Survival improvement over time in renal cell carcinoma treated with nephrectomy: A longitudinal propensity score-matched study.

OBJECTIVE: Surgical treatment for renal cell carcinoma (RCC) has drastically evolved for the past 30 years. However, survival outcomes of RCC according to times have not been fully elucidated, especially in the real-world setting. This study aimed to assess the survival improvement over time in RCC treated with nephrectomy by analyzing a longitudinal cohort using propensity score matching (PSM). METHODS: We retrospectively reviewed 960 patients with RCC who underwent radical or partial nephrectomy between 1981 and 2018. Patients were divided into two groups according to the time of surgery (1981-1999 vs. 2000-2018). Using PSM, overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were compared between the two groups. RESULTS: Overall, 255 and 705 patients underwent surgery in the earlier (1981-1999) and recent (2000-2018) eras, and PSM derived a matched cohort of 466 patients (233 patients per each group). All patients in the earlier era cohort received open surgeries, whereas about a half (47.4%) of patients in the recent era cohort received minimally-invasive (laparoscopic/robotic) surgeries. After PSM, 137 (29.4%) patients developed recurrence, 105 (22.5%) died of RCC, and 113 (24.2%) died from other causes, with a median follow-up period of 90 months. The recent era cohort had significantly longer OS, CSS, and RFS than the earlier era cohort. CONCLUSIONS: Patients with RCC treated in the recent era (2000-2018) showed significantly longer survival than those treated in the earlier era (1981-1999). The improved survival might be attributable to the prevalence of minimally-invasive (laparoscopic/robotic) surgeries.

Retzius-Sparing Robot-Assisted Radical Prostatectomy Using the Hinotori Surgical Robot System Platform: Report of the First Series of Experiences.

BACKGROUND: The aim of this study is to describe the first series of six patients undergoing Retzius-sparing robot-assisted radical prostatectomy (rs-RARP) using the hinotori surgical robot system (hinotori SRS) and to compare the treatment outcomes with those achieved with the da Vinci surgical platform. METHODS: This study included 20 cases involving the rs-RARP procedure (hinotori: N = 6; da Vinci: N = 14) that were performed between May 2021 and April 2024 in a single institution. RESULTS: No significant differences were observed between the hinotori and da Vinci groups regarding the preoperative findings. In the hinotori group, there were four cases of pT2 that showed negative surgical margins in all the cases. However, positive surgical margins were observed in two of the cases with pT3. The surgical outcomes were also similar between the two groups except for console time, which tended to be shorter in the da Vinci group (p = 0.058). There were no major complications in the initial six cases with the hinotori SRS. Immediate urinary continence was observed in 50% of the cases with the hinotori group compared with 64% for the da Vinci group. CONCLUSION: This is the first study to report cases of rs-RARP performed on a hinotori SRS. It seems that the hinotori SRS shows similar treatment outcomes compared with the cases treated via the da Vinci platform.

Development of risk-score model in patients with negative surgical margin after robot-assisted radical prostatectomy.

A total of 739 patients underwent RARP as initial treatment for PCa from November 2011 to October 2018. Data on BCR status, clinical and pathological parameters were collected from the clinical records. After excluding cases with neoadjuvant and/or adjuvant therapies, presence of lymph node or distant metastasis, and positive SM, a total of 537 cases were eligible for the final analysis. The median follow-up of experimental cohort was 28.0 (interquartile: 18.0-43.0) months. We identified the presence of International Society of Urological Pathology grade group (ISUP-GG) ≥ 4 (Hazard ratio (HR) 3.20, 95% Confidence Interval (95% CI) 1.70-6.03, P < 0.001), lymphovascular invasion (HR 2.03, 95% CI 1.00-4.12, P = 0.049), perineural invasion (HR 10.7, 95% CI 1.45-79.9, P = 0.020), and maximum tumor diameter (MTD) > 20 mm (HR 1.9, 95% CI 1.01-3.70, P = 0.047) as significant factors of BCR in the multivariate analysis. We further developed a risk model according to these factors. Based on this model, 1-year, 3-year, and 5-year BCR-free survival were 100%, 98.9%, 98.9% in the low-risk group; 99.1%, 94.1%, 86.5% in the intermediate-risk group; 93.9%, 84.6%, 58.1% in the high-risk group. Internal validation using the bootstrap method showed a c-index of 0.742 and an optimism-corrected c-index level of 0.731. External validation was also carried out using an integrated database derived from 3 other independent institutions including a total of 387 patients for the final analysis. External validation showed a c-index of 0.655. In conclusion, we identified risk factors of biochemical failure in patients showing negative surgical margin after RARP and further developed a risk model using these risk factors.

Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study.

OBJECTIVE: Enfortumab vedotin (EV) was approved for advanced urothelial carcinoma (UC) in 2021 after the EV-301 trial showed its superiority to non-platinum-based chemotherapy as later-line treatment after platinum-based chemotherapy and immune checkpoint inhibitors including pembrolizumab. However, no study has compared EV with rechallenging platinum-based chemotherapy (i.e., "platinum rechallenge") in that setting. METHODS: In total, 283 patients received pembrolizumab for advanced UC after platinum-based chemotherapy between 2018 and 2023. Of them, 41 and 25 patients received EV and platinum rechallenge, respectively, as later-line treatment after pembrolizumab. After excluding two patients with EV without imaging evaluation, we compared oncological outcomes, including progression-free survival (PFS) and overall survival (OS), between the EV (n = 39) and platinum rechallenge groups (n = 25) using propensity score matching (PSM). RESULTS: Analyses on crude data (n = 64) showed no significant differences between the two groups regarding patients' baseline characteristics. PFS (5 months) and OS (11 months) in the EV group were comparable to those (8 and 12 months, respectively) in the platinum rechallenge group. After PSM (n = 36), the baseline characteristics between the two groups became more balanced, and PFS (not reached) and OS (not reached) in the EV group were comparable to those (8 and 11 months, respectively) in the platinum rechallenge group. CONCLUSIONS: EV and platinum rechallenge showed equivalent oncological outcomes, even after PSM, and both treatments should therefore be effective treatment options for post-platinum, post-pembrolizumab advanced UC.

Validation of a drug-based score in advanced urothelial carcinoma treated with pembrolizumab.

Aim: To validate a 'drug score' that stratifies patients receiving immunotherapy based on concomitant medications (antibiotics/proton pump inhibitors/corticosteroids) in urothelial carcinoma (UC). Materials & methods: We assessed oncological outcomes according to the drug score in 242 patients with advanced UC treated with pembrolizumab. Results: The drug score classified patients into three risk groups with significantly different survivals. Heterogeneous treatment effect analyses showed that the primary cancer site (bladder UC [BUC] or upper-tract UC [UTUC]) significantly affected the prognostic capability of the drug score; it significantly correlated with survivals in BUC, while there were no such correlations in UTUC. Conclusion: A drug score was examined in advanced UC treated with pembrolizumab and was validated in BUC but not in UTUC.

Drug treatment for cancer may be weakened by other drugs. We checked whether some kinds of drugs really weakened the effect of drug treatment for cancer. We found that it was true for some kinds of cancer but not for other kinds.

Improved survival in real-world patients with advanced urothelial carcinoma: A multicenter propensity score-matched cohort study comparing a period before the introduction of pembrolizumab (2003-2011) and a more recent period (2016-2020).

OBJECTIVES: Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab. METHODS: This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era. RESULTS: After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months). CONCLUSIONS: Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab.

Clinical characteristics of patients with inguinal hernia mesh migration into the bladder.

Introduction: We report two cases of mesh migration into the bladder after inguinal hernia surgery. Case presentation: In the first case, a 48-year-old woman who underwent right internal inguinal hernia repair, 18 months prior, presented with pollakiuria and microscopic hematuria that was resistant to antibiotics. A submucosal tumor was detected at the bladder dome by cystoscopy, and transurethral resection was performed. Intraoperatively, a migrated mesh was observed in the submucosal lesion. In the second case, a 55-year-old man who underwent a right external inguinal hernia repair, approximately 14 years prior, presented with persistent microscopic hematuria and pyuria. Cystoscopy revealed mesh migration to the upper right bladder wall. Both patients underwent partial cystectomy with mesh removal, and their complaints were resolved after surgery. Conclusion: Mesh migration should be suspected in patients with a history of inguinal hernia repair, accompanied by persistent lower urinary tract symptoms or abnormal urinalysis findings.

Impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis.

