Diagnostic performance of photodynamic diagnosis with oral 5-aminolevulinic acid for upper tract- and bladder urothelial carcinoma: a single-centre, retrospective analysis.

PURPOSE: To compare the diagnostic performance of photodynamic diagnosis (PDD) enhanced with oral 5-aminolaevulinic acid between the suspected upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) cases. METHODS: This retrospective study included 18 patients with suspected UTUC who underwent ureteroscopy (URS) with oral 5-ALA in the PDD-URS cohort between June 2018 and January 2019; and 110 patients with suspected BUC who underwent transurethral resection of bladder tumour (TURBT) in the PDD-TURBT cohort between January 2019 and March 2023. Sixty-three and 708 biopsy samples were collected during diagnostic URS and TURBT, respectively. The diagnostic accuracy of white light (WL) and PDD in the two cohorts was evaluated, and false PDD-positive samples were pathologically re-evaluated. RESULTS: The area under the receiver operating characteristic curve (AUC) of PDD was significantly superior to that of WL in both cohorts. The per biopsy sensitivity, specificity, and positive and negative predictive values of PDD in patients in the PDD-URS and PDD-TURBT cohorts were 91.2 vs. 71.4, 75.9 vs. 75.3, 81.6 vs. 66.3, and 88.0 vs. 79.4%, respectively. The PDD-URS cohort exhibited a higher AUC than did the PDD-TURBT cohort (0.84 vs. 0.73). Seven of four false PDD-positive samples (57.1%) in the PDD-URS cohort showed potential precancerous findings compared with eight of 101 (7.9%) in the PDD-TURBT cohort. CONCLUSION: The diagnostic performance of PDD in the PDD-URS cohort was at least equivalent to that in the PDD-TURBT cohort.

Identification of the factor affecting learning curves of laparoscopic gastrectomy through the experience at a Japanese high-volume center over the last decade.

Background: Though laparoscopic gastrectomy (LG) has become the gold standard for gastric cancer treatment according to the Japanese treatment guidelines, its learning curve remains steep. Decreasing numbers of surgeons and transitions in the work environment have changed LG training recently. We analyzed LG training over the last decade to identify factors affecting the learning curve. Study Design: Laparoscopic distal and pylorus-preserving gastrectomies conducted between 2010 and 2020 were included. We assessed learning curves based on the standard operation time (SOT) defined by analysis of covariance. Then we divided the trainees into two groups based on the length of the learning curve and examined the factors affecting the learning curve with linear regression analysis. Results: Among 2335 LGs, 960 cases treated by 27 trainees and 1301 cases treated by six attending surgeons were analyzed. The operation time was prolonged (p = 0.009) and postoperative morbidity rates were lower (p = 0.0003) for cases treated by trainees. Trainees experienced 38 (range, 9-81) cases as scopists and nine (range, 0-41) cases as first assistants to the first operator. The learning curve was approximately 30 cases. The SOT was calculated based on gender, body mass index, tumor location, reconstruction, and lymph node dissection. Trainees who had shorter learning curves had more experience (51-100 cases) with any laparoscopic surgery before LG training than the others (11-50 cases, p = 0.017). Conclusion: Sufficient experience with laparoscopic surgery before starting LG training might contribute to the efficiency of LG training and shorten the learning curve.

Clinical factors predicting the outcome of salvage radiotherapy for patients with biochemical recurrence after radical prostatectomy.

