Prostate cancer radiogenomics—from imaging to molecular characterization

Radiomics and genomics represent two of the most promising fields of cancer research, designed to improve the risk stratification and disease management of patients with prostate cancer (PCa). Radiomics involves a conversion of imaging derivate quantitative features using manual or automated algorithms, enhancing existing data through mathematical analysis. This could increase the clinical value in PCa management. To extract features from imaging methods such as magnetic resonance imaging (MRI), the empiric nature of the analysis using machine learning and artificial intelligence could help make the best clinical decisions. Genomics information can be explained or decoded by radiomics. The development of methodologies can create more-efficient predictive models and can better characterize the molecular features of PCa. Additionally, the identification of new imaging biomarkers can overcome the known heterogeneity of PCa, by non-invasive radio-logical assessment of the whole specific organ. In the future, the validation of recent findings, in large, randomized cohorts of PCa patients, can establish the role of radiogenomics. Briefly, we aimed to review the current literature of highly quantitative and qualitative results from well-de-signed studies for the diagnoses, treatment, and follow-up of prostate cancer, based on radiomics, genomics and radiogenomics research

Impact of Age on Outcomes of Patients With Pure Carcinoma In Situ of the Bladder: Multi-Institutional Cohort Analysis

Introduction: The aim of this multicenter study was to investigate the role of age (cut-off 70 years) at diagnosis in predicting oncologic behavior of pure carcinoma in situ of the bladder. Material and Methods: Inclusion criteria were: patients with pure CIS confirmed and that followed intravesical BCG treatment. Pure CIS was defined at any CIS not associated with another urothelial cancer. Exclusion criteria were: any CIS associated with invasive urothelial carcinoma. A total of 172 with pure CIS treated between January 1, 2002 and December 31, 2012 at 8 academic institutions met the inclusion criteria. The maintenance schedule was generally according to the EAU guidelines at the time Results: A total of 99 (57.6%) patients had an age >70 years prior to TURBT. There was no difference between clinico-pathologic features among groups (group 1, age ≤ 70 years and group 2, age > 70 years), except that patients aged ≤ 70 years presented a larger size of CIS (35.6% vs. 21.2%), P =.02. In multivariable Cox regression analyses, the same clinico-pathologic factors (age, multifocality, and recurrent tumor state) were independently associated with worse RFS. Harrell's C-index was 65.75.In multivariable Cox regression analyses in addition to age (P =.006) and multifocality (P <.001) also BMI (P =.04) was independently associated with worse PFS. Harrell's C-index was 74.71 Conclusion: Advanced age at diagnosis appears to be associated with an increased risk of recurrence and progression of pure carcinoma in situ of the bladder. Elderly patients might fail to respond to BCG therapy

Impact of Age on Outcomes of Patients With Pure Carcinoma In Situ of the Bladder: Multi-Institutional Cohort Analysis

Introduction: The aim of this multicenter study was to investigate the role of age (cut-off 70 years) at diagnosis in predicting oncologic behavior of pure carcinoma in situ of the bladder. Material and methods: Inclusion criteria were: patients with pure CIS confirmed and that followed intravesical BCG treatment. Pure CIS was defined at any CIS not associated with another urothelial cancer. Exclusion criteria were: any CIS associated with invasive urothelial carcinoma. A total of 172 with pure CIS treated between January 1, 2002 and December 31, 2012 at 8 academic institutions met the inclusion criteria. The maintenance schedule was generally according to the EAU guidelines at the time RESULTS: A total of 99 (57.6%) patients had an age &gt;70 years prior to TURBT. There was no difference between clinico-pathologic features among groups (group 1, age ≤ 70 years and group 2, age &gt; 70 years), except that patients aged ≤ 70 years presented a larger size of CIS (35.6% vs. 21.2%), P = .02. In multivariable Cox regression analyses, the same clinico-pathologic factors (age, multifocality, and recurrent tumor state) were independently associated with worse RFS. Harrell's C-index was 65.75.In multivariable Cox regression analyses in addition to age (P = .006) and multifocality (P &lt; .001) also BMI (P = .04) was independently associated with worse PFS. Harrell's C-index was 74.71 CONCLUSION: Advanced age at diagnosis appears to be associated with an increased risk of recurrence and progression of pure carcinoma in situ of the bladder. Elderly patients might fail to respond to BCG therapy

