Role of Metastasis-Directed Therapy in Genitourinary Cancers.

OPINION STATEMENT: The treatment of oligometastatic genitourinary cancers is a rapidly advancing field with ablative radiotherapy as one of the critical treatment components. The oligometastatic disease state, which can be defined as 1-5 metastatic sites with a controlled primary, represents a distinct clinical state where comprehensive ablative local therapies may provide improved outcomes. Enhanced imaging has increased the number of patients identified with oligometastatic disease. Evidence for improved outcomes with metastasis-directed therapy (MDT) in oligometastatic genitourinary cancers is increasing, and previously published outcome data continues to mature with an increasing body of prospective data to inform the role of MDT in histology-specific settings or in the context of systemic therapy. In select patients, MDT can offer benefits beyond improved local control and allow for time off of systemic therapy, prolonged time until next therapy, or even the hope of cure. However, treatment decisions for locally ablative therapy must be balanced with consideration towards safety. There are exciting advances in technologies to target and adapt treatment in real-time which have expanded options for safer delivery and dose escalation to metastatic targets near critical organs at risk. The role of systemic therapies in conjunction with MDT and incorporation of tumor genetic information to further refine prognostication and treatment decision-making in the oligometastatic setting is actively being investigated. These developments highlight the evolving field of treatment of oligometastatic disease. Future prospective studies combining MDT with enhanced imaging and integrating MDT with evolving systemic therapies will enable the optimal selection of patients most likely to benefit from this "all-or-none" approach and reveal settings in which a combination of therapies could result in synergistic outcomes.

Examining the trend of mortality of genitourinary system cancers in Babol, North Iran (2013-2021).

BACKGROUND: Cancers of the genitourinary system, particularly prostate, bladder, and kidney cancer, exhibit a high prevalence. Consequently, predicting the morbidity and mortality of genitourinary cancers holds great significance for future planning and implementation. This study aimed to examine the crude and age-standardized rates of mortality and the trend of genitourinary cancers over nine years in northern Iran. METHODS: This cross-sectional study used data on the number of deaths attributed to genitourinary cancers recorded in Babol City between 2013 and 2021 through the cause of death registration and classification system. Population estimates were derived from the latest census reports. Subsequently, crude and age-standardized rates, as well as trends for genitourinary cancers, were calculated. RESULTS: A total of 307 deaths occurred, with an average age of 75.6 ± 14.3 years due to genitourinary cancers. The crude and age-standardized rates of genitourinary cancers increased from 2.7 and 1.9 per hundred thousand people in 2013 to 7.7 and 5.9 per hundred thousand people in 2021, respectively. Over the study period, death rates significantly rose for men (P < 0.001) and remained constant for women (P = 0.444). Examination of genitourinary cancers revealed an upward trend for bladder (P = 0.012) and prostate (P = 0.012) cancers, while a stable trend was observed for kidney (P = 0.070) and testicular (P = 0.139) cancers. CONCLUSIONS: The age-standardized rate and trend of genitourinary cancers are rising. Consequently, this study emphasizes the importance of prevention through screening programs, raising awareness, and utilizing appropriate diagnostic methods.

Association between pelvic inflammatory disease and risk of ovarian, uterine, cervical, and vaginal cancers-a meta-analysis.