BACKGROUND: It remains unclear which patients with biochemical recurrence after prostatectomy are most suitable for salvage radiotherapy. We evaluated the parameters related to outcomes. METHODS: We retrospectively evaluated patients who underwent salvage therapy for biochemical recurrence after prostatectomy between 2005 and 2019. This study aimed to evaluate biochemical recurrence-free survival (bRFS) after salvage radiotherapy and elucidate the parameters associated with bRFS. The bRFS rate was calculated using the Kaplan-Meier method, and the parameters associated with bRFS were evaluated using Cox regression analysis. RESULTS: This study included 67 patients treated with salvage radiotherapy with a median age of 67 years at salvage radiotherapy. The median follow-up period after salvage radiotherapy was 7.3 years. The 5-year bRFS rate following salvage radiotherapy was 47.1%. Univariate analysis showed that PSA doubling time < 6 months, positive surgical margin, and pathological Gleason score ≥ 8 were significantly associated with shorter bRFS (p < 0.001, p = 0.036, p = 0.047, respectively). Multivariable analysis showed that a PSA doubling time < 6 months and positive surgical margins were significantly associated with shorter bRFS (p = 0.001 and p = 0.018, respectively). No serious adverse events were observed. CONCLUSIONS: In our hospital, approximately half of the patients are under long-term control with salvage radiotherapy. A PSA doubling time of < 6 months and positive surgical margins were suggested to be associated with poor outcomes of salvage radiotherapy.

Oncological outcomes of prophylactic urethrectomy at the time of radical cystectomy for bladder cancer: A nationwide multi-institutional study.

OBJECTIVES: To determine the effects of prophylactic urethrectomy (PU) on oncological and perioperative outcomes in patients with bladder cancer (BC) undergoing radical cystectomy (RC). METHODS: This retrospective study analyzed data on 1976 evaluable patients with BC who underwent RC. Patients were drawn from 36 institutions within the Japanese Urological Oncology Group. Oncological outcomes were compared using restricted mean survival times (RMSTs) based on inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves for non-urinary tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Interaction terms within IPTW-adjusted Cox regression models were examined to assess the heterogeneity of treatment effect based on the risk of urethral recurrence (UR). The association between PU, estimated blood loss (EBL), and the incidence of severe postoperative surgical complications (SPSCs) (Clavien-Dindo grade 3 or higher) was analyzed. RESULTS: Of 1976 patients, 1448 (73.3%) received PU. IPTW adjustment was used to balance baseline characteristics between the treatment groups. Within the 107-month window of patient monitoring, PU showed no survival benefits (NUTRFS difference: 0.2 months [95% confidence interval: -6.8 to 7.3]; CSS, 1.2 [-4.9 to 7.3]; OS, 0 [-6.5 to 6.5]). No significant interactions were observed with factors associated with UR, and PU was associated with unfavorable perioperative outcomes (EBL, 1179 mL vs. 983 mL; SPSC, 14.6% vs. 7.0%). CONCLUSIONS: This study showed that (1) PU was not associated with survival in patients with BC undergoing RC, regardless of UR-associated factors, and (2) PU was associated with unfavorable perioperative outcomes.

J-AVENUE: A retrospective, real-world study evaluating patient characteristics and outcomes in patients with advanced urothelial carcinoma treated with avelumab first-line maintenance therapy in Japan.

OBJECTIVES: The JAVELIN Bladder 100 phase 3 trial showed that avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with advanced urothelial carcinoma who were progression-free following first-line platinum-based chemotherapy. We report findings from J-AVENUE (NCT05431777), a real-world study of avelumab first-line maintenance therapy in Japan. METHODS: Medical charts of patients with advanced urothelial carcinoma without disease progression following first-line platinum-based chemotherapy, who received avelumab maintenance between February and November 2021, were reviewed. Patients were followed until June 2022. The primary endpoint was patient characteristics; secondary endpoints included time to treatment failure and progression-free survival. RESULTS: In 79 patients analyzed, median age was 72 years (range, 44-86). Primary tumor site was upper tract in 45.6% and bladder in 54.4%. The most common first-line chemotherapy regimen was cisplatin + gemcitabine (63.3%). Median number of chemotherapy cycles received was four. Best response to chemotherapy was complete response in 10.1%, partial response in 58.2%, and stable disease in 31.6%. Median treatment-free interval before avelumab was 4.9 weeks. With avelumab first-line maintenance therapy, the disease control rate was 58.2%, median time to treatment failure was 4.6 months (95% CI, 3.3-6.4), and median progression-free survival was 6.1 months (95% CI, 3.6-9.7). CONCLUSIONS: Findings from J-AVENUE show the effectiveness of avelumab first-line maintenance in patients with advanced urothelial carcinoma in Japan in clinical practice, with similar progression-free survival to JAVELIN Bladder 100 and previous real-world studies, supporting its use as a standard of care.

