To assess the patterns and predictors of metastatic disease in renal cell carcinoma (RCC) at the time of diagnosis in a contemporary series.
The Surveillance, Epidemiology, and End Results database ...was queried for all patients with kidney RCC from 2010 to 2013 (N = 50,815). Distribution and predictors of distant metastases at diagnosis were assessed. Multivariate logistic regression hazard analyses were performed to determine covariates associated with the likelihood of having metastases at diagnosis, whereas competing risks regression analysis was used to assess predictors of cancer-specific mortality (CSM) in patients with metastatic disease.
Lung (7.73%) and bone (5.17%) metastases were the most common. The strongest predictors of metastatic disease were disease-specific factors, such as clinical T-stage (cT4 vs. cT1; odds ratio = 43.08; P<0.01) and higher Fuhrman grade (FG4 vs. FG1; odds ratio = 5.09; P<0.01). Papillary RCC and chromophobe RCC were associated with localized disease at the time of diagnosis. For CSM, the presence of brain and liver metastases were associated with worse CSM than lung or bone metastases. Although patient factors did not contribute to the presence of metastases at diagnosis, lower socioeconomic status and being widowed/divorced predicted worse CSM.
Understanding the distribution of distant metastases and associated CSM is important to counseling patients with newly diagnosed metastatic RCC. Although pathologic factors drive the presence of metastases at diagnosis, health care deficits in treatment remain.
•Goal: identify patterns and predictors of metastases at time of diagnosis in RCC.•Lung (7.73%) and bone (5.17%) mets more common than liver (2.6%) and brain (1.5%) mets.•Isolated bone metastases (11.1%) almost as common as isolated lung mets (16.8%).•Lower socioeconomic status and being widowed/divorced predicted higher CSM.•Health care deficit between diagnosis and treatment that still needs to be rectified.
Among patients with cancer, prior research suggests that patients with mental illness may have reduced survival. The objective was to assess the impact of psychiatric utilisation (PU) prior to cancer ...diagnosis on survival outcomes.
All residents of Ontario diagnosed with one of the top 10 malignancies (1997-2014) were included. The primary exposure was psychiatric utilisation gradient (PUG) score in 5 years prior to cancer: 0: none, 1: outpatient, 2: emergency department, 3: hospital admission. A multivariable, cause-specific hazard model was used to assess the effect of PUG score on cancer-specific mortality (CSM), and a Cox proportional hazard model for effect on all-cause mortality (ACM).
A toal of 676,125 patients were included: 359,465 (53.2%) with PUG 0, 304,559 (45.0%) PUG 1, 7901 (1.2%) PUG 2, and 4200 (0.6%) PUG 3. Increasing PUG score was independently associated with worse CSM, with an effect gradient across the intensity of pre-diagnosis PU (vs PUG 0): PUG 1 h 1.05 (95% CI 1.04-1.06), PUG 2 h 1.36 (95% CI 1.30-1.42), and PUG 3 h 1.73 (95% CI 1.63-1.84). Increasing PUG score was also associated with worse ACM.
Pre-cancer diagnosis PU is independently associated with worse CSM and ACM following diagnosis among patients with solid organ malignancies.
In the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents.
To ...indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC.
Medline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017. Abstracts of conferences of relevant medical societies were included, and the systematic search was supplemented by hand search. For the systematic review, we identified any parallel-group randomized controlled trials assessing first-line systemic therapy. For network meta-analysis, we limited these to a clinically-relevant network based on standard practice patterns. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and grade 3 and 4 adverse events (AEs) were secondary outcomes.
In total, 37 trials reporting on 13 128 patients were included in the systematic review. The network meta-analysis comprised 10 trials reporting on 4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood (SUCRA 91%) that cabozantinib was the preferred treatment. For OS (5 trials, 3379 patients), there was a 48% chance that nivolumab plus ipilimumab was the preferred option. There was a 67% likelihood that nivolumab plus ipilimumab was the best tolerated regime with respect to AEs.
Cabozantinib and nivolumab plus ipilimumab are likely to be the preferred first-line agents for treating mRCC; however, direct comparative studies are warranted. These findings may provide guidance to patients and clinicians when making treatment decisions and may help inform future direct comparative trials.
