Contemporary update of SPECT tracers and novelties in radioguided surgery: a perspective based on urology

Recent technical advances and implementation of novel radiotracers have further increased the potential of radioguided surgery for a broad variety of malignancies. Indeed, the possibilities for future applications of novel radiotracers in diverse degrees neologiesl strategies has become more promising than ever. This literature review aims to provide a contemporary update on a selected group of radiotracers and evaluates the usability of radioguided surgery and sentinel node procedures, focusing on most promising advances. For example, the impact of targeted radiotracers on prostate specific membrane antigen (PSMA), CD206 receptor-targeted agents (Tc-99(m)-tilmanocept), and hybrid tracers adding fluorescence to radioguidance (ICG-Tc-99(m)-nanocolloid) as well as targeting hypoxia-induced carbonic anhydrase IX (CAIX) will be covered. Furthermore, future outlooks on the implementation of gold nanoparticles (AuNP's), but also technical advances in improved radiotracer detection by hybrid gamma devices will be discussed.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Stage and cancer-specific mortality differ within specific Asian ethnic groups for upper tract urothelial carcinoma: North American population-based study

Objectives: To examine the effect of specific Asian ethnic subgroups on stage at presentation and cancer-specific mortality in non-metastatic upper tract urothelial carcinoma among North American upper tract urothelial carcinoma Asian patients treated with radical nephroureterectomy. Methods: We relied on the Surveillance, Epidemiology and End Results database, from 2004 to 2016. Kaplan–Meier plots and multivariable Cox regression models predicting cancer-specific mortality were used. Results: Of 584 upper tract urothelial carcinoma patients, 173 (29.6%) were Chinese versus 130 (22.3%) Japanese versus 68 (11.6%) Korean versus 64 (11.0%) Filipino versus 40 (6.8%) Vietnamese versus 109 (18.7%) other. Vietnamese and Chinese patients showed the highest rates of T4N0M0 and/or T1–4N1–2M0 (25.0% and 18.5%, respectively), relative to other Asian ethnic subgroups. In Kaplan–Meier plots, Vietnamese patients showed the highest cancer-specific mortality rate. In multivariable models, Vietnamese ethnicity also independently predicted higher cancer-specific mortality (hazard ratio 2.15, P = 0.02 and hazard ratio 1.96, P = 0.03), relative to Japanese and Chinese patients. All other Asian ethnic subgroups showed similar cancer-specific mortality patterns. Conclusion: Vietnamese and Chinese patients are at a stage disadvantage at upper tract urothelial carcinoma diagnosis, relative to all other Asian ethnicities. After adjustment for stage, only Vietnamese patients showed a survival disadvantage relative to all other Asian ethnic subgroups. As a result, it appears that Vietnamese patients not only present at a higher upper tract urothelial carcinoma stage, but additionally appear to harbor upper tract urothelial carcinoma that progresses at a faster rate than in other Asian ethnic subgroups

Contemporary analysis of the effect of marital status on survival in upper tract urothelial carcinoma patients treated with radical nephroureterectomy: A population-based study

Purpose: Unmarried status is an established risk factor for worse cancer control outcomes in various malignancies. Moreover, several investigators observed worse outcomes in unmarried males, but not in females. This concept has not been tested in upper tract urothelial carcinoma and represents the topic of the study. Methods: Within Surveillance, Epidemiology and End Results database (2004–2016), we identified 8833 non-metastatic upper tract urothelial carcinoma patients treated with radical nephroureterectomy (5208 males vs. 3625 females). Kaplan Meier plots and multivariable Cox regression models predicting overall mortality, other-cause mortality and cancer-specific mortality were used. Results: Overall, 1323 males (25.4%) and 1986 females (54.8%) were unmarried. Except for lower rates of chemotherapy in unmarried males (15.6 vs. 19.6%, P = 0.001) and unmarried females (13.8 vs. 23.6%, P < 0.001), no clinically meaningful differences were recorded between males and females. In multivariable Cox regression models, unmarried status was an independent predictor of higher overall mortality in both males (Hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.19–1.48, P < 0.001) and females (HR: 1.13, 95%CI: 1.00–1.27, P = 0.04), as well as of higher other-cause mortality in both males (HR: 1.53, 95%CI: 1.26–1.84,P < 0.001) and females (HR: 1.43, 95%CI: 1.15–1.78,P < 0.01). However, higher cancer-specific mortality was only recorded in unmarried males (HR: 1.24, 95%CI: 1.08–1.42, P < 0.01), but not in females (HR: 1.02, 95%CI: 0.89–1.17, P = 0.7). Conclusion: Unmarried status is a marker of worse survival in both males and females and should be flagged as an important risk factor at diagnosis, in both sexes. In consequence, unmarried patients represent candidate for interventions aimed at decreasing the survival gap relative to married counterparts

