Application of Internet-based multidisciplinary management in patients with genitourinary cancers in China: A brief introduction to a new model of healthcare service for cancer survivors during COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has triggered multiple global healthcare system crises. Apart from the pandemic itself, the travel restriction and social distance policy for the purpose of epidemic control has cast a shadow on the management of cancer survivors. Cancer survivors suffered a double blow from both the epidemic and cancer. To deal with the challenge, we explored a new Internet-based patient management model. This model has overcome the limitation of time and space and thus can help oncologists to provide remote multidisciplinary healthcare services for cancer survivors. These patients can get high-quality cancer management from multidisciplinary experts without too much transportation. This model has been applied in patients with genitourinary cancers and proved to be effective and efficient. Our study demonstrated that more patients benefited from this model during the pandemic of COVID-19, especially in those affected heavily by COVID-19. These results suggested that it can also give insight into the management of other cancer survivors in China. Given the long-term impact of the COVID-19 pandemic, we would like to introduce our new model of healthcare service and the application of Internet-based multidisciplinary management to our global peers and medical industries to help their cancer survivors who are delayed in treatment due to the COVID-19 pandemic.

Prostate Cancer Screening Using Prostate-Specific Antigen Tests in a High-Risk Population in China: A Cost-Utility Analysis.

BACKGROUND: Both National Comprehensive Cancer Network and Chinese guidelines recommend beginning prostate-specific antigen (PSA) screening for men aged 50 years or 45 years with a family history because they were at a higher risk of developing prostate cancer. Several model-based economic evaluations of PSA screening studies have been conducted, but with little evidence from China. OBJECTIVE: The aim of this study was to conduct an economic evaluation of the cost-utility of PSA-based prostate cancer screening in Chinese men. METHODS: We developed a decision-tree and Markov model in Excel (Microsoft Corp, Redmond, Washington) to compare 2 strategies that can be used to detect prostate cancer: PSA-based screening followed by a biopsy, and non-PSA screening. We assumed that the patients would repeat screening in subsequent years if their first-year PSA value was higher than 4.0 ng/mL. The model adopted health care system perspective and lifetime horizon. Screening efficacy, cost, utility, and long-term survival of prostate cancer were retrieved from published literature and physician surveys. Both quality-adjusted life year and costs were discounted at an annual rate of 3.5%. Uncertainty was assessed by 1-way and probabilistic sensitivity analyses. Our model also calculated the risk-to-benefit ratio as the ratio of overdiagnosis (biopsy without diagnosed) to prostate cancer-related deaths prevented in different age groups. RESULTS: The results suggested that PSA-based screening was cost-effective compared with no PSA screening, with an incremental cost-utility ratio of ¥11,381 ($1821/€1480) per quality-adjusted life year. This value was less than the threshold of 1-time gross domestic product per capita in China (ie, ¥70,892 [$11,343/€9216]). Sensitivity analyses confirmed the robustness of the results. The risk-to-benefit ratios of the 50 to 65 years and the 65 to 80 years age groups were 1.3 and 2.8, respectively. CONCLUSIONS: PSA-based prostate cancer screening appears to be cost-effective in some high-risk Chinese men. PSA screening (PSA testing followed by magnetic resonance imaging and biopsy if positive) can be recommended for Chinese men aged 50 to 65 years because this approach had the lowest risk-to-benefit ratio. The approach should be further adapted based on future updated data. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX)© 2022 Elsevier HS Journals, Inc.

Genetic polymorphisms at 19q13.33 are associated with [-2]proPSA (p2PSA) levels and provide additional predictive value to prostate health index for prostate cancer.