Modified Glasgow Prognostic Score as a Predictor of Recurrence in Patients with High Grade Non-Muscle Invasive Bladder Cancer Undergoing Intravesical Bacillus Calmette–Guerin Immunotherapy

Background: A systemic inflammatory marker, the modified Glasgow prognostic score (mGPS), could predict outcomes in non-muscle-invasive bladder cancer (NIMBC). We aimed to investigate the predictive power of mGPS in oncological outcomes in HG/G3 T1 NMIBC patients undergoing Bacillus Calmette–Guérin (BCG) therapy. Methods: We retrospectively reviewed patient’s medical data from multicenter institutions. A total of 1382 patients with HG/G3 T1 NMIBC have been administered adjuvant intravesical BCG therapy, every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months. The analysis of mGPS for recurrence and progression was performed using multivariable and univariable Cox regression models. Results: During follow-up, 659 patients (47.68%) suffered recurrence, 441 (31.91%) suffered progression, 156 (11.28%) died of all causes, and 67 (4.84%) died of bladder cancer. At multivariable analysis, neutrophil to lymphocyte ratio [hazard ratio (HR): 7.471; p = 0.0001] and erythrocyte sedimentation rate (ESR) (HR: 0.706; p = 0.006 were significantly associated with recurrence. mGPS has no statistical significance for progression (p = 0.076). Kaplan–Meier survival analysis showed a significant difference in survival among patients from different mGPS subgroups. Five-year OS was 93% (CI 95% 92–94), in patients with mGPS 0, 82.2% (CI 95% 78.9–85.5) in patients with mGPS 1 and 78.1% (CI 95% 60.4–70) in mGPS 2 patients. Five-year CSS was 98% (CI 95% 97–99) in patients with mGPS 0, 90% (CI 95% 87–94) in patients with mGPS 1, and 100% in mGPS 2 patients. Limitations are applicable to a retrospective study. Conclusions: mGPS may have the potential to predict recurrence in HG/G3 T1 NMIBC patients, but more prospective, with large cohorts, studies are needed to study the influence of systemic inflammatory markers in prediction of outcomes in NMIBC for a definitive conclusion

Predictive clinico-pathological factors to identify BCG, unresponsive patients, after re-resection for T1 high grade non-muscle invasive bladder cancer

Introduction: Seventy-five percent of bladder cancers are non-muscle invasive. The treatment strategy includes the transurethral resection of bladder tumor (TURB) followed by intravesical immunotherapy with the bacillus of Calmette-Guerin (BCG) or chemotherapy, depending on the grade of bladder tumor. Despite a proper BCG intravesical instillations schedule, up to 40% of patients present a failure within 2 years. The aim of this retrospective study was to investigate the predictive factors in the response to BCG in patients with a high-grade non-muscle invasive bladder cancer diagnosis. Materials and methods: Patients with non-muscle invasive bladder cancer from 13 hospitals and academic institutions were identified and treated, from January 1, 2002, until December 31, 2012, with TURB and a subsequent re-TURB for restaging before receiving BCG. Follow-up was performed with urine cytology and cystoscopy every 3 months for 1 year and, successively every 6 months. Univariate and multivariate Cox regression models addressed the response to BCG therapy. Kaplan-Meier overall survival (OS) and cancer-specific survival (CSS) estimates were determined for BCG responsive vs. BCG unresponsive patients. Results: A total of 1,228 patients with non-muscle invasive bladder cancer were enrolled. Of 257 (20.9%) patients were BCG unresponsive. Independent predictive factors for response to BCG were: multifocality (HR: 1.4; 95% CI 1.05-1.86; P = 0.019), lymphovascular invasion (HR: 1.75; 95% CI 1.22-2.49; P = 0.002) and high-grade on re-TURB (HR: 1.39; 95% CI 1.02-1.91; P = 0.037). Overall survival was significantly reduced in BCG-unresponsive patients compared to BCG-responsive patients at 5 years (82.9% vs. 92.4%, P &lt; 0.0001) and at 10 years (44.2% vs. 74.4%, P &lt; 0.0001). Similarly, cancer-specific survival was reduced in BCG-unresponsive patients at 5 years (90.6% vs. 97.3%, P &lt; 0.0001) and at 10 years (72.3% vs. 87.2%, P &lt; 0.0001). Conclusion: Multifocality, lymphovascular invasion, and high-grade on re-TURB were independent predictors for response to BCG treatment. BCG-unresponsive patients reported worse oncological outcomes