A Systematic Review and Meta-analysis of the Impact of Local Therapies on Local Event Suppression in Metastatic Hormone-sensitive Prostate Cancer.

CONTEXT: It remains unclear to what extent the therapy of the primary local tumor, such as radical prostatectomy (RP) and radiation therapy (RT), improves overall survival in patients with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). However, data suggest a benefit of these therapies in preventing local events secondary to local tumor progression. OBJECTIVE: To evaluate the efficacy of adding local therapy (RP or RT) to systemic therapies, including androgen deprivation therapy, docetaxel, and/or androgen receptor axis-targeted agents, in preventing local events in mHSPC patients compared with systemic therapy alone (ie, without RT of the prostate or RP). EVIDENCE ACQUISITION: Three databases and meeting abstracts were queried in November 2023 for studies analyzing mHSPC patients treated with local therapy. The primary outcome of interest was the prevention of overall local events (urinary tract infection, urinary tract obstruction, and gross hematuria) due to local disease progression. Subgroup analyses were conducted to assess the differential outcomes according to the type of local therapy (RP or RT). EVIDENCE SYNTHESIS: Overall, six studies, comprising two randomized controlled trials, were included for a systematic review and meta-analysis. The overall incidence of local events was significantly lower in the local treatment plus systemic therapy group than in the systemic therapy only groups (relative risk [RR]: 0.50, 95% confidence interval [CI]: 0.28-0.88, p = 0.016). RP significantly reduced the incidence of overall local events (RR: 0.24, 95% CI: 0.11-0.52) and that of local events requiring surgical intervention (RR: 0.08, 95% CI: 0.03-0.25). Although there was no statistically significant difference between the RT plus systemic therapy and systemic therapy only groups in terms of overall local events, the incidence of local events requiring surgical intervention was significantly lower in the RT plus systemic therapy group (RR: 0.70, 95% CI: 0.49-0.99); local events requiring surgical intervention of the upper urinary tract was significantly lower in local treatment groups (RR: 0.60, 95% CI: 0.37-0.98, p = 0.04). However, a subgroup analysis revealed that neither RP nor RT significantly impacted the prevention of local events requiring surgical intervention of the upper urinary tract. CONCLUSIONS: In some patients with mHSPC, RP or RT of primary tumor seems to reduce the incidence of local progression and events requiring surgical intervention. Identifying which patients are most likely to benefit from local therapy, and at what time point (eg, after response of metastases), will be necessary to set up a study assessing the risk, benefits, and alternatives to therapy of the primary tumor in the mHSPC setting. PATIENT SUMMARY: Our study suggests that local therapy of the prostate, such as radical prostatectomy or radiotherapy, in patients with metastatic hormone-sensitive prostate cancer can prevent local events, such as urinary obstruction and gross hematuria.

Primary retroperitoneal lymph node dissection for clinical stage II seminoma: A systematic review and meta-analysis of safety and oncological effectiveness.

To evaluate the oncological outcomes and safety of primary retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) II seminomatous testicular germ cell tumor (TGCT). A literature search using PubMed, Scopus, and Cochrane Library was conducted on July 2023 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) guidelines. The pooled recurrence rate and treatment-related complications were calculated using a random effects model. Overall 8 studies published between 1997 and 2023 including a total of 355 patients were selected for systematic review and meta-analysis with the overall median follow-up of 38 months. The overall and infield recurrence rate were 0.14 (95% CI: 0.08-0.22) and 0.04 (95% CI: 0.00-0.11), respectively. The overall pooled rate of ≥ Clavien Dindo grade III complications was 0.04 (95% CI: 0.01-0.10); there was no significant heterogeneity (I^2 = 35.10%, P = 0.19). Antegrade ejaculation was preserved with the overall pooled rate of 0.98 (95% CI: 0.95-1.00); there was no significant heterogeneity on Chi-square and I2 tests (I^2 = 0.00%, P = 0.58). Primary RPLND is a safe and effective treatment option for patients with CS II seminomatous TGCT resulting highly promising cure rates combined with low treatment-associated adverse events, at medium-term follow-up. However, owing to the lack of comparative studies to the current standard of care and the limited follow-up, individual decision must be made with the informed patient in a shared decision process together with a multidisciplinary team.