BACKGROUND AND AIM: The present meta-analysis aims to investigate a potential link between pelvic inflammatory disease (PID) and an increased risk of genitourinary cancers (ovarian, cervical, uterus, and vagina cancers). While previous research has hinted at a possible link, this meta-analysis seeks to delve deeper into the available evidence. Understanding this association is crucial for preventive strategies and improving clinical management practices. METHODOLOGY: A comprehensive literature search was conducted across various databases, covering studies published between 2016 and 2024. We included 13 observational studies meeting stringent criteria, followed by meticulous data extraction and quality assessment. Meta-analytical techniques were then employed to calculate pooled odds ratios (ORs), adjusted hazard ratios (HRs), and 95% confidence intervals (CIs), with heterogeneity assessed using the I2 statistic. RESULTS: Our analysis revealed significant findings, underscoring the association between PID and increased risks of genitourinary cancers. Specifically, individuals with a history of PID demonstrated notably higher odds of developing ovarian cancer (OR = 1.477, 95% CI 1.033-2.207), uterine cancer (OR = 1.263, 95% CI 0.827-2.143), cervical cancer (OR = 1.000, 95% CI 0.900-1.100), and vaginal cancer (OR = 2.500, 95% CI 1.400-4.000) compared to those without such a history. The overall heterogeneity across studies was high (I2 = 82.92%), suggesting varying trends across different populations and study designs. CONCLUSION: This meta-analysis provides updated evidence supporting a significant association between PID and an increased risk of cervical, ovarian, and uterine cancers. Early detection and management of PID are crucial in potentially mitigating the risk of these cancers.

MicroRNAs in Genitourinary Malignancies: An Exciting Frontier of Cancer Diagnostics and Therapeutics.

Genitourinary (GU) malignancies, including prostate, urothelial, kidney, testicular, penile, and adrenocortical cancers, comprise a significant burden of cancers worldwide. While many practice-changing advances have been made in the management of GU malignancies in the last decade, there is still significant room for improvement. MicroRNAs (miRNAs) are noncoding RNAs that regulate post-transcription gene expression and which have been implicated in multiple mechanisms of carcinogenesis. Therefore, they have the potential to revolutionize personalized cancer therapy, with several ongoing preclinical and clinical studies underway to investigate their efficacy. In this review, we describe the current landscape of miRNAs as diagnostics, therapeutics, and biomarkers of response for GU malignancies, reflecting a novel frontier in cancer treatment.

Microbiota and prostate cancer.

Prostate cancer remains the most frequently diagnosed non-skin malignancy in male patients, still representing one of the main causes of cancer-related death worldwide. Evidence is mounting that suggests the putative role of microbiota in the carcinogenesis as well as in modulating the efficacy and activity of anticancer treatments (e.g., chemotherapy, immune checkpoint inhibitors, targeted therapies) in a large number of hematological and solid tumors. However, few data are available regarding the interactions between prostate cancer and microbiome so far, in particular in terms of the impact of microbiota on disease development, pathogenesis, and response to medical treatments in this genitourinary malignancy. Herein, we provide an overview of current knowledge, novel insights and emerging therapeutic approaches related to gastrointestinal and genitourinary microbiome in prostate cancer patients, especially focusing on available evidence and published trials on this topic.

Experiences of sexual well-being interventions in males affected by genitourinary cancers and their partners: an integrative systematic review.

PURPOSE: Sexual well-being has been identified as an unmet supportive care need among many individuals with genitourinary (GU) cancers. Little is known about the experiences of using sexual well-being interventions among men and their partners. METHODS: This review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and followed a systematic review protocol. Data extraction and methodological quality appraisal were performed, and a narrative synthesis was conducted. RESULTS: A total of 21 publications (reporting on 18 studies) were included: six randomised control trials, seven cross-sectional studies, three qualitative studies, and five mixed methods studies. Sexual well-being interventions comprised medical/pharmacological and psychological support, including counselling and group discussion facilitation. The interventions were delivered using various modes: face-to-face, web-based/online, or telephone. Several themes emerged and included broadly: (1) communication with patient/partner and healthcare professionals, (2) educational and informational needs, and (3) timing and/or delivery of the interventions. CONCLUSION: Sexual well-being concerns for men and their partners were evident from diagnosis and into survivorship. Participants benefited from interventions but many articulated difficulties with initiating the topic due to embarrassment and limited access to interventions in cancer services. Noteworthy, all studies were only representative of men diagnosed with prostate cancer, underscoring a significant gap in other GU cancer patient groups where sexual dysfunction is a prominent consequence of treatment. IMPLICATIONS FOR CANCER SURVIVORS: This systematic review provides valuable new insights to inform future models of sexual well-being recovery interventions for patients and partners with prostate cancer, but further research is urgently needed in other GU cancer populations.

