A Proposal for Standardization of Early Outcomes Following Robot-Assisted Radical Cystectomy (RARC): RARC Tetrafecta.

BACKGROUND: Currently, there is no dedicated tool to record the early outcomes of robot-assisted radical cystectomy (RARC), and existing criteria for longer-term outcomes require a minimum of 3 months for assessment. However, early evaluation is essential to prevent future morbidity and mortality, especially in surgeries with a high risk of complications in the short term. We propose a comprehensive approach to report early RARC outcomes and investigate the influence of surgeon experience on these results. PATIENTS AND METHODS: We retrospectively analyzed the outcomes of patients who underwent RARC for bladder cancer between April 2009 and April 2020. The cohort was divided chronologically into three groups: patients 1-60 in group 1, 61-120 in group 2, and 121-192 in group 3. Patients with yields of ≥ 16 lymph nodes (LN), negative soft tissue surgical margins, absence of transfusion, and absence of major complications at 30 days were regarded as attaining the RARC tetrafecta. RESULTS: Of the 192 included patients, 93 (48.4%) achieved RARC tetrafecta, with the proportion increasing with surgical experience from 41.7% in group 1 to 55.6% in group 3. Age [odds ratio (OR) 0.947; 95% confidence interval (CI) 0.924-0.970; P = 0.021], LN yield (OR 1.432; 95% CI 1.139-1.867; P = 0.001), and greater surgical experience with RARC (> 120 patients; OR 2.740; 95% CI 1.231-6.100; P = 0.014) were significantly associated with the achievement of RARC tetrafecta. CONCLUSIONS: RARC tetrafecta could be a comprehensive method for reporting early outcomes in patients undergoing RARC, with improvements aligned with the surgeon's experience.

Rate of benign histology after resection of suspected renal cell carcinoma: multicenter comparison between Korea and the United States.

BACKGROUND: In the United States, the rate of benign histology among resected renal tumors suspected to be malignant is increasing. We evaluated the rates in the Republic of Korea and assessed the racial effect using recent multi-institutional Korean-United States data. METHODS: We conducted a multi-institutional retrospective study of 11,529 patients (8,812 from The Republic of Korea and 2,717 from the United States) and compared the rates of benign histology between the two countries. To evaluate the racial effect, we divided the patients into Korean, Asian in the US, and Non-Asian in the US. RESULTS: The rates of benign histology and small renal masses in Korean patients were significantly lower than that in United States patients (6.3% vs. 14.3%, p < 0.001) and (≤ 4 cm, 7.6% vs. 19.5%, p < 0.001), respectively. Women, incidentaloma, partial nephrectomy, minimally invasive surgery, and recent surgery were associated with a higher rate of benign histology than others. CONCLUSIONS: In Korea, the rate of benign histology among resected renal tumors was significantly lower than that in the United States. This disparity could be caused by environmental or cultural differences rather than racial differences. Our findings suggest that re-evaluating current context-specific standards of care is necessary to avoid overtreatment.

Retrospective Multicenter Analysis of Prognostic Risk Factors for One Year Recurrence in Patient With Renal Cell Carcinoma After Partial or Radical Nephrectomy: Results of Korean Renal Cancer Study Group (KRoCS) Database.

BACKGROUND: We sought to identify prognostic risk factors for one year recurrence in patient with renal cell carcinoma (RCC) after partial or radical nephrectomy. METHODS: We performed a retrospective study of 1,269 patients with RCC after partial or radical nephrectomy and diagnosed recurrence using Korean Renal Cancer Study Group (KRoCS) database between January 1991 and March 2017. Recurrence-free survival (RFS), and overall survival (OS) were calculated using the Kaplan-Meier method and multivariate Cox regression analysis were performed to evaluate independent prognostic factors for recurrence. RESULTS: The median patient age was 56 years and median follow-up period was 67 months. Multivariable analysis demonstrated BMI greater than or equal to 23 and less than 30 (vs. BMI less than 23, hazard ratio [HR]: 0.707, P = 0.020) reduced recurrence one year postoperatively. Eastern Cooperative Oncology Group performance status (ECOG PS) greater than or equal to 1 (vs. ECOG PS 0, HR: 1.548, P = 0.007), high pathological T stage (pT2 vs. pT1, HR: 2.622, P < 0.001; pT3 vs. pT1, HR: 4.256, P < 0.001; pT4 vs. pT1, HR: 4.558, P < 0.001), and tumor necrosis (vs. no tumor necrosis, HR: 2.822, P < 0.001) were independent predictive factors for early recurrence within one year in patients with RCC. Statistically significant differences on RFS and OS were found among pathological T stages (pT2 vs. pT1; pT3 vs. pT1; pT4 vs. pT1, all P < 0.001). CONCLUSION: This large multicenter study demonstrated ECOG PS greater than or equal to 1, high pathological T stage, tumor necrosis and BMI less than 23 were significant prognostic risk factors of early recurrence within one year in patients with RCC who underwent nephrectomy.

