Differences in Patient-Reported Outcomes That Are Most Frequently Detected in Randomized Controlled Trials in Patients With Solid Tumors:A Pooled Analysis of 229 Trials

ObjectivesPatient-reported outcome (PRO) measurements used in cancer research can assess a number of health domains. Our primary objective was to investigate which broad types of PRO domains (namely, functional health, symptoms, and global quality of life [QoL]) most frequently yielded significant differences between treatments in randomized controlled trials (RCTs).MethodsA total of 229 RCTs published between January 2004 and February 2019, conducted on patients diagnosed with the most common solid malignancies and assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, were considered. Studies were identified systematically using literature searches in key electronic databases. Unlike other PRO measurements typically used in RCTs, the scoring algorithm of the multidimensional EORTC QLQ-C30 allowed us to clearly distinguish the 3 broad types of PRO domains.ResultsIn total, 134 RCTs (58.5%) reported statistically significant differences between treatment arms for at least 1 of the QLQ-C30 domains. Most frequently, differences were reported for 2 or all 3 broad types of PRO domains (78 of 134 trials; 58.2%). In particular, 35 trials (26.1%) found significant differences for symptoms, functional health, and global QoL, 24 trials (17.9%) for symptoms and functional health, 11 trials (8.2%) for functional health and global QoL, and 8 trials (6.0%) for symptoms and global QoL. The likelihood of finding a statistically significant difference between treatment arms was not associated with key study characteristics, such as study design (ie, open-label vs blinded trials) and industry support.ConclusionsOur findings emphasize the importance of a multidimensional PRO assessment to most comprehensively capture the overall burden of therapy from the patients’ standpoint

Non-muscle invasive bladder cancer risk stratification

Introduction: Non-muscle invasive bladder cancer (NMIBC) comprises about 70% of all newly diagnosed bladder cancer, and includes tumors with stage Ta, T1 and carcinoma in situ (CIS.) Since, NMIBC patients with progression to muscle-invasive disease tend to have worse prognosis than with patients with primary muscle-invasive disease, there is a need to significantly improve risk stratification and earlier definitive treatment for high-risk NMIBC. Materials and Methods: A detailed Medline search was performed to identify all publications on the topic of prognostic factors and risk predictions for superficial bladder cancer/NMIBC. The manuscripts were reviewed to identify variables that could predict recurrence and progression. Results: The most important prognostic factor for progression is grade of tumor. T category, tumor size, number of tumors, concurrent CIS, intravesical therapy, response to bacillus Calmette–Guerin at 3- or 6-month follow-up, prior recurrence rate, age, gender, lymphovascular invasion and depth of lamina propria invasion are other important clinical and pathological parameters to predict recurrence and progression in patients with NMIBC. The European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Club UrológicoEspañol de Tratamiento Oncológico (CUETO) risk tables are the two best-established predictive models for recurrence and progression risk calculation, although they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Molecular biomarkers such as Ki-67, FGFR3 and p53 appear to be promising in predicting recurrence and progression but need further validation prior to using them in clinical practice. Conclusion: EORTC and CUETO risk tables are the two best-established models to predict recurrence and progression in patients with NMIBC though they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Future research should focus on enhancing the predictive accuracy of risk assessment tools by incorporating additional prognostic factors such as depth of lamina propria invasion and molecular biomarkers after rigorous validation in multi-institutional cohorts

Nuclear morphometry, nucleomics and prostate cancer progression

Prostate cancer (PCa) results from a multistep process. This process includes initiation, which occurs through various aging events and multiple insults (such as chronic infection, inflammation and genetic instability through reactive oxygen species causing DNA double-strand breaks), followed by a multistep process of progression. These steps include several genetic and epigenetic alterations, as well as alterations to the chromatin structure, which occur in response to the carcinogenic stress-related events that sustain proliferative signaling. Events such as evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis are readily observed. In addition, in conjunction with these critical drivers of carcinogenesis, other factors related to the etiopathogenesis of PCa, involving energy metabolism and evasion of the immune surveillance system, appear to be involved. In addition, when cancer spread and metastasis occur, the ‘tumor microenvironment' in the bone of PCa patients may provide a way to sustain dormancy or senescence and eventually establish a ‘seed and soil' site where PCa proliferation and growth may occur over time. When PCa is initiated and progression ensues, significant alterations in nuclear size, shape and heterochromatin (DNA transcription) organization are found, and key nuclear transcriptional and structural proteins, as well as multiple nuclear bodies can lead to precancerous and malignant changes. These series of cellular and tissue-related malignancy-associated events can be quantified to assess disease progression and management