Discrepancies between genitourinary cancer patients' and clinicians' characterization of the Eastern Cooperative Oncology Group performance status.

BACKGROUND: Patient-reported outcomes have been used to assess treatment effectiveness and actively engage patients in their disease management. This study was designed to describe the patient-reported performance status (PS) and the provider-reported PS. METHODS: Patients with metastatic genitourinary cancers were recruited from a single cancer center before the initiation of a new line of treatment. PS (Eastern Cooperative Oncology Group [ECOG]), quality of life (Functional Assessment of Chronic Illness Therapy-General), and distress (Patient-Reported Outcomes Measurement Information System Anxiety and Depression) were self-reported by patients. Clinical data (eg, age, sex, diagnosis, and physician-reported ECOG PS) were extracted from medical records. Multivariate analysis was used to determine the association between PS, quality of life, and psychological symptoms. RESULTS: One hundred forty-five patients were enrolled (76.6% male, 70.3% White, 81.4% married, and 76.6% well educated). The median age was 67 years; 66.9% were diagnosed with renal cell carcinoma, 20.0% were diagnosed with urothelial carcinoma, and 13.1% were diagnosed with prostate cancer. Clinicians more frequently classified patients' ECOG PS as 0 in comparison with the patients themselves (92.4% vs 64.1%; P = .001). Higher clinician-reported ECOG PS was associated with poorer physical and functional well-being and higher rates of depression (P < .01), whereas higher patient-reported ECOG PS was associated with worse psychosocial outcomes (P < .01). CONCLUSIONS: Discrepancies were noted between the patient- and provider-reported ECOG PS, with clinicians overestimating the ECOG PS in comparison with the patients themselves. This study's findings suggest that patients incorporate their social and emotional well-being into their PS score in addition to their physical well-being. This information is not immediately accessible to most clinicians from just a standard patient interview and likely accounts for the overestimation of the patients' ECOG PS by the clinicians.

Is there an association between a history of military service and cancer diagnosis? Results from a US national-level study of self-reported outcomes.

PURPOSE: To examine cancer prevalence in men with and without military service history, using national-level self-reported outcomes. METHODS: A cross-sectional survey-based US study, including men aged 18 and above from the Health Information National Trends Survey database between 2011 and 2014. The primary endpoint was self-reported cancer prevalence. Multivariable logistic regression analyses assessed the association of various covariates with the prevalence of cancer. RESULTS: A total of 4,527 men were analyzed, with 1,352 (29.9%) reporting a history of military service. Compared to men with no military service history, men with a military service history were older (median of 65 [IQR 56, 74] vs. 53 [IQR 41, 62] years, p < 0.0001), more commonly Caucasian (71.4% vs. 61.4%, p < 0.0001), born in the US (95.6% vs. 79.5%, p < 0.0001), attained higher education level and annual household income (p < 0.0001), and consisted of more smokers(58.3% vs. 44.5%, p < 0.0001). The age-adjusted comparison demonstrated a higher cancer prevalence in men with military service history (20.5% vs. 7.6%, p < 0.0001). Specifically, genitourinary, dermatological, gastrointestinal, and hematological cancers were generally more prevalent. Adjusting for all available confounders, multivariable models showed that military service history was associated with 1.56 (95% CI 1.20-2.03), and 1.57 (95% CI 1.07-2.31) increased odds of having any cancer, and specifically genitourinary cancer, respectively. CONCLUSIONS: Further research is needed to ascertain whether the association between military service and increased cancer diagnosis results from better screening programs or increased exposure to risk factors during military service.

Prognosis of primary or metachronous prostate cancer in multiple primary genitourinary cancers; a single center experience with long-term results.