Clinical impact of skeletal muscle mass change during the neoadjuvant chemotherapy period in patients with gastric cancer: An ancillary study of JCOG1002.

BACKGROUND: Recent studies have revealed that sarcopenia is associated with postoperative complications and poor prognosis. Although neoadjuvant chemotherapy is a promising treatment for gastric cancer, its toxicity may lead to the loss of skeletal muscle mass. This study investigates the changes in skeletal muscle mass during neoadjuvant chemotherapy and its clinical impact on patients with locally advanced gastric cancer. METHODS: Fifty patients who completed two courses of neoadjuvant chemotherapy followed by surgery were included. Skeletal muscle mass was measured using computed tomography images before and after chemotherapy. The proportion of skeletal muscle mass change (%SMC) during neoadjuvant chemotherapy and its cutoff value was explored using the receiver operating characteristic for the overall survival of patients undergoing R0 resection. Risk factors of skeletal muscle mass loss were also evaluated. RESULTS: Overall, 64% of patients had skeletal muscle mass loss during neoadjuvant chemotherapy (median %SMC -3.4%; range: -18.9% to 10.3%). Multivariable analysis identified older age (≥70 years) as an independent predictor of skeletal muscle mass loss (mean [95% confidence interval]: -4.70% [-8.83 to -0.58], p = 0.026). Among 43 patients undergoing R0 resection, %SMC <-6.9% was an independent poor prognostic factor for overall survival (hazard ratio, 11.53; 95% confidence interval, 2.78-47.80) and relapse-free survival (hazard ratio 4.54, 95% confidence interval 1.50-13.81). CONCLUSIONS: Skeletal muscle mass loss occurs frequently during neoadjuvant chemotherapy for locally advanced gastric cancer and could adversely affect survival outcomes.

Clinical Impact of Polyglycolic Acid Mesh to Reduce Pancreas-Related Complications After Minimally Invasive Surgery for Gastric Cancer: A Propensity Score Matching Analysis.

PURPOSE: Prevention of pancreas-related complications after gastric cancer surgery is critical. Polyglycolic acid (PGA) mesh reduces postoperative pancreatic fistula formation following pancreatic resection. However, the clinical efficacy of PGA mesh in gastric cancer surgery has not been adequately investigated. MATERIALS AND METHODS: This retrospective study compared the short-term outcomes between two groups: patients who underwent minimally invasive R0 gastrectomy for gastric cancer with the use of a PGA mesh (PGA group) and those without the use of a PGA mesh (non-PGA group) at the Cancer Institute Hospital, Tokyo, between January 2019 and May 2023. Propensity score matching (PSM) was performed to adjust for the possible confounding factors. RESULTS: A total of 834 patients were initially included, of whom 614 (307 in each group) remained after PSM. The amylase levels in the drained abdominal fluid on postoperative days 1 and 3 were similar between the PGA and non-PGA groups. The PGA group had a significantly lower incidence of pancreas-related complications of Clavien-Dindo grade ≥2 than that in the non-PGA group (6.8% vs. 2.9%, P=0.025). In subgroup analyses, the odds ratio for pancreas-related complications appeared to be better in the PGA group than in the non-PGA group in patients with American Society of Anesthesiologists Physical Status Classification score of 2 or 3, those operated via a laparoscopic approach, and those undergoing procedures other than proximal gastrectomy. CONCLUSIONS: The use of PGA mesh significantly reduced pancreas-related complications after minimally invasive surgery for gastric cancer and might thus benefit patients at risk of such complications.

Equal short-term outcomes of intracorporeal mechanical gastrogastrostomy in laparoscopic pylorus-preserving gastrectomy for cT1N0 gastric cancer in the middle stomach compared with the extracorporeal hand-sewing method.