Comparing the Performance of Digital Rectal Examination and Prostate-specific Antigen as a Screening Test for Prostate Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Although digital rectal examination (DRE) is recommended in combination with prostate-specific antigen (PSA) for detection of prostate cancer (PCa), there are limited data to support its use as a screening/early detection test. Our objective was to assess the diagnostic value of DRE in screening for early detection of PCa. METHODS: In August 2023, we queried the PubMed, Scopus, and Web of Science databases to identify prospective studies simultaneously investigating the diagnostic performance of DRE and PSA for PCa screening. The primary endpoints were the positive predictive value (PPV) and cancer detection rate (CDR) of DRE. Secondary endpoints included the PPV and CDR of both PSA alone and in combination with DRE. We conducted meta-regression analysis to compare the CDR and PPV of different screening strategies. This meta-analysis is registered on PROSPERO (CRD42023446940). KEY FINDINGS AND LIMITATIONS: We identified eight studies involving 85 738 participants, of which three were randomized controlled trials and five were prospective diagnostic studies, that reported the PPV and CDR of both DRE and PSA for the same cohort. Our analysis revealed a pooled PPV of 0.21 (95% confidence interval [CI] 0.13-0.33) for DRE, which is similar to the PPV of PSA (0.22, 95% CI 0.15-0.30; p = 0.9), with no benefit from combining DRE and PSA (PPV 0.19, 95% CI 0.13-0.26; p = 0.5). However, the CDR of DRE (0.01, 95% CI: 0.01-0.02) was significantly lower than that of PSA (0.03, 95% CI 0.02-0.03; p < 0.05) and the combination of DRE and PSA (0.03, 95% CI 0.02-0.04; p < 0.05). The screening strategy combining DRE and PSA was not different to that of PSA alone in terms of CDR (p = 0.5) and PPV (p = 0.5). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our comprehensive review and meta-analysis indicates that both as an independent test and as a supplementary measure to PSA for PCa detection, DRE exhibits a notably low diagnostic value. The collective findings from the included studies suggest that, in the absence of clinical symptoms and signs, DRE could be potentially omitted from PCa screening and early detection strategies. PATIENT SUMMARY: Our review shows that the screening performance of digital rectal examination for detection of prostate cancer is not particularly impressive, suggesting that it might not be necessary to conduct this examination routinely.

Efficacy and safety of immune checkpoint inhibitors for patients with prostate cancer: a systematic review and meta-analysis.

Immunotherapy has revolutionized the treatment paradigm of many cancers, however, its effectiveness in prostate cancer patients is still under question. In the present systematic review and meta-analysis, we sought for assessing the efficacy and safety of Immune checkpoint inhibitors (ICIs) in patients with prostate cancer. PubMed, Scopus, Web of Science, and EMBASE databases were searched on Aguste 19, 2022. Thirty five studies met the eligibility criteria. The median overall survival (mOS) of all treatments was 14.1 months, with the longest and shortest mOS was seen among patients who received anti-CTLA-4 monotherapy and anti-PD-1/PD-L1+anti-CTLA-4 regimen at 24.9 and 9.2 months, respectively. Noteworthy, all types of adverse events had the lowest incidence in the anti-PD-1/PD-L1 monotherapy group. Considering the ICI monotherapy regimens, we found that fatigue, diarrhea, and infusion reaction had the highest incidence rates. Future studies evaluating the efficacy and safety of novel combination therapies with ICIs are warranted.

Metastatic Organotropism Differential Treatment Response in Urothelial Carcinoma: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