OBJECTIVE: This study aims to analyze the challenges, approaches and long-term results of primary or metachronous prostate cancer (PCa) in cases with multiple primary genitourinary cancers. METHODOLOGY: A total of 17 patients were included in the study. Patients with multiple primary genitourinary cancers were divided into two groups according to the diagnosis of primary or metachronous PCa as group 1 and group 2. RESULTS: The median age of patients was similar in both groups. The median smoking status (pack-years) was higher in group 2 than group 1. The median prostate-specific antigen (PSA) level was higher in group 1 than group 2. The median follow-up time from primary to the metachronous tumour was higher in group 1 than group 2. The rate of recurrence in PCa was higher in group 1 than group 2. No statistically significant difference was observed in terms of patients' age, smoking status, PSA levels at diagnosis of PCa and biochemical recurrence or metastasis between the two groups (p > 0.05). CONCLUSION: Primary PCa cases may progress more aggressively than metachronous PCa cases. Biochemical recurrence and metastasis may be less threatening in metachronous PCa cases than primary cases. Therefore, aggressive treatment can be avoided for metachronous PCa cases.

A global view of the challenges and limitations of precision medicine for genitourinary cancers.

Prostate and bladder cancers are the most common genitourinary cancers. In the past 2 decades, there has been increasing drug approval for these cancers, but there are patients who inherently do not respond or progress on such therapies highlighting the need for a better understanding of disease biology and mechanisms of resistance. Precision medicine has attempted to better select patients for specific therapies, although many advances have taken place in this field, access to targeted therapies and technology is distinct in different parts of the world. In this special Seminars issue, precision medicine and derived therapies were explored, as well as the impact on the management of prostate and bladder cancer, specially focusing on the challenges and limitations encountered by the international community when attempting to incorporate and implement the best clinical practice as recommended by worldwide accepted guidelines.

Hot topics in genitourinary cancers: A multidisciplinary discussion on state-of-the-art and latest developments among international experts and patient advocacy.

Genitourinary cancers present significant challenges to oncologists, necessitating innovative approaches for improved patient outcomes. The 'Controversies in Genitourinary Cancers' congress, held in January 2024, convened international experts to address the complexities of prostate, bladder, renal and rare genitourinary cancers. Sessions explored current trends, novel treatments, and unmet needs, emphasizing collaborative efforts to advance knowledge and patient care. Through multidisciplinary engagement and patient advocacy, the congress underscored the imperative of collective action in navigating the complexities of genitourinary cancers, ultimately aiming to transform clinical practice and improve patient outcomes.

Circulating Tumor DNA in Genitourinary Cancers: Detection, Prognostics, and Therapeutic Implications.

CtDNA is emerging as a non-invasive clinical detection method for several cancers, including genitourinary (GU) cancers such as prostate cancer, bladder cancer, and renal cell carcinoma (RCC). CtDNA assays have shown promise in early detection of GU cancers, providing prognostic information, assessing real-time treatment response, and detecting residual disease and relapse. The ease of obtaining a "liquid biopsy" from blood or urine in GU cancers enhances its potential to be used as a biomarker. Interrogating these "liquid biopsies" for ctDNA can then be used to detect common cancer mutations, novel genomic alterations, or epigenetic modifications. CtDNA has undergone investigation in numerous clinical trials, which could address clinical needs in GU cancers, for instance, earlier detection in RCC, therapeutic response prediction in castration-resistant prostate cancer, and monitoring for recurrence in bladder cancers. The utilization of liquid biopsy for ctDNA analysis provides a promising method of advancing precision medicine within the field of GU cancers.

Antibody-Drug Conjugates in the Treatment of Genitourinary Cancers: An Updated Review of Data.