BACKGROUND: Prostate health index (phi), a derivative of [-2]proPSA (p2PSA), has shown better accuracy than prostate-specific antigen (PSA) in prostate cancer (PCa) detection. The present study was to investigate whether previously identified PSA-associated single nucleotide polymorphisms (SNPs) influence p2PSA or phi levels and lead to potential clinical utility. METHODS: We conducted an observational prospective study with 2268 consecutive patients who underwent prostate biopsy in three tertiary medical centers from August 2013 to March 2019. Genotyping data of the 46 candidate genes with a ± 100 kb window were tested for association with p2PSA and phi levels using linear regression. Multivariable logistic regression models were performed and internally validated using repeated tenfold cross-validation. We further calculated personalized phi cutoff values based on the significant genotypes. Discriminative performance was assessed using decision curve analysis and net reclassification improvement (NRI) index. RESULTS: We detected 11 significant variants at 19q13.33 which were p2PSA-associated independent of PCa. The most significant SNP, rs198978 in KLK2 (Pcombined = 5.73 × 10-9 ), was also associated with phi values (Pcombined = 3.20 × 10-6 ). Compared to the two commonly used phi cutoffs of 27.0 and 36.0, the personalized phi cutoffs had a significant NRI for PCa ranged from 5.23% to 9.70% among men carrying variant types (all p < .01). CONCLUSION: Rs198978, is independently associated with p2PSA values, and can improve the diagnostic ability of phi for PCa using personalized cutoff values.

Prostate volume does not provide additional predictive value to prostate health index for prostate cancer or clinically significant prostate cancer: results from a multicenter study in China.

To evaluate whether prostate volume (PV) would provide additional predictive utility to the prostate health index (phi) for predicting prostate cancer (PCa) or clinically significant prostate cancer, we designed a prospective, observational multicenter study in two prostate biopsy cohorts. Cohort 1 included 595 patients from three medical centers from 2012 to 2013, and Cohort 2 included 1025 patients from four medical centers from 2013 to 2014. Area under the receiver operating characteristic curves (AUC) and logistic regression models were used to evaluate the predictive performance of PV-based derivatives and models. Linear regression analysis showed that both total prostate-specific antigen (tPSA) and free PSA (fPSA) were significantly correlated with PV (all P < 0.05). [-2]proPSA (p2PSA) was significantly correlated with PV in Cohort 2 (P< 0.001) but not in Cohort 1 (P= 0.309), while no significant association was observed between phi and PV. When combining phi with PV, phi density (PHID) and another phi derivative (PHIV, calculated as phi/PV0.5) did not outperform phi for predicting PCa or clinically significant PCa in either Cohort 1 or Cohort 2. Logistic regression analysis also showed that phi and PV were independent predictors for both PCa and clinically significant PCa (all P < 0.05); however, PV did not provide additional predictive value to phi when combining these derivatives in a regression model (all models vs phi were not statistically significant, all P > 0.05). In conclusion, PV-based derivatives (both PHIV and PHID) and models incorporating PV did not improve the predictive abilities of phi for either PCa or clinically significant PCa.

Incorporating non-biological factors into the TNM staging system for better prognostication and decision-making in testicular cancer.

BACKGROUND: We combined county-level socioeconomic status (SES), marital status and insurance status to introduce NBF-stage, which were further incorporated into the American Joint Committee on Cancer (AJCC) TNM staging system to generate an integrated staging system for better prognostication and decision-making for testicular cancer patients. METHODS: 15,324 eligible patients diagnosed with primary testicular cancer between January 1, 2007 and December 31, 2015 were strictly selected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent survival predictors were determined based on Cox proportional hazards model. The Kaplan-Meier survival curves were conducted to describe the difference in predicting survival probability and the Multivariate Cox proportion hazard regression analyses were established to compare the cancer-specific survival (CSS) and overall survival (OS) difference among NBF stages or NBF-TNM subgroups. RESULTS: County-level SES, marital status and insurance status were independent prognostic non-biological factors (NBFs) in our study (P < 0.05). NBF-stage (combination of SES, marital status, and insurance status) was also an independent survival predictor in TC (P < 0.05). NBF1 patients had 167% increased risk of cancer-specific mortality (CSM) as compared to NBF0 patients in testicular cancer (P < 0.01). And NBF0 patients all had a better CSS as compared to NBF1 patients of the same TNM stage both in seminoma and non-seminomatous germ cell tumor (P < 0.05). CONCLUSIONS: Incorporation of NBFs into AJCC TNM staging system in testicular cancer would potentially impact treatment decisions where treatments would not be rendered for a typically curable cancer with multi-modal therapy.