Sextant Systematic Biopsy Versus Extended 12-Core Systematic Biopsy in Combined Biopsy for Prostate Cancer.

BACKGROUND: This study assessed the comparative effectiveness of sextant and extended 12-core systematic biopsy within combined biopsy for the detection of prostate cancer. METHODS: Patients who underwent combined biopsy targeting lesions with a Prostate Imaging Reporting and Data System (PI-RADS) score of 3-5 were assessed. Two specialists performed all combined cognitive biopsies. Both specialists performed target biopsies with five or more cores. One performed sextant systematic biopsies, and the other performed extended 12-core systematic biopsies. A total of 550 patients were analyzed. RESULTS: Cases requiring systematic biopsy in combined biopsy exhibited a significant association with age ≥ 65 years (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.25-4.32; P = 0.008), PI-RADS score (OR, 2.32; 95% CI, 1.25-4.32; P = 0.008), and the number of systematic biopsy cores (OR, 3.69; 95% CI, 2.11-6.44; P < 0.001). In patients with an index lesion of PI-RADS 4, an extended 12-core systematic biopsy was required (target-negative/systematic-positive or a greater Gleason score in the systematic biopsy than in the targeted biopsy) (P < 0.001). CONCLUSION: During combined biopsy for prostate cancer in patients with PI-RADS 3 or 5, sextant systematic biopsy should be recommended over extended 12-core systematic biopsy when an effective targeted biopsy is performed.

Fat Loss in Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors.

The purpose of this study was to determine the prognostic impact of fat loss after immune checkpoint inhibitor (ICI) treatment in patients with metastatic clear cell renal cell carcinoma (ccRCC). Data from 60 patients treated with ICI therapy for metastatic ccRCC were retrospectively analyzed. Changes in cross-sectional areas of subcutaneous fat (SF) between the pre-treatment and post-treatment abdominal computed tomography (CT) images were expressed as percentages and were divided by the interval between the CT scans to calculate ΔSF (%/month). SF loss was defined as ΔSF < -5%/month. Survival analyses for overall survival (OS) and progression-free survival (PFS) were performed. Patients with SF loss had shorter OS (median, 9.5 months vs. not reached; p < 0.001) and PFS (median, 2.6 months vs. 33.5 months; p < 0.001) than patients without SF loss. ΔSF was independently associated with OS (adjusted hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.07-2.07; p = 0.020) and PFS (adjusted HR, 1.57; 95% CI, 1.17-2.12; p = 0.003), with a 5%/month decrease in SF increasing the risk of death and progression by 49% and 57%, respectively. In conclusion, Loss of SF after treatment initiation is a significant and independent poor prognostic factor for OS and PFS in patients with metastatic ccRCC who receive ICI therapy.

Cabozantinib-Loaded PLGA Nanoparticles: A Potential Adjuvant Strategy for Surgically Resected High-Risk Non-Metastatic Renal Cell Carcinoma.

Patients with high-risk non-metastatic renal cell carcinoma (RCC) are at risk of metastatic relapse following nephrectomy. Cabozantinib (CZ), a potent multitarget tyrosine kinase inhibitor, interferes with angiogenesis and immunosuppression associated with surgery-induced metastasis. Here, we explored the therapeutic potential of CZ-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CZ-PLGA-NPs) as an adjuvant strategy for targeting post-nephrectomy metastasis. A clinically relevant subline recapitulating post-nephrectomy lung metastasis of high-risk human RCC, namely Renca-SRLu5-Luc, was established through in vivo serial selection of luciferase-expressing murine RCC Renca-Luc cells. CZ was encapsulated into PLGA-NPs via the conventional single emulsion technique. The multifaceted preclinical antimetastatic efficacy of CZ-PLGA-NPs was assessed in Renca-SRLu5-Luc cells. CZ-PLGA-NPs with a smooth surface displayed desirable physicochemical properties, good CZ encapsulation efficiency, as well as controlled and sustained CZ release. CZ-PLGA-NPs exhibited remarkable dose-dependent toxicity against Renca-SRLu5-Luc cells by inducing G2/M cell cycle arrest and apoptosis. CZ-PLGA-NPs attenuated in vitro colony formation, migration, and invasion by abrogating AKT and ERK1/2 activation. An intravenous injection of CZ-PLGA-NPs markedly reduced lung metastatic burden and prolonged lifespan with favorable safety in the Renca-SRLu5-Luc experimental lung metastasis model. The novel CZ-PLGA-NPs system with multifaceted antimetastatic effects and alleviating off-target toxicity potential is a promising adjunctive agent for patients with surgically resected high-risk RCC.