CONTEXT: The optimal therapeutic agent with respect to metastatic sites is unclear in advanced urothelial carcinoma (UC). OBJECTIVE: To investigate the metastatic organotropism differential treatment response in patients with advanced or metastatic UC. EVIDENCE ACQUISITION: A systematic search and network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The primary endpoints of interest were the objective response rate, overall survival (OS), and progression-free survival with respect to different metastatic sites. EVIDENCE SYNTHESIS: Twenty-six trials comprising 9082 patients met our eligibility criteria, and a formal NMA was conducted. Durvalumab plus tremelimumab as first-line systemic therapy was significantly associated with better OS than chemotherapy in visceral metastasis (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.67-0.98). Pembrolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with visceral metastasis (HR 0.75, 95% CI 0.60-0.95). Atezolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with liver metastasis (in the population of >5% of tumor-infiltrating immune cells) and lymph node metastasis (HR 0.51, 95% CI 0.28-0.96, and HR 0.59, 95% CI 0.37-0.96, respectively). CONCLUSIONS: Administration of immune-oncology treatments with respect to metastatic sites in patients with advanced or metastatic UC might have a positive impact on survival outcomes in both the first- and the second-line setting. Nevertheless, further investigations focusing on metastatic organotropism differential response with reliable oncological outcomes are needed to identify the optimal management strategy for these patients. PATIENT SUMMARY: Although the supporting evidence for oncological benefits of therapeutic systemic agents with respect to metastatic sites is not yet strong enough to provide a recommendation in advanced or metastatic urothelial carcinoma, clinicians may take into account tumor organotropism only in discussion with the patient fully informed on the optimal treatment decision to be taken.

A Systematic Review and Meta-Analysis of Clinicopathologic Factors Predicting Upper Urinary Tract Recurrence After Radical Cystectomy for Urothelial Bladder Cancer.

To identify risk factors for upper urinary tract recurrence (UUTR) in patients treated with radical cystectomy (RC) for urothelial bladder carcinoma (UBC). The PubMed, Web of Science, and Cochrane Library were searched on March 2022 to identify relevant studies according to the Preferred Reporting Items for Systematic Review (PRISMA) statement. We included studies that provided multivariate logistic regression analyses. The pooled UUTR rate was calculated using a fixed effect model. We identified 235 papers, of which seven and 6 articles, comprising a total of 8981 and 8404 UBC patients, were selected for qualitative and quantitative analyses, respectively. Overall, 418 (4.65%) patients were diagnosed with UUTR within a median time of 1.4 to 3.1 years after RC. Risk factors for UUTR were surgical margin (hazard ratio [HR] 3.41, 95% confidence interval [CI] 2.59-4.49, P < .00001), preoperative hydronephrosis (HR: 1.74, 95% CI: 1.25-2.43, P = .001), ureteral margin (HR: 4.34, 95% CI: 2.75-6.85, P < .00001), and pT stage (HR: 2.69, 95% CI: 1.37-5.27, P < .004). Incorporation of established risk factors into a clinical prediction model might aid in the decision-making process regarding the intensity and type of surveillance protocols after RC as well as help determine the pretest probability of UUTR.

Preservation of male fertility in patients undergoing pelvic irradiation.

As the number of cancer survivors increases, so does the demand for preserving male fertility after radiation. It is important for healthcare providers to understand the pathophysiology of radiation-induced testicular injury, the techniques of fertility preservation both before and during radiation, and their role in counseling patients on the risks to their fertility and the means of mitigating these risks. Impaired spermatogenesis is a known testicular toxicity of radiation in both the acute and the late settings, as rapidly dividing spermatogonial germ cells are exquisitely sensitive to irradiation. The threshold for spermatogonial injury and subsequent impairment in spermatogenesis is ~ 0.1 Gy and the severity of gonadal injury is highly dose-dependent. Total doses < 4 Gy may allow for recovery of spermatogenesis and fertility potential, but with larger doses, recovery may be protracted or impossible. All patients undergoing gonadotoxic radiation therapy should be counseled on the possibility of future infertility, offered the opportunity for semen cryopreservation, and offered referral to a fertility specialist. In addition to this, every effort should be made to shield the testes (if not expected to contain tumor) during therapy.

Association of Dietary Approaches to Stop Hypertension diet and risk of bladder cancer: A case-control study.

OBJECTIVE: The Dietary Approaches to Stop Hypertension (DASH) diet is rich in recommended foods that are inversely associated with bladder cancer (BC) risk. The main objective of this study was to investigate the association between adherence to DASH diet and the risk of BC among Iranian adults. METHOD: This study included 103 BC cases and 200 controls. The controls were patients who were hospitalised for acute non-neoplastic diseases. DASH scores were computed from dietary intake assessed by a previously validated food frequency questionnaire. RESULTS: After controlling for potential confounders, participants in the highest quintile of DASH (compared to the lowest quintile) had 84% lower BC risk (OR = 0.16; 95%CI: 0.05-0.45; p trend = 0.001). Among the DASH components, significant negative associations were observed between low fat dairy and whole grains intake with BC (p value < 0.05). A positive relation was observed for sodium, nuts and legumes, and sweetened beverages (p value < 0.05). CONCLUSION: The results of this study suggested that adherence to DASH might be associated with reduced risk of BC. These findings could be used to develop evidence-based recommendations for the prevention of BC.

