-nine patients were treated with RPN and 78 were treated with R-LESS PN. Baseline characteristics of both groups were similar. Trifecta was achieved in 38 patients (42.7%) in the multiport RPN group and 20 patients (25.6%) in the R-LESS PN group (p=0.021). Patients in the R-LESS PN group had longer mean operative time, warm ischemia time, and increased estimated glomerular filtration rate (eGFR) percentage change. No significant differences were found between the two groups in days of hospitalization, blood loss, postoperative eGFR, positive surgical margins, and surgical complications. Patients with increased PADUA and RENAL scores, infiltration of the collecting system, and renal sinus involvement had an increased probability of not achieving the trifecta. In regression analysis, the type of procedure and the tumor size could predict trifecta accomplishment (p=0.019 and 0.043, respectively). The retrospective study, the low number of series, and the controversial definition of trifecta were the main limitations. CONCLUSIONS The trifecta was achieved in significantly more patients who underwent multiport RPN than those who underwent R-LESS PN. R-LESS PN could be an alternative option for patients with decreased tumor size, low PADUA and RENAL scores, and without renal sinus or collecting system involvement. PATIENT SUMMARY In this study, we looked at the outcomes of patients who had undergone robotic partial nephrectomy. We found that conventional robotic partial nephrectomy is superior to R-LESS partial nephrectomy with regard to the accomplishment of negative margins, reduced warm ischemia time, and minimal surgical complications.

Low-risk Prostate Cancer Patients Without Visible Tumor (T1c) On Multiparametric MRI Could Qualify for Active Surveillance Candidate Even If They Did Not Meet Inclusion Criteria of Active Surveillance Protocol

INTRODUCTION We compared the pathologic outcomes of prostate cancer patients who did not qualify for active surveillance according to the tumor visibility on multiparametric magnetic resonance imaging. MATERIAL AND METHODS We retrospectively analyzed 464 prostate cancer patients who underwent multiparametric magnetic resonance imaging before radical prostatectomy between 2006 and 2012. All the patients had clinically localized prostate cancer with Gleason score ≤6 and prostate-specific antigen ≤10 ng/ml. Of these patients, 238 were eligible for active surveillance (group A) and 226 were not. We divided these 226 patients into two groups according to the result of multiparametric magnetic resonance imaging: 59 (26.1%) patients without visible tumor (group B) and 167 (73.9%) patients with visible tumor (group C). We evaluated the pathologic outcomes of organ-confined Gleason ≤6 disease and unfavorable disease in each group. RESULTS The proportions of organ-confined Gleason ≤6 disease and unfavorable disease were 63.9 and 11.3% in group A, 59.3 and 10.2% in group B, and 38.9 and 22.8% in Group C. Comparing group A and B, these proportions were not statistically different (P = 0.549 and P = 1.000, respectively). However, comparing group A and C, those were significantly different (P < 0.001 and P = 0.002, respectively). In multivariate logistic regression analysis, no visible tumor on multiparametric magnetic resonance imaging was an independent predictor of organ-confined Gleason score 6 disease (odds ratio 0.426, P = 0.007) but there was no statistically independent predictor for unfavorable disease. CONCLUSIONS The tumor visibility on multiparametric magnetic resonance imaging could be a predictor of favorable disease for the prostate cancer patients who did not meet active surveillance criteria. Multiparametric magnetic resonance imaging could help to determine treatment modality for the low-risk prostate cancer patients who consider active surveillance even if they did not meet active surveillance criteria.

Prostatic Urethral Angulation Associated With Urinary Flow Rate and Urinary Symptom Scores in Men With Lower Urinary Tract Symptoms

OBJECTIVE To evaluate the effect of the prostatic urethral angle (PUA) on the peak flow rate (Qmax) and urinary symptoms in the clinical setting. MATERIALS AND METHODS The records were obtained from a prospectively maintained database for first-visit men with lower urinary tract symptoms. Uroflowmetric measurements, postvoid residual urine volume, and International Prostate Symptom Score were assessed. The prostate-related parameters, including prostate volume, PUA, and intravesical prostatic protrusion, were measured using transrectal ultrasonography. Patients with comorbidities that can affect voiding function or in whom the PUA could not be measured were excluded. RESULTS A total of 316 patients were included. On multivariate linear regression analysis, the PUA (P = .002) was independently associated with the International Prostate Symptom Score. However, the International Prostate Symptom Score was not influenced by patient age, prostate volume, or intravesical prostatic protrusion. The mean PUA was significantly different according to symptom severity. The mean PUA was 42.2° ± 7.0°, 45.5° ± 9.1°, and 47.3° ± 8.6° in patients with mild, moderate, and severe symptoms, respectively (P = .004, analysis of variance). Although the PUA (P <.001) and patient age (P <.001) were independent predictors of Qmax, the prostate volume and intravesical prostatic protrusion did not affect the Qmax. The mean PUA was 52.2° ± 7.3° in patients with a Qmax <10 mL/s, 45.0° ± 7.9° in those with a Qmax ≥10 mL/s but <20 mL/s, and 39.8° ± 7.9° in those with a Qmax of ≥20 mL/s (P <.001, analysis of variance). CONCLUSION The results of our study has shown that the PUA is significantly associated with the Qmax and symptom scores in men with lower urinary tract symptoms. Our findings suggest that the PUA should be considered in the treatment of male patients with lower urinary tract symptoms.