There are many treatment options for patients diagnosed with metastatic renal cell carcinoma. We indirectly compared the available options and found that cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as the first-line treatment in this situation.
There are many options for first-line therapy in metastatic renal cell carcinoma. However, there is a paucity of comparative data. Using a network meta-analysis approach, we found that cabozantanib and nivolumab plus ipilimumab are likely to be preferable agents in this space. However, these findings require validation in direct comparative studies.
To explore the current role of lymph node dissection (LND) in the management of nonmetastatic localized renal cell carcinoma (RCC).
There is currently no proven benefit of LND in the setting of RCC, ...and its role remains controversial because of conflicting evidence. Patients who may benefit from LND are those at greatest risk of nodal disease, but the tools used to predict nodal involvement are limited due to unpredictable retroperitoneal lymphatics. The indications, templates, and extent of LND are also not standardized, adding to the ambiguity of current guidelines surrounding its use.
A PubMed search of the literature from January 2017 to December 2022 was conducted using the search terms "renal cell carcinoma" or "renal cancer" in combination with "lymph node dissection" or "lymphadenectomy". Case studies and editorials were excluded, whereas studies investigating the therapeutic effect of LND were classified as either demonstrating a benefit or no benefit. References of the studies and review articles were also searched for notable studies and findings that were outside the five-year literature search. The studies in this review were restricted to the English language.
Only a number of studies in recent years have found an association between the extent of LND and increased survival. Most studies do not indicate an associated benefit, and some even suggest a negative effect on survival. Most of these studies are retrospective.
The therapeutic value of LND in RCC is still unclear, and although prospective data are needed, its declining rates and emerging new therapies make this unlikely. A better understanding of renal lymphatics and improved detection of nodal disease may help determine the role of LND in nonmetastatic localized RCC.
Multiple mechanisms of resistance contribute to the inevitable progression of hormone-sensitive prostate cancer to castration-resistant prostate cancer (CRPC). Currently approved therapies for CRPC ...include systemic chemotherapy (docetaxel and cabazitaxel) and agents targeting the resistance pathways leading to CRPC, including enzalutamide and abiraterone. While there is significant survival benefit, primary and secondary resistance to these therapies develops rapidly. Up to one-third of patients have primary resistance to enzalutamide and abiraterone; the remaining patients eventually progress on treatment. Understanding the mechanisms of resistance resulting in progression as well as identifying new targetable pathways remains the focus of current prostate cancer research. We review current knowledge of mechanisms of resistance to the currently approved treatments, development of adjunctive therapies, and identification of new pathways being targeted for therapeutic purposes.
Multiple risk factors have been associated with bladder cancer. This review focuses on pesticide exposure, as it is not currently known whether agricultural products have a direct or indirect effect ...on bladder cancer, despite recent reports demonstrating a strong correlation. While it is known that pesticide exposure is associated with an increased risk of bladder cancer in humans and dogs, the mechanism(s) by which specific pesticides cause bladder cancer initiation or progression is unknown. In this narrative review, we discuss what is currently known about pesticide exposure and the link to bladder cancer. This review highlights multiple pathways modulated by pesticide exposure with direct links to bladder cancer oncogenesis/metastasis (MMP-2, TGF-β, STAT3) and chemoresistance (drug efflux, DNA repair, and apoptosis resistance) and potential therapeutic tactics to counter these pesticide-induced affects.