Race/Ethnicity Determines Life Expectancy in Surgically Treated T1aN0M0 Renal Cell Carcinoma Patients

Background: Life expectancy (LE) is an important consideration in the clinical decision-making for T1aN0M0 renal cell cancer (RCC) patients. Objective: To test the effect of race/ethnicity (Caucasian, African American, Hispanic/Latino, and Asian) on LE predictions from Social Security Administration (SSA) life tables in male and female T1aN0M0 RCC patients. Design, setting, and participants: We relied on the Surveillance, Epidemiology, and End Results database. Intervention: Radical nephrectomy (RN) and partial nephrectomy (PN). Outcome measurements and statistical analysis: Five-year and 10-yr observed overall survival (OS) of pT1aN0M0 RCC patients treated between 2004 and 2006 were compared with the LE predicted from SSA life tables. We repeated the comparison in a more contemporary cohort (2009–2011), with 5-yr follow-up and higher PN rates. Results and limitations: In the 2004–2006 cohort, PN rate was 40.7%. OS followed the predicted LE in Caucasians, Hispanics/Latinos, and Asians, but not in African Americans, in whom 5-yr OS rates were 5.0% (male) and 8.7% (female) and 10-yr rates were 4.2% (male) and 11.1% (female) lower than predicted. In the 2009–2011 cohort, PN rate was 59.4%. Same observations were made for OS versus predicted LE in Caucasians, Hispanics/Latinos, and Asians. In African Americans, 5-yr OS rates were 1.5% (male) and 4.9% (female) lower than predicted. Conclusions: In RN- or PN-treated pT1aN0M0 RCC patients, LE predictions closely approximated OS of Caucasians, Hispanics/Latinos, and Asians. In African-American patients, SSA life tables overestimated LE, more in females than in males. The limitations of our study are its retrospective nature, its validity for US patients only, and the under-representation of racial/ethnic minorities. Patient summary: Social Security Administration life tables can be used to estimate long-term life expectancy in patients who are surgically treated for renal cancer (≤4 cm). However, while for Caucasians, Hispanics/Latinos, and Asians, the prediction performs well, life expectancy of African Americans is generally overestimated by life table predictions. Take Home Message: In the clinical decision-making process for T1aN0M0 renal cell cancer patients eligible for radical or partial nephrectomy, the important influence of patient sex and race/ethnicity on life expectancy should be taken into account, when using Social Security Administration life tables

External beam radiotherapy and radical prostatectomy are associated with better survival in Asian prostate cancer patients