BACKGROUND: Several studies have reported the incidence of immune-related adverse events (irAEs) as a predictor of the efficacy of anti-programmed cell death protein 1 antibodies in patients with cancer. However, immortal time bias has not always been fully addressed in these studies. In this retrospective multicenter study, we assessed the association between the incidence of irAEs and the efficacy of pembrolizumab in urothelial carcinoma (UC) using time-dependent analysis, an established statistical method to minimize immortal time bias. METHODS: The study included 176 patients with advanced UC who underwent pembrolizumab treatment at seven affiliated institutions between January 2018 and July 2020. Patients with irAEs were compared with those without irAEs in terms of overall survival (OS) and cancer-specific survival (CSS). Immortal time bias was eliminated by using time-dependent analysis. RESULTS: Of the 176 patients, irAEs occurred in 77 patients (43.8%), with a median of 60 days. The irAEs (+) cohort showed significantly favorable OS and CSS compared with the irAEs (-) cohort (p=0.018 and p=0.005, respectively), especially in the cohort with grade 1-2 irAEs (OS and CSS; p=0.003 and p=0.002, respectively). Multivariate analyses identified any irAEs and grade 1-2 irAEs as independent favorable prognostic factors for OS and CSS. CONCLUSION: Even after minimizing immortal time bias by time-dependent analysis, the incidence of irAEs, especially grade 1-2 irAEs, could be a significant predictor of favorable prognoses in patients with UC who have undergone pembrolizumab treatment.

Prognostic significance of the albumin-to-globulin ratio for advanced urothelial carcinoma treated with pembrolizumab: a multicenter retrospective study.

Although the albumin-to-globulin ratio (AGR) is a promising biomarker, no study has investigated its prognostic significance for advanced urothelial carcinoma (UC). This study conformed to the REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria. We retrospectively reviewed 176 patients with advanced UC treated with pembrolizumab between 2018 and 2020. We evaluated the associations between pretreatment clinicopathological variables, including the AGR and performance status (PS), with progression-free survival, cancer-specific survival, and overall survival. The Cox proportional hazards model was used for univariate and multivariable analyses. The AGR was dichotomized as < 0.95 and ≥ 0.95 based on receiver operating characteristic curve analysis. After excluding 26 cases with missing data from the total of 176 cases, 109 (73%) patients experienced disease progression, 75 (50%) died from UC, and 6 (4%) died of other causes (median survival = 12 months). Multivariate analyses identified PS ≥ 2 and pretreatment AGR < 0.95 as independent poor prognostic factors for all endpoints. Furthermore, a prognostic risk model incorporating these two variables achieved a relatively high concordance index for all endpoints. This is the first report to evaluate the significance of AGR in advanced UC. Pretreatment AGR < 0.95 may serve as a prognostic marker for advanced UC treated with pembrolizumab.

Clinical significance and risk factors of International Society of Urological Pathology (ISUP) grade upgrading in prostate cancer patients undergoing robot-assisted radical prostatectomy.

BACKGROUND: The objective of this study is to investigate the clinical significance and risk factors of upgrading in the International Society of Urological Pathology (ISUP) Grade Group System in men undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer. METHODS: A total of 583 patients diagnosed with prostate cancer by systematic biopsy were treated with RARP without neoadjuvant therapy from November 2011 to December 2018. Clinicopathological data were obtained from our clinical records. ISUP grade upgrading (IGU) was defined as 'ISUP grade in prostatectomy specimen determined to be higher than that in the biopsy specimen'. Clinicopathological factors, including age, PSA, prostate volume at biopsy (PV), PSA density, clinical stage, body mass index (BMI), interval from biopsy to prostatectomy, maximum percentage of cancer involvement per core (%CI), total number of biopsy cores, percentage of cancer positive biopsy cores (%PC), and sampling density were analyzed to detect potential risk factors of IGU. Biochemical recurrence (BCR) rates were calculated to analyze the effect of IGU on cancer prognosis. RESULTS: In univariate analysis, BMI was a positive predictor of IGU, while %CI, %PC, and sampling density were negative predictors of IGU. BMI and %PC were statistically significant predictors of IGU in multivariate analysis. For cases diagnosed as ISUP grade group 2 or higher at biopsy, there was a significant difference in BCR rates between cases with and without IGU. CONCLUSIONS: The results from our cohort showed that elements of both high-grade cancer risk (such as BMI) and sampling efficiency (such as %PC) contribute to IGU. Excluding cases diagnosed as ISUP grade group 1 at biopsy, BCR-free rates were significantly worse in cases with IGU, highlighting the need for more accurate pathological diagnosis at biopsy.

Clinical significance and risk factors of urethrovesical anastomotic urinary leakage following robot-assisted radical prostatectomy: a multi-institutional study.