Association of Recommended and Non-Recommended Food Score and Risk of Bladder Cancer: A Case-Control Study.

Bladder cancer (BC) is the ninth most common cancer in the world. Dietary patterns and diet quality could reduce exposure to carcinogenic factors postulated to increase the risk of BC. The main objective of this study was to investigate the associations of Recommended Food Score (RFS) and Non-Recommended Food Score (n-RFS) with the risk of BC among Iranian adults.This is a hospital-based case-control study, conducted at three referral hospitals in Tehran, the capital of Iran. Cases consisted of 103 histologically confirmed BC patients, aged greater than 45 years. Age-matched controls (n = 200) were selected from the same hospital where cases were recruited. Controls were patients with non-neoplastic diseases that are not related to smoking, or long-term diet modification. Dietary intake was assessed by a 168-item Food Frequency Questionnaire (FFQ), which was validated in Iran. Logistic regression tests were used to estimate the relationship between RFS and n-RFS with BC.The risk of BC decreased by 69% (OR = 0.31; 95% CI:0.13-0.71) among participants belonging to the highest compared with the lowest quartile of RFS. After adjusting for age, sex, smoking, and total energy, a significant inverse trend was observed between the risk of BC and quartile of RFS. Regarding the n-RFS, also expressed as quartiles, subjects in the fourth quartile were at 2.7 times higher risk of having BC compared to participants in the first quartile (OR = 2.7; 95%CI: 1.07-6.78).The findings of this study suggested that, adherence to RFS decreased the risk of BC. Additionally, a higher score of n-RFS may lead to an increased risk of BC. These findings could be used to develop evidence-based recommendations for the prevention of BC in Iran.

Association of the Healthy Nordic Food Index with risk of bladder cancer: a case-control study.

BACKGROUND: Bladder cancer (BC) is the ninth recurrent neoplasm in the world. In Iran, incidence of BC is the third most common among men. Few dietary patterns are related to reduced carcinogenesis and consequently are amenable to modification in order to reduce the BC risk. Adherence to the traditional Nordic diet, as measured by the Healthy Nordic Food Index (HNFI), have shown a beneficial effect on chronic disease prevention, including cancer. The principal objective of this study was to investigate the association between HNFI and the odds of BC in a case-control study, in Iran. METHOD: The present case-control study was performed on 100 eligible cases and 200 controls of patients ≥45 years old referred to three referral hospitals in Tehran. Dietary intakes are assessed by a valid 168-item food frequency questionnaire (FFQ). The relationship between HNFI and BC is estimated using the logistic regression tests. RESULTS: The average age of cases and control were 65.41 and 61.31 years, respectively. After controlling for potential confounders (age, smoke, total energy, and sex), participants in the highest tertile of HNFI (compared to the lowest tertile) have 83% lower BC risk (OR = 0.17; 95%CI = 0.07-0.42). Based on an independent assessment of HNFI component and BC risk, a significant negative association was observed for fish intake (OR = 0.30; 95%CI = 0.15- 0.60) and whole-grain bread intake (OR = 0.33; 95%CI = 0.17-0.63). CONCLUSION: The findings of this study suggested that adherence to traditional Nordic diet could decrease the risk of BC. Of the elements of this diet, fish and whole-grain bread consumption seemed to decrease the odds of BC. Such findings ought to be considered in the development of evidence-base intervention for BC prevention in the country.

A Prospective Study on [68Ga]-PSMA PET/CT Imaging in Newly Diagnosed Intermediate- and High-Risk Prostate Cancer.