Management of patients with advanced prostate cancer in the Asia Pacific region: 'real-world' consideration of results from the Advanced Prostate Cancer Consensus Conference (APCCC) 2017.

OBJECTIVE: The Asia Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2018) brought together 20 experts from 15 APAC countries to discuss the real-world application of consensus statements from the second APCCC held in St Gallen in 2017 (APCCC 2017). FINDINGS: Differences in genetics, environment, lifestyle, diet and culture are all likely to influence the management of advanced prostate cancer in the APAC region when compared with the rest of the world. When considering the strong APCCC 2017 recommendation for the use of upfront docetaxel in metastatic castration-naïve prostate cancer, the panel noted possible increased toxicity in Asian men receiving docetaxel, which would affect this recommendation in the APAC region. Although androgen receptor-targeting agents appear to be well tolerated in Asian men with metastatic castration-resistant prostate cancer, access to these drugs is very limited for financial reasons across the region. The meeting highlighted that cost and access to contemporary treatments and technologies are key factors influencing therapeutic decision-making in the APAC region. Whilst lower cost/older treatments and technologies may be an option, issues of culture and patient or physician preference mean, these may not always be acceptable. Although generic products can reduce cost in some countries, costs may still be prohibitive for lower-income patients or communities. The panellists noted the opportunity for a coordinated approach across the APAC region to address issues of access and cost. Developments in technologies and treatments are presenting new opportunities for the diagnosis and treatment of advanced prostate cancer. Differences in genetics and epidemiology affect the side-effect profiles of some drugs and influence prescribing. CONCLUSIONS: As the field continues to evolve, collaboration across the APAC region will be important to facilitate relevant research and collection and appraisal of data relevant to APAC populations. In the meantime, the APAC APCCC 2018 meeting highlighted the critical importance of a multidisciplinary team-based approach to treatment planning and care, delivery of best-practice care by clinicians with appropriate expertise, and the importance of patient information and support for informed patient choice.

A Multicentre Evaluation of the Role of the Prostate Health Index (PHI) in Regions with Differing Prevalence of Prostate Cancer: Adjustment of PHI Reference Ranges is Needed for European and Asian Settings.

Asians have a lower incidence of prostate cancer (PC). We compared the performance of the Prostate Health Index (PHI) for 2488 men in different ethnic groups (1688 Asian and 800 European men from 9 sites) with PSA 2-20ng/ml and PHI test and transrectal ultrasound-guided biopsy results available. Of these, 1652 men had PSA 2-10ng/ml and a normal digital rectal examination and underwent initial biopsy. The proportions of PC (Gleason ≥6) and higher-grade PC (HGPC, Gleason ≥7) across different PHI ranges were compared. The performance of PSA and PHI was compared using the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA). Among Asian men, HGPC would be diagnosed in 1.0%, 1.9%, 13%, and 30% of men using PHI thresholds of <25, 25-35, 35-55, and >55, respectively. At 90% sensitivity for HGPC (PHI >30), 56% of biopsies and 33% of Gleason 6 PC diagnoses could have been avoided. Among European men, HGPC would be diagnosed in 4.1%, 4.3%, 30%, and 34% of men using PHI thresholds of <25, 25-35, 35-55, and >55, respectively. At 90% sensitivity for HGPC (PHI >40), 40% of biopsies and 31% of Gleason 6 PC diagnoses could have been avoided. AUC and DCA confirmed the benefit of PHI over PSA. The benefit of PHI was also seen at repeat biopsy (n=397) and for PSA 10-20ng/ml (n=439). PHI is effective in cancer risk stratification for both European and Asian men. However, population-specific PHI reference ranges should be used. PATIENT SUMMARY: The Prostate Health Index (PHI) blood test helps to identify individuals at higher risk of prostate cancer among Asian and European men, and could significantly reduce unnecessary biopsies and overdiagnosis of prostate cancer. Different PHI reference ranges should be used for different ethnic groups.

Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC).

PURPOSE: Upper-tract urothelial carcinoma (UTUC) is a relatively uncommon disease with limited available evidence on specific topics. The purpose of this article was to review the previous literature to summarize the current knowledge about UTUC epidemiology, diagnosis, preoperative evaluation and prognostic assessment. METHODS: Using MEDLINE, a non-systematic review was performed including articles between January 2000 and February 2016. English language original articles, reviews and editorials were selected based on their clinical relevance. RESULTS: UTUC accounts for 5-10 % of all urothelial cancers, with an increasing incidence. UTUC and bladder cancer share some common risk factors, even if they are two different entities regarding practical, biological and clinical characteristics. Aristolochic acid plays an important role in UTUC pathogenesis in certain regions. It is further estimated that approximately 10 % of UTUC are part of the hereditary non-polyposis colorectal cancer spectrum disease. UTUC diagnosis remains mainly based on imaging and endoscopy, but development of new technologies is rapidly changing the diagnosis algorithm. To help the decision-making process regarding surgical treatment, extent of lymphadenectomy and selection of neoadjuvant systemic therapies, predictive tools based on preoperative patient and tumor characteristics have been developed. CONCLUSIONS: Awareness regarding epidemiology, diagnosis, preoperative evaluation and prognostic assessment changes is essential to correctly diagnose and manage UTUC patients, thereby potentially improving their outcomes.

Assessment of survival of patients with metastatic clear cell renal cell carcinoma after radical cytoreductive nephrectomy versus no surgery: a seer analysis.

PURPOSES: To examine the factors related to the choice of cytoreductive nephrectomy (CN) for patients with metastatic clear cell renal cell carcinoma (mCCRCC), and compare the population-based survival rates of patients treated with or without surgery in the modern targeted therapy era. MATERIALS AND METHODS: From 2006 to 2009, patients with mCCRCC were identified from SEER database. The factors that affected patients to be submitted to CN were examined and propensity scores for each patient were calculated. Then patients were matched based upon propensity scores. Univariable and multivariable cox regression models were used to compare survival rates of patients treated with or without surgery. Finally, sensitivity analysis for the cox model on a hazard ratio scale was performed. RESULTS: Age, race, tumor size, T stage and N stage were associated with nephrectomy univariablely. After the match based upon propensity scores, the 1-, 2-, and 3-year cancer-specific survival rate estimates were 45.1%, 27.9%, and 21.7% for the no-surgery group vs 70.6%, 52.2%, and 41.7% for the surgery group, respectively (hazard ratio 0.42, 95%CI: 0.35-0.52, log-rank P<0.001). In multivariable Cox proportional hazard regression model, race, T stage, N stage and median household income were significantly associated with survival. Sensitivity analysis on a hazard ratio scale indicated that the hazard ratio might be above 1.00 only when the unknown factor had an opposite effect on survival which was 3-fold than CN. CONCLUSION: The results of our study showed that CN significantly improves the survival of patients with metastatic CCRCC even in the targeted therapy era.