Renal Cell Carcinoma-Infiltrating CD3low Vγ9Vδ1 T Cells Represent Potentially Novel Anti-Tumor Immune Players.

Due to the highly immunogenic nature of renal cell carcinoma (RCC), the tumor microenvironment (TME) is enriched with various innate and adaptive immune subsets. In particular, gamma-delta (γδ) T cells can act as potent attractive mediators of adoptive cell transfer immunotherapy because of their unique properties such as non-reliance on major histocompatibility complex expression, their ability to infiltrate human tumors and recognize tumor antigens, relative insensitivity to immune checkpoint molecules, and broad tumor cytotoxicity. Therefore, it is now critical to better characterize human γδ T-cell subsets and their mechanisms in RCCs, especially the stage of differentiation. In this study, we aimed to identify γδ T cells that might have adaptive responses against RCC progression. We characterized γδ T cells in peripheral blood and tumor-infiltrating lymphocytes (TILs) in freshly resected tumor specimens from 20 RCC patients. Furthermore, we performed a gene set enrichment analysis on RNA-sequencing data from The Cancer Genome Atlas (TCGA) derived from normal kidneys and RCC tumors to ascertain the association between γδ T-cell infiltration and anti-cancer immune activity. Notably, RCC-infiltrating CD3low Vγ9Vδ1 T cells with a terminally differentiated effector memory phenotype with up-regulated activation/exhaustion molecules were newly detected as predominant TILs, and the cytotoxic activity of these cells against RCC was confirmed in vitro. In an additional analysis of the TCGA RCC dataset, γδ T-cell enrichment scores correlated strongly with those for CTLs, Th1 cells, "exhausted" T cells, and M1 macrophages, suggesting active involvement of γδ T cells in anti-tumor rather than pro-tumor activity, and Vδ1 cells were more abundant than Vδ2 or Vδ3 cells in RCC tumor samples. Thus, we posit that Vγ9Vδ1 T cells may represent an excellent candidate for adoptive immunotherapy in RCC patients with a high risk of relapse after surgery.

A prospective phase-II trial of biweekly docetaxel plus androgen deprivation therapy in patients with previously-untreated metastatic castration-naïve prostate cancer.

INTRODUCTION: The aim of this prospective phase II study was to evaluate the efficacy and safety of biweekly docetaxel plus androgen-deprivation therapy (ADT) in patients with metastatic castration-naïve prostate cancer (mCNPC). PATIENTS AND METHODS: Patients with histologically-proven, previously-untreated mCNPC received ADT plus docetaxel, 40 mg/m2. Docetaxel was repeated every 2 weeks, up to 12 cycles. Endpoints included castration-resistant prostate cancer (CRPC)-free survival, prostate-specific antigen (PSA) response, and safety. RESULTS: A total of 42 patients were registered and analyzed for final outcomes. Of the 42 patients, 36 (86%) completed the 12 planned cycles of docetaxel plus ADT. During a median follow up of 25 months, all but two patients (95%) achieved a PSA response with a nadir PSA level of 0.42 ng/ml (range 0.01-1280.87). The median CRPC-free survival was 26.4 months (95% confidence interval [CI] 20.9-32.0) with a one-year CRPC-free rate of 79% (33 patients, 95% CI 66-91). Multivariable analysis revealed that the performance status of the Eastern Cooperative Oncology Group 0 was independently associated with longer CRPC-free survival (hazard ratio [HR] 0.27, 95% CI 0.07-0.99). The most common adverse events of any grade were anemia (95%), followed by nail changes (33%), fatigue (29%), and oral mucositis (26%). Severe (grade 3 or higher) adverse events were infrequent: pneumonitis (n = 2), diarrhea (n = 1), and neutropenia (n = 1). CONCLUSION: Our results suggest that biweekly docetaxel plus ADT is feasible, and clinical efficacy does not seem to be compromised compared to a standard triweekly docetaxel 75 mg/m2 plus ADT regimen.

