The incidence of urothelial carcinoma of the urinary bladder (bladder cancer) remains high. While other solid organ malignancies have seen significant improvement in morbidity and mortality, there has been little change in bladder cancer mortality in the past few decades. The mortality is mainly driven by muscle invasive bladder cancer, but the cancer burden remains high even in nonmuscle invasive bladder cancer due to high recurrence rates and risk of progression. While apoptosis deregulation has long been an established pathway for cancer progression, nonapoptotic pathways have gained prominence of late. Recent research in the role of autophagy in other malignancies, including its role in treatment resistance, has led to greater interest in the role of autophagy in bladder cancer. Herein, we summarize the literature regarding the role of autophagy in bladder cancer progression and treatment resistance. We address it by systematically reviewing treatment modalities for nonmuscle invasive and muscle invasive bladder cancer.

Purpose

We evaluated the use and efficacy of intraoperative urinary diversion with ureteral stent or nephrostomy tube during pyeloplasty in children.

Materials and methods

The Faculty Practice Solutions Center® national billing database was queried to identify all pediatric pyeloplasties performed from 2009 to 2012. Patient variables, surgical approach, use of intraoperative stent/nephrostomy tube and return for postoperative stent/nephrostomy tube or second pyeloplasty were obtained.

Results

A total of 2,435 children underwent open (1,792) or laparoscopic/robotic (643) pyeloplasty, with intraoperative urinary diversion rates of 45% and 83%, respectively. Comparing patients with and without an intraoperative stent/nephrostomy tube, 5.6% and 7.4%, respectively, returned to the hospital for urinary diversion. Multivariable analysis revealed no association with surgical approach, but higher surgeon volume (p <0.01) and use of an intraoperative stent/nephrostomy tube (p <0.01) were associated with decreased odds of requiring postoperative urinary diversion. Second pyeloplasty rate was 3.8% and was not associated with surgical approach or use of intraoperative stent/nephrostomy tube.

Conclusions

Intraoperative stent/nephrostomy tube use and increased surgeon volume were each independently associated with a significant but small decrease in risk of postoperative stent/nephrostomy tube placement. Use of an intraoperative stent/nephrostomy tube was not associated with rate of second (redo ipsilateral or contralateral metachronous) pyeloplasty.

Purpose

To explore the current role of lymph node dissection (LND) in the management of nonmetastatic localized renal cell carcinoma (RCC).

Background

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.

Evidence acquisition

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.

Results

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.

Conclusion

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.

Objective

To utilize a population-based approach to address the role of adjuvant TT in the management of RCC.

Methods

Patients with RCC (2006-2013) in the SEER database were stratified by metastatic disease at the time of diagnosis (cM0/cM1). cM0 patients following surgical excision were stratified into low and high-risk (ASSURE and S-TRAC criteria). Multivariable analyses performed to identify predictors of TT receipt; Fine and Gray competing risks analyses used to identify predictors of cancer-specific mortality (CSM). Subset analyses included patients with clear cell histology and high-risk cM0. Survival analyses were used to evaluate overall survival (OS) and cancer-specific survival (CSS) for all cohorts, stratified on TT receipt.

Results

79,926 patients included (71,682 cM0, 8,244 cM1); median follow-up for the entire cohort was 40.1 months. Of 31,453 patients with histologic grade data, 18,328 and 13,125 were low- and high-risk cM0, respectively. TT utilization in cM1 patients peaked at 50.6% and was associated with reduced CSM (HR 0.73, p<0.01). In contrast, TT utilization (presumed salvage therapy) never exceeded 2.2% in the entire cM0 cohort and 3.5% in the high-risk cM0 cohort. On competing risks analysis, TT receipt was associated with increased CSM in all cohorts.

Conclusion

When compared to the cM1 patients, TT receipt in cM0 patients does not provide any cancer-specific survival benefit, even in the small percentage of patients that eventually progress to metastatic disease. Competing risks mortality further limit any potential benefit in this population. Based on current evidence, adjuvant TT cannot be recommended for RCC patients.

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.

Despite advances in prostate cancer diagnosis and management, morbidity from prostate cancer remains high. Approximately 20% of men present with advanced or metastatic disease, while 29,000 men continue to die of prostate cancer each year. Androgen deprivation therapy (ADT) has been the standard of care for initial management of advanced or metastatic prostate cancer since Huggins and Hodges first introduced the concept of androgen-dependence in 1972, but progression to castration-resistant prostate cancer (CRPC) occurs within 2-3 years of initiation of ADT. CRPC, previously defined as hormone-refractory prostate cancer, is now understood to still be androgen dependent. Multiple mechanisms of resistance help contribute to the progression to castration resistant disease, and the androgen receptor (AR) remains an important driver in this progression. These mechanisms include AR amplification and hypersensitivity, AR mutations leading to promiscuity, mutations in coactivators/corepressors, androgen-independent AR activation, and intratumoral and alternative androgen production. More recently, identification of AR variants (ARVs) has been established as another mechanism of progression to CRPC. Docetaxel chemotherapy has historically been the first-line treatment for CRPC, but in recent years, newer agents have been introduced that target some of these mechanisms of resistance, thereby providing additional survival benefit. These include AR signaling inhibitors such as enzalutamide (Xtandi, ENZA, MDV-3100) and CYP17A1 inhibitors such as abiraterone acetate (Zytiga). Ultimately, these agents will also fail to suppress CRPC. While some of the mechanisms by which these agents fail are unique, many share similarities to the mechanisms contributing to CRPC progression. Understanding these mechanisms of resistance to ADT and currently approved CRPC treatments will help guide future research into targeted therapies.