Assessment of survival of patients with metastatic clear cell renal cell carcinoma after radical cytoreductive nephrectomy versus no surgery: a SEER analysis

Purposes To examine the factors related to the choice of cytoreductive nephrectomy (CN) for patients with metastatic clear cell renal cell carcinoma (mCCRCC), and compare the population-based survival rates of patients treated with or without surgery in the modern targeted therapy era. Materials and Methods From 2006 to 2009, patients with mCCRCC were identified from SEER database. The factors that affected patients to be submitted to CN were examined and propensity scores for each patient were calculated. Then patients were matched based upon propensity scores. Univariable and multivariable cox regression models were used to compare survival rates of patients treated with or without surgery. Finally, sensitivity analysis for the cox model on a hazard ratio scale was performed. Results Age, race, tumor size, T stage and N stage were associated with nephrectomy univariablely. After the match based upon propensity scores, the 1-, 2-, and 3-year cancer-specific survival rate estimates were 45.1%, 27.9%, and 21.7% for the no-surgery group vs 70.6%, 52.2%, and 41.7% for the surgery group, respectively (hazard ratio 0.42, 95%CI: 0.35-0.52, log-rank P<0.001). In multivariable Cox proportional hazard regression model, race, T stage, N stage and median household income were significantly associated with survival. Sensitivity analysis on a hazard ratio scale indicated that the hazard ratio might be above 1.00 only when the unknown factor had an opposite effect on survival which was 3-fold than CN. Conclusion The results of our study showed that CN significantly improves the survival of patients with metastatic CCRCC even in the targeted therapy era. .

Pathological features of localized prostate cancer in China: a contemporary analysis of radical prostatectomy specimens.

There has been a rapid increase in the incidence of prostate cancer in China, especially in areas with boosted economic development. In this study, we analyzed the pathological features of a contemporary series of radical prostatectomy cases. A total of 230 consecutive, whole-mounted radical prostatectomy specimens collected from 2012 to 2014 were reviewed. The median age of the patients was 68 years, and 64.3% of patients presented with prostate specific antigen alone. Pathological examination indicated that a high proportion (77.4%) of patients had intermediate- or high-risk disease according to the Cancer of the Prostate Risk Assessment Post-Surgical score. After surgery, only 28 patients met the criteria for active surveillance (organ-confined Gleason ≥6 disease). The Prostate Cancer Research International Active Surveillance criteria achieved a sensitivity of 57.1% and a specificity of 98.0% for identifying candidates. The probability of Gleason score upgrading was 24.8% in the entire group and 59.0% in biopsy-confirmed Gleason ≥6 disease. The predominant tumor was located in the transition zone in 14.8% of cases, while only three patients (1.3%) had a predominant tumor located in the anterior region. Patients with transition zone-predominant tumor were likely to have been referred with urinary symptoms and high prostate specific antigen levels. The results of this study highlight the contemporary pathological features of localized prostate cancer in urban China. There was an increased trend towards asymptomatic cases, though most patients had intermediate- or high-risk disease and were suitable for definitive treatment. The low prevalence of dominant cancer in the anterior region may reflect race-based pathological differences.

Population-based assessment of the number of lymph nodes removed in the treatment of penile squamous cell carcinoma.

PURPOSE: To evaluate the number of lymph nodes (LNs) removed, as a performance measure of lymph node dissection (LND), in a population-based database. MATERIALS AND METHODS: Data from the Surveillance, Epidemiology, and End Results database (1988-2009) were used to identify 393 patients who underwent regional LND for penile cancer. The study cohort was divided into two groups: limited LND (<8 LNs removed) and extensive LND (≥8 LNs removed). Logistic regression analyses were performed to assess factors associated with extensive LND. Log-rank tests were used to evaluate the associations between LN evaluation and survival outcomes. RESULTS: The median number of removed LNs was 15, and 28% of patients underwent limited LND. The prevalence of extensive LND decreased gradually with increasing age: from 81% in men younger than 50 years to 65% in men aged 70 years or older. In multivariate analysis, only age retained an independent association with extensive LND (odds ratio = 0.98, p = 0.01). Log-rank test showed better cause-specific survival in patients receiving extensive LND (p = 0.006). The difference in survival was statistically significant in the subgroup of node-positive penile cancer patients (p = 0.01). CONCLUSIONS: An inadequate number of LN retrieval was observed in a considerable proportion of penile cancer patients, especially in the elderly population.