Targeted therapy response in early versus late recurrence of renal cell carcinoma after surgical treatment: A propensity score-matched study using the Korean Renal Cancer Study Group database.

OBJECTIVES: To investigate the clinicopathological features and outcomes of targeted therapy in patients with recurrence of renal cell carcinoma in <5 years or ≥5 years after the surgical treatment for renal cell carcinoma. METHODS: Patients with metastatic renal cell carcinoma treated with targeted therapy in a multicenter database were retrospectively characterized according to time from surgery to recurrence. Early recurrence was defined as recurrence within 5 years after surgery, and late recurrence was defined as occurring ≥5 years after surgery. The propensity scores for recurrence status were calculated, and patients with late recurrence were matched to patients with early recurrence at a 1:3 ratio. The oncological outcomes of targeted therapy in both groups were compared. RESULTS: Among 716 patients, 512 (71.5%) experienced early recurrence and 204 (28.5%) experienced late recurrence. The patients with late recurrence presented with younger age at surgery, lower tumor stages and Fuhrman grade, and fewer sarcomatoid features and lymphovascular invasion (all P < 0.005). All differences in clinicopathological characteristics before targeted therapy disappeared after matching. Patients with late recurrence had significantly longer median overall survival (56 months vs 36 months; P < 0.0001) and median first-line progression-free survival (12 months vs 8 months; P = 0.031). The early recurrence status was a significantly worse predictor for overall survival and first-line progression-free survival (hazard ratio 1.30, P = 0.007; and hazard ratio 1.76, P < 0.001, respectively). CONCLUSIONS: Late recurrence might have prognostic value in terms of oncological outcomes in metastatic renal cell carcinoma treated with targeted therapy.

Functions of human liver CD69+CD103-CD8+ T cells depend on HIF-2α activity in healthy and pathologic livers.

BACKGROUND & AIMS: Human liver CD69+CD8+ T cells are ~95% CD103- and ~5% CD103+. Although CD69+CD103+CD8+ T cells show tissue residency and robustly respond to antigens, CD69+CD103-CD8+ T cells are not yet well understood. METHODS: Liver perfusate and paired peripheral blood were collected from healthy living donors and recipients with cirrhosis during liver transplantation. Liver tissues were obtained from patients with acute hepatitis A. Phenotypic and functional analyses were performed by flow cytometry. Gene expression profiles were determined by microarray and quantitative reverse transcription PCR. PT-2385 was used to inhibit hypoxia-inducible factor (HIF)-2α. RESULTS: Human liver CD69+CD103-CD8+ T cells exhibited HIF-2α upregulation with a phenotype of tissue residency and terminal differentiation. CD103- cells comprised non-hepatotropic virus-specific T cells as well as hepatotropic virus-specific T cells, but CD103+ cells exhibited only hepatotropic virus specificity. Although CD103- cells were weaker effectors on a per cell basis than CD103+ cells, following T cell receptor or interleukin-15 stimulation, they remained the major CD69+CD8+ effector population in the liver, surviving with less cell death. An HIF-2α inhibitor suppressed the effector functions and survival of CD69+CD103-CD8+ T cells. In addition, HIF-2α expression in liver CD69+CD103-CD8+ T cells was significantly increased in patients with acute hepatitis A or cirrhosis. CONCLUSIONS: Liver CD69+CD103-CD8+ T cells are tissue resident and terminally differentiated, and their effector functions depend on HIF-2α. Furthermore, activation of liver CD69+CD103-CD8+ T cells with HIF-2α upregulation is observed during liver pathology. LAY SUMMARY: The immunologic characteristics and the role of CD69+CD103-CD8+ T cells, which are a major population of human liver CD8+ T cells, remain unknown. Our study shows that these T cells have a terminally differentiated tissue-resident phenotype, and their effector functions depend on a transcription factor, HIF-2α. Furthermore, these T cells were activated and expressed higher levels of HIF-2α in liver pathologies, suggesting that they play an important role in immune responses in liver tissues and the pathogenesis of human liver disease.

Strategy for Prostate Cancer Patients with Low Prostate Specific Antigen Level (2.5 to 4.0 ng/mL).