Reduction of the CD16−CD56bright NK Cell Subset Precedes NK Cell Dysfunction in Prostate Cancer

Background Natural cytotoxicity, mediated by natural killer (NK) cells plays an important role in the inhibition and elimination of malignant tumor cells. To investigate the immunoregulatory role of NK cells and their potential as diagnostic markers, NK cell activity (NKA) was analyzed in prostate cancer (PCa) patients with particular focus on NK cell subset distribution. Methods Prospective data of NKA and NK cell subset distribution patterns were measured from 51 patients initially diagnosed with PCa and 54 healthy controls. NKA was represented by IFN-γ levels after stimulation of the peripheral blood with Promoca®. To determine the distribution of NK cell subsets, PBMCs were stained with fluorochrome-conjugated monoclonal antibodies. Then, CD16+CD56dim and CD16−CD56bright cells gated on CD56+CD3− cells were analyzed using a flow-cytometer. Results NKA and the proportion of CD56bright cells were significantly lower in PCa patients compared to controls (430.9 pg/ml vs. 975.2 pg/ml and 2.3% vs. 3.8%, respectively; p<0.001). Both tended to gradually decrease according to cancer stage progression (p for trend = 0.001). A significantly higher CD56dim-to-CD56bright cell ratio was observed in PCa patients (41.8 vs. 30.3; p<0.001) along with a gradual increase according to cancer stage progression (p for trend = 0.001), implying a significant reduction of CD56bright cells in relation to the alteration of CD56dim cells. The sensitivity and the specificity of NKA regarding PCa detection were 72% and 74%, respectively (best cut-off value at 530.9 pg/ml, AUC = 0.786). Conclusions Reduction of CD56bright cells may precede NK cell dysfunction, leading to impaired cytotoxicity against PCa cells. These observations may explain one of the mechanisms behind NK cell dysfunction observed in PCa microenvironment and lend support to the development of future cancer immunotherapeutic strategies.

Efficacy of Octreotide for Management of Lymphorrhea After Pelvic Lymph Node Dissection in Radical Prostatectomy

OBJECTIVES To examine the efficacy of octreotide for management of lymphorrhea after pelvic lymph node dissection (PLND) in radical prostatectomy. Lymphorrhea refers to the drainage of lymphatic fluid that occurs because of surgical dissection and inadequate closure of afferent lymphatic vessels. METHODS We enrolled 89 patients from whom more than 200 mL of lymphorrhea had been drained at postoperative day (POD) 3 after PLND. Of the 89 patients, 45 were managed by conservative methods (untreated group) without the injection of octreotide in the earlier period, and the remaining 44 received injections of octreotide (treated group) in the later period. Octreotide was injected subcutaneously 3 times a day, starting on POD 3. Pelvic drains were removed when the total drainage per day was less than 50 mL. Octreotide was also injected for 1-2 days after drain removal. We compared mean age, prostate-specific antigen, Gleason score, daily amount of lymphorrhea, duration of drain placement, hospital stay, number of harvested lymph nodes (LNs), number of positive LNs, and complications between the 2 groups. RESULTS The mean age, prostate-specific antigen, Gleason score, amount of lymphorrhea at POD 3, number of harvested LNs, and the number of positive LNs were not significantly different between the 2 groups. Patients treated with octreotide produced significantly less lymphorrhea daily (205.7 +/- 231.3 mL in untreated group, 95.2 +/- 128.7 mL in treated group) (P <.001). The duration of drainage placement was significantly shorter in the treated group (8.9 +/- 1.9 days) than in the untreated group (12.1 +/- 3.8 days) (P <.001). The hospital stay was also significantly shorter in the treated group (9.9 +/- 3.1 days) than in the untreated group (14.9 +/- 3.9 days) (P <.001). There were no significant systemic side effects of octreotide. Lymphoceles occurred in 8 cases in the untreated group and 2 cases in the treated group. CONCLUSIONS The injection of octreotide is an effective and safe treatment for the management of lymphorrhea after PLND. Additional studies are needed to determine optimal dosage and treatment regimens.

Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels

Purpose Prostate-specific antigen (PSA) is a surrogate marker of disease progression; however, its predictive ability in the extreme ranges is unknown. We determined the predictors of survival in patients with bone metastatic prostate cancer (BMPCa) and with extremely high PSA levels. Methods Treatment-naïve patients (n = 248) diagnosed with BMPCa between December 2002 and June 2012 were retrospectively analyzed. Clinicopathological features at diagnosis, namely age, body mass index, serum alkaline phosphatase (ALP) and PSA levels, PSA nadir, time to PSA nadir and its maintenance period, PSA declining velocity, Gleason grade, clinical T stage, pain score, Eastern Cooperative Oncology Group performance score (ECOG PS), and the number of bone metastases were assessed. The patients were stratified according to PSA ranges of <20 ng/mL, 20–100 ng/mL, 100–1000 ng/mL, and 1000–10,000 ng/mL. Study endpoints were castration-resistant PCa (CRPC)-free survival and cancer-specific survival (CSS). Results Patients with higher PSA and ALP levels showed more bone lesions (P < 0.001). During the follow-up period (median, 39.9 months; interquartile range, 21.5–65.9 months), there were no differences between the groups in terms of the survival endpoints. High ALP levels, shorter time to PSA nadir, and pain were associated with an increased risk of progression to CRPC, and high ALP levels, ECOG PS ≥ 1, and higher PSA nadir independently predicted CSS. Conclusions PSA response to androgen deprivation therapy and serum ALP are reliable predictors of survival in patients with BMPCa presenting with extremely high PSA levels. These patients should not be deterred from active treatment based on baseline PSA values.

Feasibility of robot-assisted radical prostatectomy for very-high risk prostate cancer: surgical and oncological outcomes in men aged ≥70 years.

Purpose Robot-assisted radical prostatectomy with pelvic lymph node dissection (RALP-PLND) is a feasible treatment option for high-risk prostate cancer (HPCa), but remains controversial for very high-risk prostate cancer (VHPCa). We aimed to assess the feasibility of RALP-PLND in men ≥70 years with VHPCa features by comparing outcomes to those of HPCa. Methods Among patients aged ≥70 years who underwent RALP-PLND between 2005 and 2012, 101 HPCa patients (31%) (PSA≥20 ng/mL or biopsy Gleason 8–10 or cT3a) and 53 VHPCa patients (16%) (≥cT3b or cN1) were identified. Perioperative, functional, and oncological outcomes were compared between groups. Results Perioperative outcomes including operative time (P=0.917), estimated blood loss (P=0.181), and complications (P=0.239) were comparable. Due to Gleason score downgrading, 19% of HPCa and 4% of VHPCa were actually of intermediate risk. VHPCa revealed higher LN involvements (P=0.002). Discrepancy between clinical and pathological nodal status was more frequent in VHPCa (36% vs. 7%, P<0.01). Nodal metastasis would have been missed in 23% patients without PLND, while 13% of cN1 patients were shown to be metastasis-free by PLND. Continence rates were lower for VHPCa (32% vs. 56%, P=0.013). Although biochemical recurrence-free survival rates were comparable (P=0.648), risk for later adjuvant treatments was higher for VHPCa patients (14% vs. 34%, P<0.01). Conclusions RALP-PLND is a feasible option for VHPCa in elderly patients with satisfactory oncologic outcomes; however, functional outcomes were not as favorable. Patients who are unable to accept the risk of adjuvant therapy and its side effects or incontinence should be deterred from surgical treatment, and other options such as radiation therapy could be an alternative.

Prognostic Impacts of Metastatic Site and Pain on Progression to Castrate Resistance and Mortality in Patients with Metastatic Prostate Cancer.

Purpose To investigate predictors of progression to castration-resistant prostate cancer (CRPC) and cancer-specific mortality (CSM) in patients with metastatic prostate cancer (mPCa). Materials and Methods A retrospective analysis was performed on 440 consecutive treatment-naïve patients initially diagnosed with mPCa between August 2000 and June 2012. Patient age, body mass index (BMI), Gleason score, prostate-specific antigen (PSA), PSA nadir, American Joint Committee on Cancer stage, Visual Analogue Scale pain score, Eastern Cooperative Oncology Group performance score (ECOG PS), PSA response to hormone therapy, and metastatic sites were assessed. Cox-proportional hazards regression analyses were used to evaluate survivals and predictive variables of men with bone metastasis stratified according to the presence of pain, compared to men with visceral metastasis. Results Metastases were most often found in bone (75.4%), followed by lung (16.3%) and liver (8.3%) tissues. Bone metastasis, pain, and high BMI were associated with increased risks of progression to CRPC, and bone metastasis, pain, PSA nadir, and ECOG PS≥1 were significant predictors of CSM. During the median follow-up of 32.0 (interquartile range 14.7-55.9) months, patients with bone metastasis with pain and patients with both bone and visceral metastases showed the worst median progression to CRPC-free and cancer-specific survivals, followed by men with bone metastasis without pain. Patients with visceral metastasis had the best median survivals. Conclusion Metastatic spread and pain patterns confer different prognosis in patients with mPCa. Bone may serve as a crucial microenvironment in the development of CRPC and disease progression.