BACKGROUND: Intracorporeal mechanical gastrogastrostomy (IMG) techniques have recently been developed and their short-term safety was presented in their initial evaluation. However, whether they are comparable to extracorporeal hand-sewing gastrogastrostomy (EHG) remains unclear. The aim of the study is to establish the safety of IMG in totally laparoscopic pylorus-preserving gastrectomy (TLPPG) compared to EHG in laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG). METHODS: We retrospectively analyzed the short-term outcomes of patients with middle-third early gastric cancer who underwent LAPPG or TLPPG between 2005 and 2022. The primary objective of this study was to evaluate the non-inferiority of IMG to EHG in terms of safety, with the primary endpoint being the risk difference in anastomosis-related complications (ARCs). The sample size required to achieve a statistical power of 80% for the non-inferiority test was 971 with a one-sided alpha level of 5% and non-inferiority of 5%. RESULTS: The analysis included a total of 1,021 patients who underwent LAPPG or TLPPG during the study period. Among them, 488 patients underwent EHG, while 533 underwent IMG. The incidences of ARCs were 11.3% and 11.4% in EHG and IMG, respectively. The observed difference in incidence was 0.0017 (90% confidence interval - 0.0313 to 0.0345), which statistically demonstrated the non-inferiority of IMG to EHG in the incidence of ARCs. Among other complications, the incidence of wound infection in IMG was lower than that in EHG. CONCLUSION: IMG is safe regarding ARCs compared with EHG. These results will encourage surgeons to introduce IMG for patients with early middle gastric cancer.

Peripheral neuropathy and nerve electrophysiological changes with enfortumab vedotin in patients with advanced urothelial carcinoma: a prospective multicenter cohort study.

BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.

Impact of preoperative prealbumin levels on long-term prognosis in patients with gastric cancer after gastrectomy: a retrospective cohort study.

BACKGROUND: The relationship between preoperative prealbumin levels and long-term prognoses in patients with gastric cancer after gastrectomy has not been fully investigated. This study clarified the effect of preoperative prealbumin levels on the long-term prognosis of patients with gastric cancer after gastrectomy. METHODS: This retrospective cohort study included consecutive patients who underwent radical gastrectomy for primary pStage I-III gastric cancer and whose preoperative prealbumin levels were measured between May 2006 and March 2017. Participants were categorized according to their preoperative prealbumin levels into high (≥22 mg/dL), moderate (15-22 mg/dL), and low (<15 mg/dL) groups. The overall survival (OS) in the three groups was compared using the log-rank test, and prognostic factors were identified using Cox proportional hazards regression analysis. RESULTS: The median follow-up duration was 66 months. Of 4732 patients, 3649 (77.2%) were classified as high, 925 (19.6%) as moderate, and 158 (3.3%) as low. Lower prealbumin levels were associated with poorer prognoses (P < 0.001). Multivariate analysis showed that prealbumin levels of 15-22 mg/dL [hazard ratio (HR): 1.576, 95% confidence interval (CI): 1.353-1.835, P < 0.001] and <15 mg/dL (HR: 1.769, 95% CI: 1.376-2.276, P < 0.001) were independent poor prognostic factors for OS. When analyzed according to the cause of death, prealbumin levels were associated with other-cause survival, but not cancer-specific survival. CONCLUSIONS: Preoperative prealbumin levels correlated with OS in patients with gastric cancer after gastrectomy; the lower the prealbumin level, the worse is the prognosis. Prealbumin levels may be associated with other-cause survival.

Prognostic impact of histological discordance between transurethral resection and radical cystectomy.

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.

Association between the antiadhesion membrane and small bowel obstruction after open gastrectomy: A supplemental analysis of the randomized controlled JCOG1001 trial.