BACKGROUND: To evaluate the strategy for detection of prostate cancer (PCa) with low prostate specific antigen (PSA) level (2.5-4.0 ng/mL), prostate biopsy patients with low PSA were assessed. We evaluated the risk of low PSA PCa and the strategy for screening low-PSA patients. METHODS: We retrospectively analyzed the patients who underwent prostate biopsy with low PSA level. Baseline characteristics, PSA level before prostate biopsy, prostate volume, prostate specific antigen density (PSAD), and pathological data were assessed. RESULTS: Among the 1986 patients, 24.97% were diagnosed with PCa. The PSAD was 0.12 ± 0.04 ng/mL² in the PCa-diagnosed group and 0.10 ± 0.04 ng/mL² in non-cancer-diagnosed group (P < 0.001). Of the 496 patients diagnosed with PCa, 302 (60.89%) were in the intermediate- or high-risk group. PSAD was 0.13 ± 0.04 ng/mL² in the intermediate- or high-risk group and 0.11 ± 0.03 ng/mL² in the very low- and low-risk group (P < 0.001). Of 330 patients who underwent radical prostatectomy, 85.15% were diagnosed as having significant cancer. There was significant correlation between PSAD and PCa (r = 0.294, P < 0.001). PSAD with a specificity of 80.00% of a clinically significant cancer diagnosis was assessed at 0.1226 ng/mL². CONCLUSION: The PCa detection rate in the low-PSA group was not lower than that of previous studies of patients with PSA from 4.0 to 10.0 ng/mL. Further, it may be helpful to define a strategy for PCa detection using PSAD in the low-PSA group.

A randomized, double-blind, placebo-controlled trial to evaluate the role of curcumin in prostate cancer patients with intermittent androgen deprivation.

BACKGROUND: The anti-cancer activities of curcumin are well-documented from preclinical studies using prostate cancer models. Our objective was to evaluate the anti-cancer activity of oral curcumin in patients with prostate cancer. METHODS: This randomized, double-blind, placebo-controlled trial was performed on patients with prostate cancer who received intermittent androgen deprivation (IAD). Participants who finished the first on-treatment period of IAD were randomized into a curcumin or placebo group. The patients took oral curcumin (1440 mg/day) or placebo for six months and were followed up until the beginning of the second on-treatment. The primary end-point was duration of the first off-treatment. The secondary end-points were change in PSA and testosterone levels during 6 months, PSA progression rate, and health-related quality of life (HRQOL) scores at 6 months. Safety assessments included adverse event, adverse drug reaction, and serious adverse event. RESULTS: A total of 97 participants were randomized 1:1 to curcumin (n = 49) and placebo (n = 48) groups. Among them, 82 patients (84.5%) were evaluable for the analysis (39 and 43 patients in the curcumin and placebo groups, respectively). The median off-treatment duration was 16.3 months (95% confidence interval [CI] 12.3-20.3 months) and 18.5 months (95% CI 12.5-23.0 months) in the curcumin and placebo groups, respectively. There was no significant difference in the curve of off-treatment duration between the two groups (P = 0.4816). The proportion of patients with PSA progression during the active curcumin treatment period (6 months) was significantly lower in the curcumin group than the placebo group (10.3% vs 30.2%, P = 0.0259). The change of PSA, testosterone levels during 6 months, and HRQOL scores at 6 months were not different between curcumin and placebo groups. Adverse events were higher in the placebo group (16 of 46 vs 7 of 45 patients, P = 0.0349). No significant differences in the adverse drug reaction were found between the two groups. CONCLUSIONS: Six months' intake of oral curcumin did not significantly affect the overall off-treatment duration of IAD. However, PSA elevation was suppressed with curcumin intake during the curcumin administration period. Curcumin at this dose was well tolerated and safe.

Is Primary Androgen Deprivation Therapy a Suitable Option for Asian Patients With Prostate Cancer Compared With Radical Prostatectomy?

BACKGROUND: We conducted a comparative survival analysis between primary androgen deprivation therapy (PADT) and radical prostatectomy (RP) based on nationwide Korean population data that included all patients with prostate cancer. MATERIALS AND METHODS: This study enrolled 4,538 patients with prostate cancer from the National Health Insurance Service (NHIS) database linked with Korean Central Cancer Registry data who were treated with PADT or RP between January 1, 2007, and December 31, 2014. Kaplan-Meier and multivariate survival analyses stratified by stage (localized and locally advanced) and age (<75 and ≥75 years) were performed using a Cox proportional hazards model to evaluate treatment effects. RESULTS: Among 18,403 patients from the NHIS database diagnosed with prostate cancer during the study period, 4,538 satisfied inclusion criteria and were included in the analyses. Of these, 3,136 and 1,402 patients underwent RP or received PADT, respectively. Risk of death was significantly increased for patients who received PADT compared with those who underwent RP in the propensity score-matched cohort. In subgroup analyses stratified by stage and age, in every subgroup, patients who received PADT had a significantly increased risk of death compared with those who underwent RP. In particular, a much greater risk was observed for patients with locally advanced prostate cancer. CONCLUSIONS: Based on a nationwide survival analysis of nonmetastatic prostate cancer, this study provides valuable clinical implications that favor RP over PDAT for treatment of Asian populations. However, the possibility that survival differences have been overestimated due to not accounting for potential confounding characteristics must be considered.