The treatment landscape of genitourinary cancers has significantly evolved over the past few years. Renal cell carcinoma, bladder cancer, and prostate cancer are the most common genitourinary malignancies. Recent advancements have produced new targeted therapies, particularly antibody-drug conjugates (ADCs), due to a better understanding of the underlying oncogenic factors and molecular mechanisms involved. ADCs function as a 'drug delivery into the tumor' system. They are composed of an antigen-directed antibody linked to a cytotoxic drug that releases cytotoxic components after binding to the tumor cell's surface antigen. ADCs have been proven to be extremely promising in the treatment of several cancer types. For GU cancers, this novel treatment has only benefited patients with metastatic urothelial cancer (mUC). The rest of the GU cancer paradigm does not have any FDA-approved ADC treatment options available yet. In this study, we have thoroughly completed a narrative review of the current literature and summarized preclinical studies and clinical trials that evaluated the utility, activity, and toxicity of ADCs in GU cancers, the prospects of ADC development, and the ongoing clinical trials. Prospective clinical trials, retrospective studies, case reports, and scoping reviews were included.

Exosomes in Genitourinary Cancers: Emerging Mediators of Drug Resistance and Promising Biomarkers.

Drug resistance presents a major obstacle in the treatment of genitourinary cancers. Exosomes as the medium of intercellular communication serve important biological functions and play essential roles in pathological processes, including drug response. Through the transfer of bioactive cargoes, exosomes can modulate drug resistance via multiple mechanisms. This review attempts to elucidate the mechanisms of exosomal cargoes with reference to tumor drug resistance, their role in genitourinary cancers, and their potential clinical applications as candidate biomarkers in liquid biopsy.

Exploring the role of natural bioactive molecules in genitourinary cancers: how far has research progressed?

The primary approaches to treat cancerous diseases include drug treatment, surgical procedures, biotherapy, and radiation therapy. Chemotherapy has been the primary treatment for cancer for a long time, but its main drawback is that it kills cancerous cells along with healthy ones, leading to deadly adverse health effects. However, genitourinary cancer has become a concern in recent years as it is more common in middle-aged people. So, researchers are trying to find possible therapeutic options from natural small molecules due to the many drawbacks associated with chemotherapy and other radiation-based therapies. Plenty of research was conducted regarding genitourinary cancer to determine the promising role of natural small molecules. So, this review focused on natural small molecules along with their potential therapeutic targets in the case of genitourinary cancers such as prostate cancer, renal cancer, bladder cancer, testicular cancer, and so on. Also, this review states some ongoing or completed clinical evidence in this regard.

Review of Prospective Trials Assessing the Role of Stereotactic Body Radiation Therapy for Metastasis-directed Treatment in Oligometastatic Genitourinary Cancers.

CONTEXT: Emerging evidence supports the use of stereotactic body radiation therapy (SBRT) as metastatic-directed therapy (MDT) for oligometastatic genitourinary cancers; however, the prospective data to guide its application as an alternative standard of care remain limited. OBJECTIVE: To review prospective trials that assess the role of SBRT for patients with genitourinary cancers within a modern framework of oligometastatic disease (OMD) and to highlight clinical scenarios where SBRT may offer a benefit to patients with metastatic cancer. EVIDENCE ACQUISITION: We performed a critical review of PubMed and clinicaltrials.gov in April 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, combined with expert input to identify prospective studies investigating the role of SBRT for oligometastatic prostate, renal, or bladder cancer. EVIDENCE SYNTHESIS: The most commonly studied application of SBRT has been for metachronous oligorecurrent hormone-sensitive prostate cancer (HSPC). Further prospective study is needed to define the role of SBRT in delaying time to next therapy or inducing synergy with other systemic therapies. CONCLUSIONS: SBRT has been associated with high rates of local control and minimal risk of toxicity with multiple trials assessing an MDT-alone approach for oligorecurrent HSPC. From a tumor-agnostic perspective, the clinical benefit of SBRT for OMD has been associated with the ability to extend overall survival. As methods of cancer detection and treatment evolve, expansion of studies that prospectively evaluate SBRT MDT, stratifying by tumor histology and oligometastatic state, is needed to inform optimal patient selection and treatment strategy. PATIENT SUMMARY: We review outcomes from prospective trials assessing the role of stereotactic body radiation therapy (SBRT) for oligometastatic genitourinary cancers, which have predominantly investigated SBRT for oligorecurrent prostate cancer. Much work remains to define how SBRT alone compares with other standard of care treatments for prostate cancer or the role of SBRT in tumor control or delaying time to next therapy in oligometastatic renal and bladder cancer.