Objectives: To test the effect of race/ethnicity on cancer-specific mortality after radical prostatectomy or external beam radiotherapy in localized prostate cancer patients. Methods: In the Surveillance, Epidemiology and End Results database 2004–2016, we identified intermediate-risk and high-risk white (n&nbsp;=&nbsp;151&nbsp;632), Asian (n&nbsp;=&nbsp;11&nbsp;189), Hispanic/Latino (n&nbsp;=&nbsp;20&nbsp;077) and African American (n&nbsp;=&nbsp;32&nbsp;550) localized prostate cancer patients, treated with external beam radiotherapy or radical prostatectomy. Race/ethnicity-stratified cancer-specific mortality analyses relied on competing risks regression, after propensity score matching for patient and cancer characteristics. Results: Compared with white patients, Asian intermediate- and high-risk external beam radiotherapy patients showed lower cancer-specific mortality (hazard ratio 0.58 and 0.70, respectively, both P&nbsp;≤&nbsp;0.02). Additionally, Asian high-risk radical prostatectomy patients also showed lower cancer-specific mortality than white patients (hazard ratio 0.72, P&nbsp;=&nbsp;0.04), but not Asian intermediate-risk radical prostatectomy patients (P&nbsp;=&nbsp;0.08). Conversely, compared with white patients, African American intermediate-risk radical prostatectomy patients showed higher cancer-specific mortality (hazard ratio 1.36, P&nbsp;=&nbsp;0.01), but not African American high-risk radical prostatectomy or intermediate- and high-risk external beam radiotherapy patients (all P&nbsp;≥&nbsp;0.2). Finally, compared with white people, no cancer-specific mortality differences were recorded for Hispanic/Latino patients after external beam radiotherapy or radical prostatectomy, in both risk levels (P&nbsp;≥&nbsp;0.2). Conclusions: Relative to white patients, an important cancer-specific mortality advantage applies to intermediate-risk and high-risk Asian prostate cancer patients treated with external beam radiotherapy, and to high-risk Asian patients treated with radical prostatectomy. These observations should be considered in pretreatment risk stratification and decision-making

Survival benefit of chemotherapy in a contemporary cohort of metastatic urachal carcinoma

Background: We relied on the most contemporary Surveillance, Epidemiology, and End Results (SEER) database and tested the hypothesis that chemotherapy may improve survival in metastatic urachal carcinoma (m-UraC). Material and Methods: Within the SEER database (2004\u20132016), we identified m-UraC patients aged 65 18 years. Propensity score matching (PSM: cystectomy status, age and sex), Kaplan-Meier plots, cumulative incidence plots, Cox regression models and competing risks regression (CRR) models addressed overall mortality (OM) and cancer-specific mortality (CSM). Results: Overall, 274 m-UraC patients were identified with a median age of 70 years. Most were male (66%) and Caucasian (72%). Overall, 32% received chemotherapy. Chemotherapy-exposed patients were younger (62 vs. 73 years, p&lt;0.001) and more frequently underwent cystectomy (19 vs. 8%, P = 0.014). In 274 m-UraC patients, median OM and CSM were 6 (4 \u201310) months and 8 (6 \u201314) months, respectively. After 1:1 PSM, chemotherapy-exposed patients exhibited lower OM (median 16 vs. 3 months; multivariable HR 0.38, P &lt;0.001) and lower CSM (median 17 vs. 4 months; multivariable CRR HR 0.52, P = 0.001). The association between chemotherapy and better survival was even stronger in younger ( 6470 years) patients (OM HR: 0.23, P &lt;0.001; CSM CRR HR: 0.42, P = 0.001), but not in older ( 6571 years) patients (OM HR: 0.61, P = 0.2; CSM CRR HR: 1.02, P = 1), after PSM and multivariable adjustments. Conclusion: Overall, we validated the very aggressive nature of UraC, when distant metastases are present, and observed that m-UraC patients exposed to chemotherapy exhibited lower OM and CSM

Immuno-oncology therapy in metastatic bladder cancer: A systematic review and network meta-analysis