Combination of multiparametric magnetic resonance imaging and transrectal ultrasound-guided prostate biopsies is not enough for identifying patients eligible for hemiablative focal therapy for prostate cancer.

PURPOSE: To evaluate focal therapy (hemiablation) eligibility in men undergoing prostate biopsy and multiparametric magnetic resonance imaging (mpMRI) with reference to histopathology from radical prostatectomy (RP) specimens. METHODS: Subjects were selected among 810 men who underwent prostate biopsy, mpMRI, and RP from January 2016 to December 2017. Hemiablation eligibility criteria were biopsy-proven unilateral cancer, prostate-specific antigen ≤ 15 ng/ml, and Gleason score (GS) ≤ 3 + 4. Evidence of non-organ-confined disease or Prostate Imaging Reporting and Data System score ≥ 4 on the contralateral lobe on mpMRI was classified as ineligible for hemiablation. Of the 810, data for 185 who met the screening criteria were compared to final pathology findings. Significant cancer at RP was defined as any of the following: (1) GS 6 with tumor volume ≥ 0.5 ml; (2) GS ≥ 3 + 4; or (3) the presence of advanced stage (≥ pT3). RESULTS: Among the 185 candidates for hemiablation, 62 (33.5%) had unilateral cancer on final RP histopathology. Among the 123 bilateral cancers, 50 (27%) were organ confined and had GS ≤ 3 + 4 = 7 and bilateral multifocal tumor in which the index tumor was confined to one lobe and the secondary tumor in the contralateral lobe had tumor volume < 0.5 ml and GS ≤ 6. A total of 112 (60.5%) patients in this series were considered suitable for hemiablation. Significant cancer on biopsy and mpMRI-negative lobes were found in 72 (38.9%) of 185 lobes, including 1 (0.5%) with advanced stage. CONCLUSIONS: The combination of standard prostate biopsy and mpMRI did not accurately identify lobes that could be considered as non-treated regions.

A retrospective feasibility study of biweekly docetaxel in patients with high-risk metastatic castration-naïve prostate cancer.

BACKGROUND: Results from randomized phase III trials have shown that thrice-weekly docetaxel added to androgen-deprivation therapy (ADT) has a significant impact on the survival of patients with metastatic castration-naïve prostate cancer (mCNPC) and established early chemotherapy as part of the standard of care for high-risk disease. Controversy remains, however, because some patients experience critical toxicities related to docetaxel. The purpose of the current study was to evaluate the feasibility and adverse events of biweekly-administered docetaxel in patients with previously-untreated, high-risk mCNPC. METHODS: The study included 35 consecutive patients with high-risk mCNPC who received ADT plus docetaxel 40 mg/m2. Oral prednisone 5 mg twice daily was also given. Treatment was repeated every two weeks for up to 12 cycles or until disease progression or unacceptable toxicity occurred. High-risk was defined as bone metastases beyond axial skeleton and/or visceral disease. RESULTS: The included patients' median age was 68 years (range: 31-86 years) and 17 (49%) had visceral metastases. Biweekly docetaxel was generally well-tolerated; the most commonly observed adverse events, considering those of all grades, included alopecia (74%), nail changes (42%), and constipation (31%). Hematologic adverse events were infrequent, and no patient received hematopoietic growth factors. One patient died after the fourth cycle due to respiratory failure, which occurred as a complication of pneumonia. Among the 35 patients, 28 completed the planned 12 cycles of biweekly docetaxel. Prostate-specific antigen response (> 50% decrease from baseline) was recorded in 33 patients (94%), and the radiologic response rate was 49%. Median progression-free survival was 13.6 months (95% confidence interval: 6.7-20.4). CONCLUSION: ADT plus biweekly-administered docetaxel appeared to be tolerated and effective in patients with high-risk mCNPC.