Analysis of Health-Related Quality of Life Reporting in Phase III RCTs of Advanced Genitourinary Tumors.

BACKGROUND: As recommended in the European Society for Medical Oncology (ESMO) guidelines, assessment of health-related quality of life (HRQoL) should be a relevant endpoint in randomized controlled trials (RCTs) testing new anticancer therapies. However, previous publications by our group and others revealed a frequent underestimation and underreporting of HRQoL results in publication of RCTs in oncology. Herein, we systematically reviewed HRQoL reporting in RCTs testing new treatments in advanced prostate, kidney and urothelial cancers and published between 2010 and 2022. METHODS: We searched PubMed RCTs testing novel therapies in genitourinary (GU) cancers and published in fifteen selected journals (Annals of Oncology, BMC Cancer, British Journal of Cancer, Cancer Discovery, Clinical Cancer Research, Clinical Genitourinary cancer, European Journal of Cancer, European Urology, European Urology Oncology, JAMA, JAMA Oncology, Journal of clinical Oncology, Lancet, Lancet Oncology and The New England Journal of Medicine). We excluded trials investigating exclusively best supportive care or behavioral intervention, as well as subgroup or post hoc analyses of previously published trials. For each RCT, we investigated whether HRQoL assessment was performed by protocol and if results were reported in the primary manuscript or in a secondary publication. RESULTS: We found 85 eligible trials published between 2010 and 2022. Only 1/85 RCTs (1.2%) included HRQoL among primary endpoints. Of note, 25/85 (29.4%) RCTs did not include HRQoL among study endpoints. HRQoL results were non-disclosed in 56/85 (65.9%) primary publications. Only 18/85 (21.2%) publications fulfilled at least one item of the CONSORT-PRO checklist. Furthermore, 14/46 (30.4%) RCTs in prostate cancer, 12/25 (48%) in kidney cancer and 3/14 (21.4%) in urothelial cancer reported HRQoL data in primary publications. Next, HRQoL data were disclosed in primary manuscripts of 12/32 (37.5%), 5/13 (38.5%), 5/16 (31.3%) and 5/15 (33.3%) trials evaluating target therapies, chemotherapy, immunotherapy and new hormonal agents, respectively. Next, we found that HRQoL data were reported in 16/42 (38%) and in 13/43 (30.2%) positive and negative trials, respectively. Finally, the rate of RCTs reporting HRQoL results in primary or secondary publications was 55.3% (n = 47/85). CONCLUSIONS: Our analysis revealed a relevant underreporting of HRQoL in RCTs in advanced GU cancers. These results highlight the need to dedicate more attention to HRQoL in RCTs to fully assess the value of new anticancer treatments.

The impact of coronavirus disease 2019 on genitourinary and prostate cancer care and clinical trials: A qualitative exploration of the Australian and New Zealand experience.

PURPOSE: This qualitative study aimed to understand the impact of the coronavirus disease 2019 pandemic from March to November 2020 on healthcare delivery and clinical trials for genitourinary (GU) cancers in Australia. METHODS: Annually a pre-conference workshop is hosted by the Australian New Zealand Urogenital and Prostate Cancer Trials Group for supportive care health professionals. In November 2020, those that selected to attend were invited to participate in a focus group. Workshop and focus group discussions were recorded and transcripts were analyzed thematically. RESULTS: Seventy-two individuals involved in GU cancer care and clinical trials took part. Participants described negative changes to GU cancer care and clinical trials from the pandemic due to reduced clinical services and increased wait times. Trial recruitment was paused temporarily during lockdowns, and standard treatment protocols were used to limit hospital visits. Trial process changes included electronic capture of informed consent, home delivery of oral medications, and delegations of assessments. These changes increased administrative activity for clinical trial teams and Human Research Ethics Committees. A transition to telehealth enabled continuity of service delivery and trials but reduced the opportunity for face-to-face patient consultations with increasing concern about the failure to detect supportive care needs. CONCLUSION: The pandemic has prompted a critical review of service delivery and clinical trials for people with GU cancers.