Aim: Postoperative small bowel obstruction (SBO) is one of the major complications that is mainly caused by postoperative adhesion. Recently, the antiadhesion membrane has become popular for postoperative SBO prevention. However, its efficacy is yet to be confirmed in the gastric cancer surgery field. Here, we conducted the supplemental analysis of the randomized controlled trial JCOG1001 to investigate the efficacy of the antiadhesion membrane on SBO prevention in patients with open gastrectomy for gastric cancer. Methods: Of the 1204 patients enrolled in JCOG1001, 1200 patients were included. The development of SBO of Grade ≥ IIIa according to the Clavien-Dindo classification was recorded. Univariable and multivariable analyses were performed using the Fine and Gray model to determine the risk factors for SBO. Results: Fifty-one patients developed SBO (median follow-up duration: 5.6 years). Total gastrectomy, combined resection, and blood loss significantly increased the risk for SBO development in the univariable analysis. Large amount of blood loss was independently associated with SBO development in the multivariable analysis (hazard ratio [HR], 3.089; 95% confidence interval [CI], 1.562-6.109, p = 0.0012). Antiadhesion membrane did not reduce the risk for SBO (HR, 1.299; 95% CI 0.683-2.470; p = 0.4246). In the patients belonging to subgroup analyses who received distal and total gastrectomy, the antiadhesion membrane was not associated with the incidence of SBO. Conclusions: Antiadhesion membrane did not decrease SBO occurrence rate after open gastrectomy. Therefore, the use of antiadhesion membrane would not be effective for preventing SBO in gastric cancer surgery.

Long-term Recurrence Rates of Low-risk Non-muscle-invasive Bladder Cancer-How Long Is Cystoscopic Surveillance Necessary?

BACKGROUND: While low-risk non-muscle-invasive bladder cancer (LR-NMIBC) has a low propensity to progress, the risk of recurrence remains high (50% within 4 yr). Guidelines recommend cystoscopic surveillance after resection, but the necessary duration of follow-up is debated. OBJECTIVE: To determine the risk of recurrence beyond 5 yr after diagnosis in patients with LR-NMIBC, and to identify risk factors of recurrence. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter retrospective observational study, patients who received their first transurethral bladder tumor resection before 2016 for LR-NMIBC were included. Low risk was defined as a primary, solitary, low grade, Ta bladder tumor measuring <3 cm. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was determination of the recurrence rates at 1, 2, and 5 yr. The secondary endpoints included overall recurrence-free survival (RFS) and high-risk RFS. A univariate analysis and multivariable logistic regression were performed to assess the risk factors for recurrence over the study period. RESULTS AND LIMITATIONS: The median age of the 577 patients was 70.9 yr, and 126 (21.8%) patients were female. The median follow-up was 69.6 (interquartile range: 58.4) mo, and recurrence was observed in 236 (40.9%) patients. The 1-, 2-, and 5-yr RFS rates were 81.6% (95% confidence interval 78.4-84.9), 72.4% (68.7-76.3), and 59.2% (55-63.8), respectively. Recurrence after 5 yr was observed in 13.1% (28/213). High-risk recurrence, defined as the first recurrence of a high-grade and/or ≥T1 tumor, occurred in 6.2% (36/579) overall and 2.8% (6/213) after 5 yr. The lack of a single postoperative dose of chemotherapy and tumor size >2 cm were prognostic factors of recurrence. CONCLUSIONS: The risk of recurrence in patients with LR-NMIBC decreases progressively after the 1st year and remains low beyond 5 yr. Discontinuation of endoscopic surveillance after 5 yr in patients with LR-NMIBC can be discussed. Treatment with postoperative chemotherapy and tumor size <2 cm may be relevant variables to identify patients who will benefit from cystoscopic follow-up as short as 12 mo. PATIENT SUMMARY: In this study, we observed that 13% of patients who did not have a recurrence during the first 5 yr following the diagnosis of low-risk non-muscle-invasive bladder cancer will recur after this time point. Discontinuation of cystoscopic surveillance can be discussed after 5 yr in these patients.

5-year follow-up results of a JCOG1104 (OPAS-1) phase III non-inferiority trial to compare 4 courses and 8 courses of S-1 adjuvant chemotherapy for pathological stage II gastric cancer.