OBJECTIVES: Prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) is an emerging modality to detect metastatic disease in patients with prostate cancer (PCa). This prospective study aimed to evaluate the role of [68Ga]-PSMA PET/CT in the initial workup of intermediate and high-risk PCa. METHODS: Twenty-five patients with newly transrectal ultrasound biopsy-proven, untreated intermediate- and high-risk PCa (mean age, 68.5±6.2 years; range 55-83 years) were enrolled in this prospective study between September 2018 and June 2020 and underwent a [68Ga]-PSMA PET/CT examination. All images were analyzed both visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax) of the primary prostatic tumor and metastatic lesions. The diagnostic sensitivity of [68Ga]-PSMA PET/CT for the diagnosis of PCa was established by histopathology as the reference standard. The associations between SUVmax of the primary tumors and prostate-specific antigen (PSA) levels, Gleason scores (GSs), and metastatic extent of the disease were studied. RESULTS: All patients had a positive [68Ga]-PSMA PET/CT exam. Seventeen patients (58%) showed [68Ga]-PSMA avidity in both prostate lobes and 8 (32%) had unilateral uptake. SUVmax in the primary tumor significantly correlated with serum PSA values (r=0.57, P=0.003). PSMA PET/CT depicted regional lymph node metastases in 32% of patients, distant lymph node metastases in 20%, osseous metastases in 16% and pulmonary metastases in 8% of patients. Sixty percent of PSMA-positive bone metastases and 21.4% of intraprostatic tumoral lesions were missed on the contemporaneous bone scintigraphy and magnetic resonance imaging, respectively. CONCLUSION: [68Ga]-PSMA PET/CT shows promise as a valuable imaging modality with high diagnostic sensitivity in the setting of intermediate and high-risk PCa. Moreover, the SUVmax of the primary tumor has a positive correlation with PSA levels at the time of the scan.

Prognostic Impact of Different Gleason Patterns on Biopsy Within Grade Group 4 Prostate Cancer.

BACKGROUND: Grade group (GG) 4 prostate cancer (PC) is considered a single entity; however, there are questions regarding prognostic heterogeneity. This study assessed the prognostic differences among various Gleason scores (GSs) classified as GG 4 PC on biopsy before radical prostatectomy (RP). METHODS: We conducted a multicenter retrospective study, and a total of 1791 patients (GS 3 + 5: 190; GS 4 + 4: 1557; and GS 5 + 3: 44) with biopsy GG 4 were included for analysis. Biochemical recurrence (BCR)-free survival, cancer-specific survival, and overall survival were analyzed using the Kaplan-Meier method and the log-rank test. Logistic regression analysis was performed to identify factors associated with high-risk surgical pathologic features. Cox regression models were used to analyze time-dependent oncologic endpoints. RESULTS: Over a median follow-up of 75 months, 750 patients (41.9%) experienced BCR, 146 (8.2%) died of any causes, and 57 (3.2%) died of PC. Biopsy GS 5 + 3 was associated with significantly higher rates of GS upgrading in RP specimens than GS 3 + 5 and GS 4 + 4. On multivariable analysis adjusted for clinicopathologic features, different GSs within GG 4 were significantly associated with BCR (p = 0.03) but not PC-specific or all-cause mortality. Study limitations include the lack of central pathological specimen evaluation. CONCLUSIONS: Patients with GG 4 at biopsy exhibited some limited biological and clinical heterogeneity. Specifically, GS 5 + 3 had an increased risk of GS upgrading. This can help individualize patients' counseling and encourage further study to refine biopsy specimen-based GG classification.

Fibroblast growth factor receptor: A systematic review and meta-analysis of prognostic value and therapeutic options in patients with urothelial bladder carcinoma.

To evaluate the oncologic prognostic value of fibroblast growth factor receptor (FGFR) and to assess the safety and efficacy of its inhibitors in patients with urothelial bladder carcinoma. A literature search using PubMed, Scopus, and Cochrane Library was conducted on June 2020 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The pooled recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS) were calculated using a fixed or random effects model in patients with nonmuscle invasive bladder cancer (NMIBC). Overall, 62 studies comprising 9,229 patients were eligible and included in this systematic review and meta-analysis. Both FGFR3 mutation and protein overexpression were significantly associated with RFS, PFS, CSS, and overall survival. FGFR3 mutation was associated with worse RFS and better PFS (pooled hazard ratio: 1.30; 95% confidence interval: 1.08-1.57, and pooled hazard ratio: 0.62; 95% confidence interval: 0.42-0.92, respectively) in patients with NMIBC. In 11 studies reporting on the response to FGFR inhibitors, complete response rates, disease control rates, and overall response rate of 0% to 8%, 59.3% to 64.2%, and 40% were reported for dovitinib, infigratinib, and erdafitinib, respectively. Based on this study, FGFR3 mutation is a statistically significant prognostic factor for RFS in NMIBC. FGFR inhibitors have measurable benefit in patients with advanced and metastatic urothelial carcinoma. However, the results of ongoing RCTs and future well-designed studies are awaited to capture the differential biologic and clinical behavior of tumors harboring FGFR while helping to identify those who are most likely to benefit from FGFR inhibitors.