Trends and risk factors of global incidence, mortality, and disability of genitourinary cancers from 1990 to 2019: Systematic analysis for the Global Burden of Disease Study 2019.

Background: The incidence of kidney, bladder, and prostate cancer ranked ninth, sixth, and third in male cancers respectively, meanwhile, the incidence of testicular cancer also increased gradually in the past 30 years. Objective: To study and present estimates of the incidence, mortality, and disability of kidney, bladder, prostate, and testicular cancer by location and age from 1990 to 2019 and reveal the mortality risk factors of them. Materials: The Global Burden of Diseases Study 2019 was used to obtain data for this research. The prediction of cancer mortality and incidence was based on mortality-to-incidence ratios (MIRs). The MIR data was processed by logistic regression and adjusted by Gaussian process regression. The association between the socio-demographic index and the incidence or disease burden was determined by Spearman's rank order correlation. Results: Globally in 2019, there were 371,700 kidney cancer cases with an age-standardized incidence rate (ASIR) of 4.6 per 100,000, 524,300 bladder cancer cases, with an ASIR of 6.5 per 100,000, 1,410,500 prostate cancer cases with an ASIR of 4.6 per 100,000 and 109,300 testicular cancer incident cases with an ASIR of 1.4 per 100,000, the ASIR of these four cancers increased by 29.1, 4, 22, and 45.5% respectively. The incidence rate of the four cancers and the burden of kidney cancer were positively correlated with the socio-demographic index (SDI), regions with a higher SDI faced more of a burden attributable to these four cancers. High body-mass index has surpassed smoking to be the leading risk factor in the past thirty years for kidney cancer mortality. Smoking remained the leading risk factor for cancer-related mortality for bladder cancer and prostate cancer and the only risk factor for prostate cancer. However, the contribution of high fasting plasma glucose to bladder cancer mortality has been increasing. Conclusion: The incidence of bladder, kidney, prostate, and testicular cancer is ever-increasing. High-income regions face a greater burden attributable to the four cancers. In addition to smoking, metabolic risk factors may need more attention.

Increasing cure rates of solid tumors by immune checkpoint inhibitors.

Immunotherapy has become the central pillar of cancer therapy. Immune checkpoint inhibitors (ICIs), a major category of tumor immunotherapy, reactivate preexisting anticancer immunity. Initially, ICIs were approved only for advanced and metastatic cancers in the salvage setting after or concurrent with chemotherapy at a response rate of around 20-30% with a few exceptions. With significant progress over the decade, advances in immunotherapy have led to numerous clinical trials investigating ICIs as neoadjuvant and/or adjuvant therapies for resectable solid tumors. The promising results of these trials have led to the United States Food and Drug Administration (FDA) approvals of ICIs as neoadjuvant or adjuvant therapies for non-small cell lung cancer, melanoma, triple-negative breast cancer, and bladder cancer, and the list continues to grow. This therapy represents a paradigm shift in cancer treatment, as many early-stage cancer patients could be cured with the introduction of immunotherapy in the early stages of cancer. Therefore, this topic became one of the main themes at the 2021 China Cancer Immunotherapy Workshop co-organized by the Chinese American Hematologist and Oncologist Network, the China National Medical Products Administration and the Tsinghua University School of Medicine. This review article summarizes the current landscape of ICI-based immunotherapy, emphasizing the new clinical developments of ICIs as curative neoadjuvant and adjuvant therapies for early-stage disease.