BACKGROUND: Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is the standard treatment for pathological stage II gastric cancer. The phase III trial (JCOG1104) investigating the non-inferiority of four courses of S-1 to eight courses was terminated due to futility at the first interim analysis. To confirm the primary results, we reported the results after a 5-years follow-up in JCOG1104. METHODS: Patients histologically diagnosed with stage II gastric cancer after radical gastrectomy were randomly assigned to receive S-1 for eight or four courses. In detail, 80 mg/m2/day S-1 was administered for 4 weeks followed by a 2-week rest as a single course. RESULTS: Between February 16, 2012, and March 19, 2017, 590 patients were enrolled and randomly assigned to 8-course (295 patients) and 4-course (295 patients) regimens. After a 5-years follow-up, the relapse-free survival at 3 years was 92.2% for the 8-course arm and 90.1% for the 4-course arm, and that at 5 years was 87.7% for the 8-course arm and 85.6% for the 4-course arm (hazard ratio 1.265, 95% CI 0.846-1.892). The overall survival at 3 years was 94.9% for the 8-course arm, 93.2% for the 4-course arm, and that at 5 years was 89.7% for the 8-course arm, and 88.6% for the 4-course arm (HR 1.121, 95% CI 0.719-1.749). CONCLUSIONS: The survival of the four-course arm was slightly but consistently inferior to that of the eight-course arm. Eight-course S-1 should thus remain the standard adjuvant chemotherapy for pathological stage II gastric cancer.

Long-term impact of sarcopenia in older patients undergoing gastrectomy for gastric cancer: a systematic review and meta-analysis.

Background: Sarcopenia is an inevitable problem in older patients. After gastrectomy, patients often have an inadequate dietary intake and easily fall into sarcopenia. However, the impact of preoperative sarcopenia on long-term outcomes after gastrectomy has not been analyzed. Methods: A systematic review was conducted for all relevant articles identified on PubMed, the Cochrane Library, Web of Science, and ClinicalTrials.gov until April 2023. Adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the fixed or random effects model according to the heterogeneity. The Newcastle-Ottawa Scale was used to quantify study quality. Results: Seven studies involving 1,831 patients aged ≥65 years who underwent gastrectomy for gastric cancer were analyzed. Four hundred twelve patients (22.5%) were diagnosed with sarcopenia. The analysis showed that preoperative sarcopenia was significantly associated with poor overall survival (OS) (HR =1.93; 95% CI:1.60-2.34; P<0.001). Two of the included studies also showed that preoperative sarcopenia was significantly correlated with disease-related survival: one with disease-specific survival (DSS) (HR =4.00; 95% CI: 1.20-13.3, P=0.024) and the other with non-cancer specific survival (HR =3.27; 95% CI: 1.61-6.67; P=0.001). Furthermore, sarcopenic patients experienced more severe complications than non-sarcopenic patients (OR =1.80; 95% CI: 1.10-2.95; P=0.019). Conclusions: This meta-analysis suggested that preoperative sarcopenia is useful as a prognostic factor of impaired OS in older patients after gastrectomy. Preoperative evaluation and intervention for skeletal muscle loss should be considered. Further studies of sarcopenic impact on disease-related survival are required.

Current trends in the promising immune checkpoint inhibition and radiotherapy combination for locally advanced and metastatic urothelial carcinoma.

Locally advanced and metastatic urothelial carcinoma (UC) remains a challenging malignancy, though several novel therapeutic drugs have been developed in recent years. Over the past decade, immune checkpoint inhibitors (ICI) have shifted the paradigm of therapeutic strategies for UC; however, only a limited number of patients respond to ICI. Since radiotherapy (RT) is widely known to induce systemic immune activation, it may boost the efficacy of ICI. Conversely, RT also causes exhaustion of cytotoxic T cells, and the activation and recruitment of immunosuppressive cells; ICI may help overcome these immunosuppressive effects. Therefore, the combination of ICI and RT has attracted attention in recent years. The therapeutic benefits of this combination therapy and its optimal regimen have not yet been determined through prospective studies. Therefore, this review article aimed to provide an overview of the current preclinical and clinical studies that illustrate the underlying mechanisms and explore the optimization of the RT regimen along with the ICI and RT combination sequence. We also analyzed ongoing prospective studies on ICI and RT combination therapies for metastatic UC. We noted that the tumor response to ICI and RT combination seemingly differs among cancer types. Thus, our findings highlight the need for well-designed prospective trials to determine the optimal combination of ICI and RT for locally advanced and metastatic UC.