Cancer Location in Upgrading and Detection after Transperineal Template-Guided Mapping Biopsy for Patients in Active Surveillance and Negative Transrectal Ultrasonography-Guided Prostate Biopsy.

OBJECTIVES: We investigated the efficacy of transperineal template-guided mapping biopsy (TTMB) for patients on active surveillance (AS) or those with previous negative transrectal ultrasound-guided biopsy (TRUS-Bx). METHODS: We retrospectively analyzed 99 patients on AS and 60 patients with previous negative TRUS-Bx, which is a total of 159 patients who underwent TTMB from May 2017 to January 2019. Cancer location was analyzed with focus on the anterior and apex lesions of the prostate after TTMB. Multiparametric magnetic resonance imaging was performed before TTMB. Cancer location after TTMB in 138 patients, excluding 21 patients who were not eligible for analysis (4 patients on AS and 17 patients with previous negative TRUS-Bx) was compared with Prostate Imaging-Reporting and Data System version 2 (PI-RADSTM v2) score. Factors that may affect detecting cancer after TTMB with previous negative TRUS-Bx was analyzed using a logistic regression model. RESULTS: In AS patients, 29 patients (29.3%) exhibited an upgrade in Gleason score (GS) after TTMB. Among them, 22 patients (75.9%) showed at the anterior or apex lesions. In patients with previous negative TRUS-Bx, 18 patients (30.0%) were diagnosed with prostate cancer. Among them, 13 patients (72.2%) exhibited cancer at the anterior or apex lesion. Among the 25 AS patients with PI-RADSTM score 1-2, 5 patients (20.0%) showed an upgrade in GS. Among the 26 patients with previous negative TRUS-Bx and PI-RADSTM score 1-2, 6 patients (23.1%) had cancer. In multivariate regression model, prostate volume (OR 0.951) was identified as the predictor for a positive biopsy result after TTMB with previous negative TRUS-Bx. CONCLUSIONS: TTMB is efficient for patients on AS in the detection of upgraded cancer located in anterior or apex or those with previous negative TRUS-Bx in the detection of anterior or apex cancer. In PI-RADSTM score 1-2, a substantial proportion of patients after experienced upgrade in GS on AS patients or cancer detection on previous negative TRUS-Bx. Moreover, we identified prostate volume is the independent predictor for a positive biopsy result after TTMB with previous negative TRUS-Bx.

Changeable Conditional Survival Rates and Associated Prognosticators in Patients with Metastatic Renal Cell Carcinoma Receiving First Line Targeted Therapy.

PURPOSE: In this study we evaluated conditional survival probabilities in patients with metastatic renal cell carcinoma who underwent first line tyrosine kinase inhibitor therapy. We also identified predictors of conditional survival with time. MATERIALS AND METHODS: We retrospectively reviewed clinical data on 1,659 individuals with metastatic renal cell carcinoma in the Korean Renal Cancer Study Group database, of whom the records of 1,131 were finally analyzed. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities using the formula, conditional survival (α│ß) = S(α + ß)/S(ß), indicating the likelihood of additional α years survivorship in person who has already survived for ß years after initial therapy. S(χ) represents the actual survival rate. Multivariate Cox regression model was used to identify predictors of conditional survival with time. RESULTS: Six, 12, 18, 24 and 36-month conditional overall survival gradually increased in patients at all additional survival times after initial treatment compared to patient baseline survival estimations. While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment. Furthermore, predictors of conditional overall survival changed with time. Only previous metastasectomy remained a key prognosticator of conditional overall survival until 36 months of survival following initial tyrosine kinase inhibitor treatment. CONCLUSIONS: Conditional survival improved with time after initial tyrosine kinase inhibitor treatment in patients with metastatic renal cell carcinoma. Our study offers valuable information for practical survival estimations and relevant prognosticators in patients with metastatic renal cell carcinoma who receive first line tyrosine kinase inhibitor.

RFA versus robotic partial nephrectomy for T1a renal cell carcinoma: a propensity score-matched comparison of mid-term outcome.