BACKGROUND: There has been a limited number of reports on the significance and risk factors of urethrovesical anastomotic urinary leakage (AUL) following robot-assisted radical prostatectomy (RARP). We aimed to analyze the clinical significance of AUL and evaluated its risk factors. METHODS: We conducted a multi-institutional study to review patients with prostate cancer undergoing RARP in three centers (The University of Tokyo Hospital, Mitsui Memorial Hospital, and Chiba Tokushukai Hospital). "Positive AUL" was defined as urinary extravasation at the anastomosis detected by post-operative cystogram and was further categorized into minor or major AUL. Univariate and multivariate analyses were performed to identify predictors of AUL. Postoperative continence rates and time to achieve continence were also analyzed. RESULTS: A total of 942 patients underwent RARP for prostate cancer in 3 centers. Of these patients, a cystogram after the RARP procedure was not performed in 26 patients leaving 916 patients for the final analysis. AUL was observed in 56 patients (6.1%); 34 patients (3.7%) with minor AUL and 22 patients (2.4%) with major AUL. Patients with major AUL exhibited a significantly longer time to achieve continence than those without major AUL. Multivariate analysis demonstrated that longer console time (≥ 184 min) was significantly associated with overall AUL, and higher body mass index (≥ 25 g/kg2) was a significant predictor of both major and overall AUL. CONCLUSIONS: The presence of major AUL was associated with the achievement of urinary continence, suggesting clinical relevance of its diagnosis by postoperative cystogram. A selective cystogram has been proposed for high-risk cases. Furthermore, identification of the risk factors of AUL will lead to optimal application.

Comparison of perioperative outcomes in elderly (age ≧ 75 years) vs. younger men undergoing robot-assisted radical prostatectomy.

OBJECTIVES: To investigate perioperative, oncologic, and functional outcomes of robot-assisted radical prostatectomy (RARP) in men of age ≥ 75 years in comparison with younger men. METHODS: From November 2011 to December 2018, six hundred and thirty patients with prostate cancer underwent robot-assisted radical prostatectomy (RARP). A total of 614 patients were analyzed after excluding 16 patients who were treated with hormone therapy prior to RARP. Patients were divided into 2 groups based on their age (age ≥ 75 years: N = 46 patients and age < 75 years: N = 568 patients). Perioperative parameters regarding oncologic/functional outcomes and complication status were compared between the 2 groups. Clavien-Dindo classification was used to classify perioperative complications. Clinical and pathological status including stage, positive margin, continence, and potency status after RARP were analyzed. RESULTS: Five-hundred sixty-eight and forty-six men were of age <75 and ≥ 75 years, respectively. There were no significant differences between the 2 groups in terms of oncologic outcomes (positive resection margin rate and PSA failure). The duration of hospitalization was longer in older patients but was not statistically significant (P = 0.051). A total number of Clavien ≥3 complications that occurred within a month after RARP were 15 (2.6%) and 2 (4.3%) in younger men (age < 75 years) and older men (age ≥ 75 years), respectively (P = 0.359). CONCLUSION: The present study showed that the oncologic and surgical outcomes in the elderly group were similar to those in the younger population. However, the duration of hospitalization seemed to be longer in older patients (age ≥ 75 years), despite similar complication rates.

Prospective evaluation of visual function in patients with ocular diseases after robot-assisted laparoscopic prostatectomy.

OBJECTIVES: To investigate intraocular pressure and visual function in patients with ocular diseases undergoing robot-assisted laparoscopic prostatectomy. METHODS: We carried out a prospective clinical study of patients undergoing robot-assisted laparoscopic prostatectomy for localized prostate cancer at The University of Tokyo Hospital from December 2015 to March 2017. An ophthalmologist measured intraocular pressure, and carried out visual field testing at 0-2 months before and 7 days after robot-assisted laparoscopic prostatectomy. During the surgery, an anesthesiologist measured intraocular pressure at specified time points. RESULTS: A total of 110 patients were enrolled and 98 eligible patients were analyzed; 37 were diagnosed with ocular diseases before robotic-assisted laparoscopic prostatectomy (17 with glaucoma, 20 with other ocular diseases). Intraocular pressure significantly increased during robot-assisted laparoscopic prostatectomy. Transient postoperative visual field defect was detected in 24 eyes of 17 patients, including six patients with ocular diseases at 7 days after surgery. At 3 months after surgery, one of 34 glaucomatous eyes and one of 40 eyes with non-glaucomatous ocular diseases continued to show visual field defect, although visual field defect in the remaining patients recovered to preoperative conditions within 3 months. CONCLUSIONS: Our findings suggest that robot-assisted laparoscopic prostatectomy can be safely carried out in patients with ocular diseases, even those with glaucoma, after precautionary consultation with an ophthalmologist.