Improving compliance with guidelines may lead to favorable clinical outcomes for patients with non-muscle-invasive bladder cancer: A retrospective multicenter study.

OBJECTIVES: Clinical guidelines recommend that patients with non-muscle-invasive bladder cancer (NMIBC) should be treated with appropriate adjuvant therapy. However, compliance with guideline recommendations is insufficient, and this may lead to unfavorable outcomes. We aimed to investigate the level of adherence to guideline recommendations in patients with NMIBC and evaluate the outcomes of those who did and did not receive guideline-recommended therapies. METHODS: We performed a retrospective analysis of patients with histologically diagnosed NMIBC. The percentage of patients with intermediate- and high-risk tumors who received adjuvant intravesical therapy or second transurethral resection (TUR) was calculated. Recurrence-free survival was assessed in patients who did and did not receive the therapies. We conducted a propensity score-matched analysis to compare outcomes between patients with intermediate-risk and T1 NMIBC who did and did not undergo guideline-recommended therapies. RESULTS: Overall, 1204 patients from the Tohoku Urological Evidence-Based Medicine Study Group and Kyoto University Hospital were included. Of patients with intermediate- and high-risk tumors, 91.0% and 74.0% did not receive maintenance bacillus Calmette-Guérin (BCG), respectively. In both groups, significantly better recurrence-free survival was found for patients treated with maintenance BCG. Among patients with T1 NMIBC, only 16.7% underwent guideline-recommended therapies, that is, a second TUR and maintenance BCG. Significantly greater recurrence-free survival was observed in patients who received guideline-recommended therapies compared with propensity-matched patients who did not. CONCLUSIONS: Guideline-recommended therapies may contribute to improvements in outcomes for patients with NMIBC, suggesting that improvements in adherence to clinical guidelines may lead to favorable outcomes.

Addition of docetaxel to S-1 results in significantly superior 5-year survival outcomes in Stage III gastric cancer: a final report of the JACCRO GC-07 study.

PURPOSE: A phase III trial comparing S-1 and docetaxel with S-1 alone as postoperative chemotherapy for pathologically Stage III gastric cancer was conducted and clarified the superiority of the doublet in terms of 3-year relapse-free survival as the primary endpoint (67.7% versus 57.4%, hazard ratio [HR] 0.715, 95% confidence interval [CI] 0.587-0.871; p = 0.0008). This final report analyzed 5-year survival outcomes along with the incidence and pattern of late recurrences. PATIENTS AND METHODS: Patients with histologically confirmed Stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. The same 912 patients who were evaluated for 3-year survival outcomes in the previous report were analyzed. RESULTS: Five-year overall survival rate of the S-1 plus docetaxel group (67.91%) was significantly superior to that in the S-1 group (60.27%; HR 0.752, 95% CI 0.613-0.922; p = 0.0059). The incidence of late recurrence at > 3 years after randomization was similar in both groups (7.3% versus 7.2%). Peritoneal dissemination was the most common pattern of late recurrence. Addition of docetaxel significantly suppressed relapse through the lymphatic (6.8% [95% CI 4.52-9.17] versus 15% [95% CI 11.76-18.30]; p < 0.0001) and hematogenous (10.2% [95% CI 7.37-12.94] versus 15.7% [95% CI 12.36-19.01]; p < 0.0137) pathways throughout the 5 years of follow-up. CONCLUSION: The survival benefit of postoperative chemotherapy with S-1 and docetaxel in terms of 5-year overall survival rate was confirmed for patients with pathologically Stage III gastric cancer, although late recurrences were not prevented.