Background

Current data on the association between tumor size, subtype, and metastases, and thresholds for intervention, for renal cell carcinoma (RCC), are largely based on single-center nephrectomy registries that may under-represent those presenting with metastatic disease.

Objective

We sought to assess tumor size and histologic subtype in relation to metastatic status at presentation for patients with RCC.

Design setting and participants

Using Surveillance, Epidemiology and End Results cancer registry data, we identified patients with a diagnosis of RCC made between 2004 and 2019, and a known size of primary tumor. We used nodal and metastatic TNM staging to assess metastatic disease at presentation.

Outcome measurements and statistical analysis

We report the proportion of metastatic disease across varying tumor sizes for clear cell (ccRCC), papillary (pRCC), and chromophobe (chRCC) RCC. We also examine sarcomatoid RCC and RCC with sarcomatoid features (sarcRCC). Logistic regression models were used to model the likelihood of metastatic disease for each histologic subtype.

Results and limitations

Of 181 096 RCC patients included, 23 829 had metastatic disease. For any RCC, metastatic rates of 3.6%, 13.1%, 30.3%, and 45.1% were observed for tumors ≤4, 4-≤7, 7-≤10, and >10 cm, respectively. Metastatic rates of chRCC were low at even large sizes, 11.0% at >10 cm. In contrast, sarcRCC had high metastatic rates at all sizes, 27.1% at ≤4 cm. Metastatic rates for ccRCC and pRCC increased steadily above 3 cm. For any RCC and each evaluated subtype, tumor size was found to be associated with metastatic disease on logistic regression (p < 0.001).

Conclusions

The likelihood of a renal mass being metastatic varies greatly with both its subtype and size. We report higher likelihoods of metastatic disease across tumor sizes compared with what has been reported previously. These results may help clinicians pick appropriate thresholds for intervention and candidates for active surveillance.

Patient summary

We find that the metastatic probability of renal cell carcinoma varies greatly with subtype and increases with tumor size.

Purpose

Prostate cancer (PCa) screening, which relies on prostate-specific antigen (PSA) testing, is a contentious topic that received negative attention due to the low sensitivity and specificity of PSA to detect clinically significant PCa. In this context, due to the higher sensitivity and specificity of magnetic resonance imaging (MRI), several trials investigate the feasibility of "MRI-only" screening approaches, and question if PSA testing may be replaced within prostate cancer screening programs.

Methods

This narrative review discusses the current literature and the outlook on the potential of MRI-based PCa screening.

Results

Several prospective randomized population-based trials are ongoing. Preliminary study results appear to favor the "MRI-only" approach. However, MRI-based PCa screening programs face a variety of obstacles that have yet to be fully addressed. These include the increased cost of MRI, lack of broad availability, differences in MRI acquisition and interpretation protocols, and lack of long-term impact on cancer-specific mortality. Partly, these issues are being addressed by shorter and simpler MRI approaches (5-20 min bi-parametric MRI), novel quality indicators (PI-QUAL) and the implementation of radiomics (deep learning, machine learning).

Conclusion

Although promising preliminary results were reported, MRI-based PCa screening still lack long-term data on crucial endpoints such as the impact of MRI screening on mortality. Furthermore, the issues of availability, cost-effectiveness, and differences in MRI acquisition and interpretation still need to be addressed.

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.

There remains debate surrounding partial (PN) versus radical nephrectomy (RN) for T1b-T2 renal cell carcinoma (RCC). PN offers nephron-sparing benefits but involves increased perioperative complications. RN putatively maximizes oncologic benefit with complex tumors. We analyzed newly available nephrectomy-specific NSQIP data to elucidate predictors of perioperative outcomes in localized T1b-T2 RCC. We identified 2094 patients undergoing nephrectomy between 2019-2020. Captured variables include surgical procedure and approach, staging, comorbidities, prophylaxis, peri-operative complications, reoperations, and readmissions. 816 patients received PN while 1278 received RN. Reoperation rates were comparable; however, PN patients more commonly experienced 30-day readmissions (7.0% vs. 4.7%, p = 0.026), bleeds (9.19% vs. 5.56%, p = 0.001), renal failure requiring dialysis (1.23% vs. 0.31%, p = 0.013) and urine leak or fistulae (1.10% vs. 0.31%, p = 0.025). Infectious, pulmonary, cardiac, and venothromboembolic event rates were comparable. Robotic surgery reduced occurrence of various complications, readmissions, and reoperations. PN remained predictive of all four complications upon multivariable adjustment. Several comorbidities were predictive of complications including bleeds and readmissions. This population-based cohort explicates perioperative outcomes following nephrectomy for pT1b-T2 RCC. Significant associations between PN, patient-specific factors, and complications were identified. Risk stratification may inform management to improve post-operative quality of life (QOL) and RCC outcomes.