Drug review: Pazopanib.

Pazopanib (Votrient®) is an oral small-molecule multi-kinase inhibitor that primarily inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet endothelial growth factor receptor-α, and -ß, and the stem-cell factor receptor c-kit. In preliminary experiments using angiogenesis models with mice and rabbits, pazopanib inhibited angiogenesis caused by combined vascular endothelial growth factor and basic fibroblast growth factor. Although pazopanib was developed as a therapeutic agent against various tumors, it is currently approved in many countries for advanced soft-tissue sarcoma and renal cell carcinoma. The importance of pazopanib has been acknowledged, with positive results demonstrated in large-scale clinical trials involving patients with soft-tissue sarcoma and renal cell carcinoma. However, adverse events such as liver dysfunction and hypertension are common, often necessitating treatment discontinuation. These adverse events are generally manageable, and from the perspective of health-related quality of life and cost-effectiveness, pazopanib provides an improvement in quality-adjusted life years and decreases the treatment cost compared with other alternatives. In this review, we present the results of clinical trials and discuss the pharmacological action of pazopanib, with the aim of evaluating its current state by examining various associated issues.

Incidence and risk factors of inguinal hernia after robot-assisted radical prostatectomy.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) has now become a gold standard approach in radical prostatectomy. The aim of this study was to investigate incidence and risk factors of inguinal hernia (IH) after RARP. METHODS: This study included 307 consecutive men who underwent RARP for the treatment of prostate cancer from January 2011 to August 2015. The incidence of IH after RARP was investigated. Clinical and pathological factors were also investigated to assess relationship with development of postoperative IH. RESULTS: Median follow-ups were 380 days, and median age of patients was 67 years. Incidence of IH was 11.3, 14.0, and 15.4% at 1, 2, and 3 years after RARP, respectively. Postoperative IH occurrence was significantly associated with low surgeon experience and postoperative incontinence at 3 or 6 months after surgery (P = 0.019, P = 0.002, and P = 0.016, respectively). CONCLUSIONS: Most of the IH occurred within the first 2 years with a rate of 14%. Incidence of IH after RARP was significantly associated with surgical experience and incontinence outcomes.

A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor.

Tripartite motif 44 (TRIM44) is one of the TRIM family proteins that are involved in ubiquitination and degradation of target proteins by modulating E3 ubiquitin ligases. TRIM44 overexpression has been observed in various cancers. However, its association with testicular germ cell tumor (TGCT) is unknown. We aimed to investigate the clinical significance of TRIM44 and its function in TGCT. High expression of TRIM44 was significantly associated with α feto-protein levels, clinical stage, nonseminomatous germ cell tumor (NSGCT), and cancer-specific survival (P = 0.0009, P = 0.0035, P = 0.0004, and P = 0.0140, respectively). Multivariate analysis showed that positive TRIM44 IR was an independent predictor of cancer-specific mortality (P = 0.046). Gain-of-function study revealed that overexpression of TRIM44 promoted cell proliferation and migration of NTERA2 and NEC8 cells. Knockdown of TRIM44 using siRNA promoted apoptosis and repressed cell proliferation and migration in these cells. Microarray analysis of NTERA2 cells revealed that tumor suppressor genes such as CADM1, CDK19, and PRKACB were upregulated in TRIM44-knockdown cells compared to control cells. In contrast, oncogenic genes including C3AR1, ST3GAL5, and NT5E were downregulated in those cells. These results suggest that high expression of TRIM44 is associated with poor prognosis and that TRIM44 plays significant role in cell proliferation, migration, and anti-apoptosis in TGCT.

Optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy: is ultra-early salvage radiotherapy beneficial?