reserved15Context: Three first line and three second-line clinical trials tested the effect of immunotherapy (IO) relative to standard chemotherapy (CT) on overall survival. However, network meta-analysis-based comparisons have not yet been presented. We addressed this void. Objective: To provide comparisons of overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), stable disease (SD), objective response rates (ORR), disease control rates (DCR) and adverse events (AEs) associated with 1st and 2nd line IO-based regimens. Materials and methods: PubMed was searched for phase III randomized controlled trials from 2016 to 2021, including conference abstracts. We identified three first line [IMvigor130 (atezolizumab + CT vs atezolizumab vs CT), DANUBE (durvalumab vs durvalumab + tremelimumab vs CT), and KEYNOTE-361 (pembrolizumab + CT vs pembrolizumab vs CT)] and two second line [KEYNOTE-045 (pembrolizumab vs CT) and IMvigor211 (atezolizumab vs CT)] RCTs. Results: Overall, 3255 and 1452 patients were respectively included in the first- and second-line settings. In 1st line setting, compared with CT, no IO-based regimen exhibited survival benefit. However, all exclusive IO regimens resulted in lower rates of grade 3+ AEs. In 2nd line setting, compared with CT, only pembrolizumab improved OS benefit. Conversely, atezolizumab only showed OS benefit in exploratory analyses. Compared to second-line CT, no experimental regimen (atezolizumab or pembrolizumab) exhibited statistically significant ORR benefit. Both pembrolizumab and atezolizumab resulted in lower rates of grade 3+ AEs compared to 2nd line CT. Conclusions: In metastatic UC, IO-based regimens do not hold a survival benefit relative to CT in 1st line setting. However, pembrolizumab holds a survival benefit in 2nd line compared to CT. Several IO-based clinical trials are ongoing and will provide more and possibly better treatment alternatives for locally advanced and metastatic UC.mixedChierigo F.; Wenzel M.; Wurnschimmel C.; Flammia R.S.; Horlemann B.; Tian Z.; Saad F.; Chun F.K.H.; Tilki D.; Shariat S.F.; Gallucci M.; Borghesi M.; Suardi N.; Terrone C.; Karakiewicz P.I.Chierigo, F.; Wenzel, M.; Wurnschimmel, C.; Flammia, R. S.; Horlemann, B.; Tian, Z.; Saad, F.; Chun, F. K. H.; Tilki, D.; Shariat, S. F.; Gallucci, M.; Borghesi, M.; Suardi, N.; Terrone, C.; Karakiewicz, P. I

Presence of biopsy Gleason pattern 5 + 3 is associated with higher mortality after radical prostatectomy but not after external beam radiotherapy compared to other Gleason Grade Group IV patterns+

none16Background: We hypothesized that Gleason Grade Group (GGG) IV patients treated with radical prostatectomy (RP) or external beam radiotherapy (EBRT) exhibit different cancer-specific mortality (CSM) rates according to underlying Gleason patterns (GP): 4 + 4 versus 3 + 5 versus 5 + 3. Materials and Methods: We identified all GGG IV patients treated with either RP or EBRT within the Surveillance, Epidemiology, and End Results 2004–2016 database. The effect of biopsy GP on CSM (3 + 5 vs. 4 + 4 vs. 5 + 3) was tested in Kaplan–Meier and multivariable competing risks regression models (adjusted for PSA, age at diagnosis, cT-, and cN-stage). Results: Of 26,458 GGG IV patients, 14,203 (53.7%) were treated with EBRT and 12,255 (46.3%) with RP. Of RP patients, 15.3 versus 81.2 versus 3.4% exhibited biopsy GP 3 + 5 versus 4 + 4 versus 5 + 3 and respective 10-year CSM rates were 6.5 versus 6.2 versus 12.6% (p &lt;.001). In multivariable analyses addressing RP patients, GP 5 + 3 was associated with two-fold higher CSM rate than GP 4 + 4 (p &lt;.001), but not GP 3 + 5 (p =.1). Of EBRT patients, 7.6 versus 89.8 versus 2.6% exhibited biopsy GP 3 + 5 versus 4 + 4 versus 5 + 3 and respective 10-year CSM rates were 12.2 versus 13.8 versus 17.8% (p &lt;.001). In multivariable analyses addressing EBRT patients, no CSM differences according to GP were observed (all p ≥.4). Conclusion: In GGG IV RP candidates, the presence of biopsy GP 5 + 3 purports a significantly higher CSM than in GP 4 + 4 or 3 + 5. In GGG IV EBRT candidates, no significant CSM differences according to GP were recorded.noneWurnschimmel C.; Wenzel M.; Chierigo F.; Flammia R.S.; Mori K.; Tian Z.; Shariat S.F.; Saad F.; Briganti A.; Suardi N.; Terrone C.; Gallucci M.; Chun F.K.H.; Tilki D.; Graefen M.; Karakiewicz P.I.Wurnschimmel, C.; Wenzel, M.; Chierigo, F.; Flammia, R. S.; Mori, K.; Tian, Z.; Shariat, S. F.; Saad, F.; Briganti, A.; Suardi, N.; Terrone, C.; Gallucci, M.; Chun, F. K. H.; Tilki, D.; Graefen, M.; Karakiewicz, P. I