OBJECTIVE: To compare oncological and functional mid-term outcomes following robotic partial nephrectomy (RPN) and radiofrequency ablation (RFA) for treating T1a renal cell carcinoma (RCC) using propensity score-matching. METHODS: Between December 2008-April 2016, 63 patients from each treatment group were propensity score-matched for age, sex, American Society of Anesthesiologists score, tumour size, tumour laterality, tumour histology, R.E.N.A.L. nephrometry score and preoperative estimated glomerular filtration rate (eGFR). Post-treatment follow-up periods for RPN and RFA ranged from 1-90 months (median, 24.6) and 1-65 months (21), respectively. Tumour location, percentage of eGFR preservation and 2-year recurrence-free survival rate were compared between groups. RESULTS: Exophytic and endophytic RCC occurred in 73.0 % (46/63) and 27.0 % (17/63) of the RPN group, and 52.4 % (33/63) and 47.6 % (30/63) of the RFA group, respectively (p=0.017). There was 91.7 % preservation of eGFR in the RPN group and 86.8 % in the RFA group (p=0.088). Two-year recurrence-free survival rate was 100 % in the RPN and 95.2 % in the RFA group (p=0.029). CONCLUSIONS: RPN provides a higher recurrence-free survival rate than RFA. However, RFA is a better treatment option for an endophytic or recurrent RCC that is difficult to treat with RPN. KEY POINTS: • RPN provides a higher recurrence-free survival rate than RFA. • Unlike RPN, repeat RFA is easy to perform for recurrent RCC. • Endophytic RCC could be better treated with RFA.

Efficacy of First-Line Targeted Therapy in Real-World Korean Patients with Metastatic Renal Cell Carcinoma: Focus on Sunitinib and Pazopanib.

BACKGROUND: To evaluate survival outcomes and prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who received sunitinib (SU) and pazopanib (PZ) as first-line therapy in real-world Korean clinical practice. METHODS: Data of 554 patients with mRCC who received SU or PZ at eight institutions between 2012 and 2016 were retrospectively reviewed. Based on the targeted therapy, the patients were divided into SU (n = 293) or PZ (n = 261) groups, and the clinicopathological variables and survival rates of the two groups were compared. A multivariable Cox proportional hazard model was used to determine the prognostic factors for OS. RESULTS: The median follow-up was 16.4 months (interquartile range, 8.3-31.3). Patients in the PZ group were older, and no significant difference was observed in the performance status (PS) between the two groups. In the SU group, the dose reduction rate was higher and the incidence of grade 3 toxicity was more frequent. The objective response rates were comparable between the two groups (SU, 32.1% vs. PZ, 36.4%). OS did not differ significantly between the two groups (SU, 36.5 months vs. PZ, 40.2 months; log-rank, P = 0.955). Body mass index, Eastern Cooperative Oncology Group PS > 2, synchronous metastasis, poor Heng risk criteria, and liver and bone metastases were associated with a shorter OS. CONCLUSION: Our real-world data of Korean patients with mRCC suggested that SU and PZ had similar efficacies as first-line therapy for mRCC. However, PZ was better tolerated than SU in Korean patients.

Prognostic impact of the pretreatment aspartate transaminase/alanine transaminase ratio in patients treated with first-line systemic tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma.

OBJECTIVES: To examine the prognostic role of the pretreatment aspartate transaminase/alanine transaminase or De Ritis ratio in patients with metastatic renal cell carcinoma receiving first-line systemic tyrosine kinase inhibitor therapy. METHODS: We retrospectively searched the medical records of 579 patients with metastatic renal cell carcinoma who visited Samsung Medical Center, Seoul, Korea, from January 2001 through August 2016. After excluding 210 patients, we analyzed 360 patients who received first-line tyrosine kinase inhibitor therapy. Cancer-specific survival and overall survival were defined as the primary and secondary end-points, respectively. A multivariate Cox proportional hazards regression model was used to identify independent prognosticators of survival outcomes. RESULTS: The overall population was divided into two groups according to the pretreatment De Ritis ratio as an optimal cut-off value of 1.2, which was determined by a time-dependent receiver operating characteristic curve analysis. Patients with a higher pretreatment De Ritis ratio (≥1.2) had worse cancer-specific survival and overall survival outcomes, compared with those with a lower De Ritis ratio (<1.2). Notably, a higher De Ritis ratio (≥1.2) was found to be an independent predictor of both cancer-specific survival (hazard ratio 1.61, 95% confidence interval 1.13-2.30) and overall survival outcomes (hazard ratio 1.69, 95% confidence interval 1.19-2.39), along with male sex, multiple metastasis (≥2), non-clear cell histology, advanced pT stage (≥3), previous metastasectomy and the Memorial Sloan Kettering Cancer Center risk classification. CONCLUSION: Our findings show that the pretreatment De Ritis ratio can provide valuable information about the survival outcomes of metastatic renal cell carcinoma patients receiving first-line tyrosine kinase inhibitor therapy.