BACKGROUND: The optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy is controversial. In particular, the prognostic significance of salvage radiotherapy delivered before a current definition of biochemical recurrence, i.e. ultra-early salvage radiotherapy, is unclear. METHODS: We reviewed 76 patients with pT2-3N0M0 prostate cancer who underwent salvage radiotherapy for post-prostatectomy biochemical recurrence at the following three timings: ultra-early salvage radiotherapy (n = 20) delivered before meeting a current definition of biochemical recurrence (two consecutive prostate-specific antigen [PSA] values ≥0.2 ng/mL); early salvage radiotherapy (n = 40) delivered after meeting the definition but before PSA reached 0.5 ng/mL; and delayed salvage radiotherapy (n = 16) delivered after PSA reached 0.5 ng/mL. The primary endpoint was failure of salvage radiotherapy, defined as a PSA value ≥0.2 ng/mL. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. RESULTS: During the follow-up period (median: 70 months), four of 20 (20 %), nine of 40 (23 %) and seven of 16 (44 %) patients failed biochemically in the ultra-early, early and delayed salvage radiotherapy groups, respectively. On univariate analyses, the outcome of delayed salvage radiotherapy was worse than the others, while there was no significant difference between ultra-early and early groups. Multivariate analysis demonstrated the presence of Gleason pattern 5, perineural invasion and delayed salvage radiotherapy as independent predictors of poorer survival. CONCLUSIONS: No survival benefit of ultra-early salvage radiotherapy was demonstrated, whereas delayed salvage radiotherapy was associated with worse outcome as reported in previous studies. Our results may support the current recommendations that salvage radiotherapy should be undertaken after two consecutive PSA values ≥0.2 ng/mL and before reaching 0.5 ng/mL.

Impact of Gleason pattern 5 including tertiary pattern 5 on outcomes of salvage treatment for biochemical recurrence in pT2-3N0M0 prostate cancer.

BACKGROUND: Gleason pattern 5 (GP5), including tertiary GP5, at radical prostatectomy has reportedly been associated with poorer clinical outcome. However, it is undetermined how tertiary GP5 is handled in the new Gleason grade grouping starting in 2016, and its prognostic value in patients undergoing salvage treatment for postoperative biochemical recurrence (BCR) remains unclear. METHODS: We retrospectively reviewed 116 patients with pT2-3N0M0 prostate cancer (PC) who received salvage treatment for BCR after radical prostatectomy between 2003 and 2014. The primary endpoint was failure of salvage treatment, defined as a single prostate-specific antigen (PSA) value ≥0.2 ng/ml after PSA nadir following salvage treatment. Associations of various clinicopathological factors, including GP5, with failure-free survival were assessed. Cox proportional hazards model was used for multivariate analysis. RESULTS: Patients received salvage treatment with either radiotherapy (n = 48), androgen-deprivation therapy (n = 61), or both (n = 7) for BCR. Twenty-three patients (19.8 %) experienced failure of salvage treatment, with a median follow-up period of 79 months. Univariate analysis associated GP5, Gleason score-based parameters, lymphovascular invasion, and PSA doubling time <6 months with poorer failure-free survival. Receiver operating characteristic curve analyses identified the area under the curve for GP5 (0.654) as the largest among those parameters (P = 0.0060). Multivariate analysis demonstrated that GP5 was the only independent predictor of poor outcome. CONCLUSIONS: The presence of GP5 is an independent predictor of poor prognosis in patients with pT2-3N0M0 PC undergoing salvage treatment for BCR after radical prostatectomy. GP5 may thus be a more useful marker than conventional Gleason score in this setting.

Symptoms at diagnosis as independent prognostic factors in retroperitoneal liposarcoma.

The prognostic factors of retroperitoneal liposarcoma have yet to be clearly determined due to its rarity, whereas the prognostic value of symptoms at diagnosis has never been evaluated to date. In this context, we reviewed 24 consecutive patients with primary retroperitoneal liposarcoma who underwent surgical resection with curative intent at our institution. The Kaplan-Meier analysis and the log-rank test were used to estimate progression-free survival (PFS; primary endpoint) and sarcoma-specific survival (SSS; secondary endpoint). The effect of various clinicopathological factors, including symptoms at diagnosis, on these two endpoints was assessed with a Cox proportional hazards model. During the study period, 11 patients (45.8%) developed recurrence after the initial surgery and 8 (33.3%) succumbed to retroperitoneal liposarcoma, with a median follow-up of 64 months. A total of 16 patients (66.7%) had symptoms at diagnosis, while the remaining 8 (33.3%) were diagnosed incidentally. The symptoms were palpability of the tumor (n=8); abdominal pain/fullness (n=3); flank pain/fullness (n=2); lower extremity pain (n=1); testicular pain due to varicocele (n=1); and discomfort on urination (n=1). Patients with symptoms at diagnosis were significantly more likely to develop recurrence (log-rank test, P=0.0196) and were also more likely to succumb to sarcoma (P=0.0778) compared with asymptomatic patients. On the multivariate analysis, symptoms at diagnosis and dedifferentiated components were independent predictors of poor PFS, while positive surgical margins were predictors of poor SSS. Given that symptoms at diagnosis are easily accessible for physicians, they may prove to be useful additional prognostic factors for primary retroperitoneal liposarcoma.