Prognostic role of the systemic immune-inflammation index in upper tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

PURPOSE: To investigate the prognostic role of the preoperative systemic immune-inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS). RESULTS: Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis. CONCLUSIONS: Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.

Value of tumour-infiltrating immune cells in predicting response to intravesical BCG in patients with non-muscle-invasive bladder cancer: a systematic review and meta-analysis.

OBJECTIVE: To investigate the predictive value of tumour-infiltrating immune cells (TIICs) on oncological outcomes and response to BCG treatment in patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A systematic review and meta-analysis was performed using PubMed, Scopus and the Cochrane Library in July 2020 to identify relevant studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The pooled recurrence-free survival (RFS) rate was calculated using a fixed-effect model. RESULTS: We retrieved 15 studies (including 791 patients) evaluating the effect of TIICs on oncological outcomes in patients with NMIBC treated with intravesical BCG. TIICs were reported to be a significant predictor of oncological outcomes and response to BCG treatment in 10 studies. Tumour-associated macrophages were associated with worse RFS (pooled hazard ratio 2.30, 95% confidence interval 1.64-3.22). CONCLUSIONS: Based on these data, TIICs are significant predictors of RFS and response to BCG treatment in patients with NMIBC; therefore, incorporation of TIICs into risk stratification models may help patients and physicians in the clinical decision-making process in order to achieve the maximum possible benefit from BCG treatment.

The value and limitations of urothelial bladder carcinoma molecular classifications to predict oncological outcomes and cancer treatment response: A systematic review and meta-analysis.

AIM: To evaluate the predictive value of molecular subtypes on oncological outcomes and response to cancer treatment in patients with urothelial bladder carcinoma (UBC). MATERIALS AND METHODS: A literature search using PubMed, Scopus, and Cochrane Library was conducted on April 2020 to identify relevant studies according to the preferred reporting items for systematic review and meta-analysis guidelines. The pooled overall survival (OS), cancer-specific survival (CSS), and progression-free survival were calculated using a fixed or random effects model. RESULTS: We identified 66 studies (including 21,447 molecular subtype records) evaluating the impact of molecular classification on oncologic outcomes in patients with UBC. We found significant association of different molecular subtypes with OS, CSS, progression-free survival, recurrence-free survival, and response to treatment. Totally, 11 studies were included in the meta-analysis. Basal group and NE-like subtypes were associated with worse OS (pooled HR: 1.78, 95%CI: 1.49-2.12, and pooled HR: 2.67, 95%CI: 1.08-6.60, respectively) in patients with muscle invasive bladder cancer. Luminal group was also associated with worse CSS (pooled HR of 3.67, 95%CI: 2.19-6.14). CONCLUSIONS: Based on these data, UBC molecular classifications are significant predictors of oncological outcomes and identify patients who are most likely to benefit from intensified or different therapies. The optimal consensus on molecular classification remains to be verified in well-designed prospective studies to allow precise prognostic and predictive value assessment.

Metastasis of a prostate adenocarcinoma to mandible: A case report and review of literature.

Dentists and physicians should include oral metastases originating from prostate adenocarcinoma as a rare differential diagnosis of jaw lesions that can produce periosteal reactions in the radiographic features such as osteosarcoma.

Prognostic value of T1 substaging on oncological outcomes in patients with non-muscle-invasive bladder urothelial carcinoma: a systematic literature review and meta-analysis.