ABSTRACT Purpose To identify incidence and predictors of stress urinary incontinence (SUI) following Holmium laser enucleation of the prostate (HoLEP). Materials and Methods We performed a ...retrospective review of 589 HoLEP patients from 2012-2018. Patients were assessed at pre-operative and post-operative visits. Univariate and multivariate regression analyses were performed to identify predictors of SUI. Results 52/589 patients (8.8%) developed transient SUI, while 9/589 (1.5%) developed long-term SUI. tSUI resolved for 46 patients (88.5%) within the first six weeks and in 6 patients (11.5%) between 6 weeks to 3 months. Long-term SUI patients required intervention, achieving continence at 16.4 months on average, 44 men (70.9%) with incontinence were catheter dependent preoperatively. Mean prostatic volume was 148.7mL in tSUI patients, 111.6mL in long-term SUI, and 87.9mL in others (p <0.0001). On univariate analysis, laser energy used (p <0.0001), laser “on” time (p=0.0204), resected prostate weight (p <0.0001), overall International Prostate Symptom Score (IPSS) (p=0.0005), and IPSS QOL (p=0.02) were associated with SUI. On multivariate analysis, resected prostate weight was predictive of any SUI and tSUI, with no risk factors identified for long-term SUI. Conclusion Post-HoLEP SUI occurs in ~10% of patients, with 1.5% continuing beyond six months. Most patients with tSUI recover within the first six weeks. Prostate size >100g and catheter dependency are associated with increased risk tSUI. Larger prostate volume is an independent predictor of any SUI, and tSUI.
Given the demographic trends toward a considerably longer life expectancy, the percentage of elderly patients with prostate cancer will increase further in the upcoming decades. Therefore, the ...question arises, should patients ≥75 years old be offered radical prostatectomy and under which circumstances? For treatment decision-making, life expectancy is more important than biological age. As a result, a patient′s health and mental status has to be determined and radical treatment should only be offered to those who are fit. As perioperative morbidity and mortality in these patients is increased relative to younger patients, patient selection according to comorbidities is a key issue that needs to be addressed. It is known from the literature that elderly men show notably worse tumor characteristics, leading to worse oncologic outcomes after treatment. Moreover, elderly patients also demonstrate worse postoperative recovery of continence and erectile function. As the absolute rates of both oncological and functional outcomes are still very reasonable in patients ≥75 years, a radical prostatectomy can be offered to highly selected and healthy elderly patients. Nevertheless, patients clearly need to be informed about the worse outcomes and higher perioperative risks compared to younger patients.
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.
Radiation for primary pelvic malignancies increases the risk of secondary malignancy development. However, outside of malignancies, with excellent cancer-specific survival, the impact of radiation on ...latency between primary and secondary malignancies is likely not enough to change practice patterns.
Radiation therapy has increasingly been used in the management of pelvic malignancies. However, the use of radiation continues to pose a risk of a secondary malignancy to its recipients. This study investigates the risk of secondary malignancy development following radiation for primary pelvic malignancies.
A retrospective cohort review of the Surveillance, Epidemiology, and End Results database from 1975 to 2016 was performed. Primary pelvic malignancies were subdivided based on the receipt of radiation, and secondary malignancies were stratified as pelvic or nonpelvic to investigate the local effect of radiation.
A total of 2102192 patients were analyzed (1189108 with prostate, 315026 with bladder, 88809 with cervical, 249535 with uterine, and 259714 with rectal/anal cancer). The incidence rate (defined as cases per 1000 person years) of any secondary malignancies (including but not limited to secondary pelvic malignancies) was higher in radiation patients than in nonradiation patients (incidence rate ratio IRR 1.04, confidence interval CI 1.03-1.05), with significantly greater rates noted in radiation patients with prostate (IRR 1.22, CI 1.21-1.24), uterine (IRR 1.34), and cervical (IRR 1.80, CI 1.72-1.88) cancer. While the overall incidence rate of any secondary pelvic malignancy was lower in radiation patients (IRR 0.79, CI 0.78-0.81), a greater incidence was still noted in the same cohorts including radiation patients with prostate (IRR 1.42, CI 1.39-1.45), uterine (IRR 1.15, CI 1.08-1.21), and cervical (IRR 1.72, CI 1.59-1.86) cancer.
Except for localized cervical cancer, when put in the context of median overall survival, the impact of radiation likely does not carry enough weight to change practice patterns. Radiation for pelvic malignancies increases the risk for several secondary malignancies, and more specifically, secondary pelvic malignancies, but with a relatively low absolute risk of secondary malignancies, the benefits of radiation warrant continued use for most pelvic malignancies. Practice changes should be considered for radiation utilization in malignancies with excellent cancer-specific survival such as cervical cancer.
The use of radiation for the management of pelvic malignancies induces a risk of secondary malignancies to its recipients. However, the absolute risk being low, the benefits of radiation warrant its continued use, and a change in practice patterns is unlikely.