PURPOSE: To evaluate the prognostic value of substaging on oncological outcomes in patients with T (or pT1) urothelial carcinoma of the bladder. METHODS: A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on March 2019 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The pooled disease recurrence (DR) and disease progression (DP) rate in T1(or pT1) patients were calculated using a fixed or random effects model. RESULTS: Overall 36 studies published between 1994 and 2018 including a total of 6781 bladder cancer patients with T1(or pT1) stage were selected for the systematic review and meta-analysis. Twenty-nine studies reported significant association between tumor infiltration depth or muscularis mucosa (MM) invasion and oncological outcomes. Totally 12 studies were included in the meta-analysis. MM invasion (T1a/b/c [or pT1a/b/c] or T1a/b [or pT1a/b] substaging system) was associated with DR (pooled HR: 1.23, 95%CI: 1.01-1.49) and DP (pooled HR: 2.61, 95%CI: 1.61-4.23). Tumor infiltration depth (T1 m/e [or pT1 m/e] substaging system) was also associated with DR (pooled HR: 1.49, 95%CI: 1.11-2.00) and DP (pooled HR: 3.29, 95%CI: 2.39-4.51). CONCLUSIONS: T1(or pT1) substaging in patients with bladder cancer is of prognostic value as it is associated with oncologic outcomes. Inclusion of this factors into the clinical decision-making process of this heterogeneous tumor may improve outcomes, while avoiding over- and under-treatment for T1(or pT1) bladder cancer.

Oncological safety of testosterone replacement therapy in prostate cancer survivors after definitive local therapy: A systematic literature review and meta-analysis.

AIM: To evaluate the association between testosterone replacement therapy (TRT) in prostate cancer (CaP) patients who underwent definitive local therapy with curative intent with biochemical recurrence (BCR). MATERIALS AND METHODS: A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on November 2018 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta Analysis guidelines. The pooled BCR rate in CaP men treated with TRT after definitive local therapy with curative intent was calculated using a random effects model. RESULTS: Twenty-one studies were eligible. The overall pooled BCR rate was 0.01 (95%CI 0.00-0.02) suggesting a lack of association between TRT and BCR; there was no heterogeneity among included studies (I2 = 24.34%, P = 0.15). In subgroup analyses, pooled BCR rates were 0.00 (95%CI 0.00-0.02) in patients treated with radical prostatectomy and 0.02 (95%CI 0.00-0.04) in patients treated with external beam radiation therapy, brachytherapy, cryotherapy, or high intensity focused ultrasound; there was no heterogeneity in the subgroup analyses (I2 = 19.88%, P = 0.18). CONCLUSIONS: In this systematic review and meta-analysis, we did not observe higher rate of BCR after TRT for nonmetastatic CaP patients after definitive local therapy. Based on these data, others and we have outlined a phase I/II trial assessing the safety and benefits of TRT in select men with secondary symptomatic hypogonadism who have no active disease after definitive local CaP therapy with curative intent.

Serogroup distribution, diversity of exotoxin gene profiles, and phylogenetic grouping of CTX-M-1- producing uropathogenic Escherichia coli.

The emergence of CTX-M-1 producing Uropathogenic Escherichia coli (UPEC) has become a serious challenge. In addition to antimicrobial resistance, a number of virulence factors have been shown. Therefore, this study was designed to determine the prevalence of O- serogroups, phylogenetic groups, exotoxin genes, and antimicrobial resistance properties of CTX-M-1- producing UPEC. A total of 248 UPEC isolates were collected. The antibiotic resistance was performed, and PCR was used to detect the blaCTX-M1, exotoxins, serogroups and phylogroups of UPEC. Of 248 isolates, 95 (38.3%) harbored blaCTX-M-1. Of them, serogroups O1 and O25 were predominant, accounting for 20% and 13.7%, respectively. The hlyA was the dominant exotoxin gene (32.6%), followed by sat (28.4%), vat (22.1%), cnf (13.7%), picU (8.4%), and cdt (2.1%). The hlyA gene was significantly associated with pyelonephritis (P = 0.003). Moreover, almost half of the isolates (45.4%) belonged to phylogenetic group B2. Most of exotoxin genes were present in significantly higher proportions in group B2 isolates except cdt gene (P < 0.05). All of the isolates were susceptible to imipenem, nitrofurantoin, and fosfomycin. The CTX-M-1-producing UPEC strains causing nosocomial infections are more likely to harbor certain exotoxin genes, raising the possibility that this increase in virulence genes may result in an increased risk of complicated UTI.