Testicular Cancer Treatments and Sexuality: A Narrative Review.

The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing the patient different treatment approaches according to histology and tumor stage. Currently, physicians usually prioritize oncological outcomes over sexual outcomes and quality of life, considering as a first aim the overall survival of the patients; however, differently from other neoplasms, quality of life is still strongly affected among TC patients, and sexual outcomes are frequently compromised after each TC treatment. Several studies have suggested that each treatment approach may be associated with sexual dysfunctions, including erectile dysfunction, ejaculatory disorders, fertility issues, and hormonal changes. Since testicular cancer patients are more frequently young men, the subject of this work is substantial and should be analyzed in detail to help specialists in the management of this disease. The aim of the current narrative review is to generally describe every treatment for TC, including surgery, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, and to establish which sexual dysfunction may be specifically associated with each therapy.

The Role of PSMA PET Imaging in the Classification of the Risk of Prostate Cancer Patients: A Systematic Review on the Insights to Guide an Active Surveillance Approach.

BACKGROUND: active surveillance (AS) is a suitable strategy for patients with prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging is an established tool used to assess PCa. The aim of this review was to evaluate the role of PSMA imaging to guide correct risk-based classification and the AS approach in PCa patients. METHODS: The Scopus, Embase, Web of Science, Cochrane Library, and PubMed/MEDLINE databases were screened to find relevant published articles. RESULTS: 1774 articles were revealed with the literature search. A total of 1764 articles were excluded after applying exclusion criteria (data not within the field of interest, preclinical papers, conference proceedings, reviews, or editorials). Ten studies were finally included in the review, revealing that PSMA PET could have the ability to guide risk-based classification of PCa and the choice of AS, and to guide the execution of biopsies for the research of high-grade PCa, therefore precluding AS. CONCLUSION: this systematic review underlined a possible role of PSMA PET imaging in patients with PCa by correctly re-classifying them on the basis of their risk and guiding AS.

The CDK Inhibitor Dinaciclib Improves Cisplatin Response in Nonseminomatous Testicular Cancer: A Preclinical Study.

BACKGROUND: Most patients with testicular germ cell tumors (GCTs) are treated with cisplatin (CP)-based chemotherapy. However, some of them may develop CP resistance and therefore represent a clinical challenge. Cyclin-dependent kinase 5 (CDK5) is involved in chemotherapy resistance in different types of cancer. Here, we investigated the possible role of CDK5 and other CDKs targeted by dinaciclib in nonseminoma cell models (both CP-sensitive and CP-resistant), evaluating the potential of the CDK inhibitor dinaciclib as a single/combined agent for the treatment of advanced/metastatic testicular cancer (TC). METHODS: The effects of dinaciclib and CP on sensitive and resistant NT2/D1 and NCCIT cell viability and proliferation were evaluated using MTT assays and direct count methods. Flow cytometry cell-cycle analysis was performed. The protein expression was assessed via Western blotting. The in vivo experiments were conducted in zebrafish embryos xenografted with TC cells. RESULTS: Among all the CDKs analyzed, CDK5 protein expression was significantly higher in CP-resistant models. Dinaciclib reduced the cell viability and proliferation in each cell model, inducing changes in cell-cycle distribution. In drug combination experiments, dinaciclib enhances the CP effect both in vitro and in the zebrafish model. CONCLUSIONS: Dinaciclib, when combined with CP, could be useful for improving nonseminoma TC response to CP.

Pathological Complete Response to Pembrolizumab plus Axitinib Combination following Serious Immune-Related Adverse Events in an Advanced Renal Cell Carcinoma Patient with a History of Rheumatoid Arthritis.

Immune checkpoint inhibitors (ICIs)-based combinations have improved survival outcomes of advanced renal cell carcinoma (RCC) patients and are currently recommended as first-line treatment options. Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) of unknown etiology characterized by a chronic inflammatory process involving joints and extra-articular organs. Patients with AD are usually excluded from large randomized clinical trials investigating immunotherapeutic drugs. Therefore, little is known about clinical outcomes of patients with a history of RA treated with ICIs in real-world practice. In the present study, we report the clinical outcome of an advanced RCC patient with a history of RA treated with pembrolizumab in combination with axitinib. The patient experienced serious immune-related adverse events (irAEs) and achieved pathological complete response following only one ICI administration. Our case report shows that ICI-based combinations can be administered efficaciously in advanced RCC patients with a history of AD. However, a close monitoring of these patients is required, given the risk of irAEs and clinical exacerbations of symptoms associated with the preexisting AD. Moreover, prospective clinical data are needed to assess the hypothesis of a correlation between the onset of irAEs and AD flares and responses and survival outcomes to ICIs.

Survival of patients with clear cell renal carcinoma according to number and location of organ-specific metastatic sites.

BACKGROUND: The prognostic significance of number and location of organ-specific metastatic sites in treated metastatic clear cell renal carcinoma (ccmRCC) patients is object of debate. The current study aimed to test the association between number and location of organ-specific metastatic sites and overall survival (OS) in ccmRCC. MATERIALS AND METHODS: Within Surveillance, Epidemiology and End Results database (2010-2018), all ccmRCC patients treated with cytoreductive nephrectomy and/or systemic therapy were identified. Kaplan-Meier plots and Cox regression models focused on: A). number of organ-specific metastatic sites: solitary vs. 2 vs. 3 or more; B). solitary organ-specific metastatic sites (lung vs. bone vs. liver vs. brain); C). combinations of 2 and 3 or more different organ-specific metastatic sites. RESULTS: Of 4,527 patients (median OS: 19 months), 3,054 (67%) harbored solitary organ-specific metastatic sites (27 months) vs. 1,153 (25%) combinations of 2 different organ-specific metastatic sites (12 months) vs. 320 (8%) combinations of 3 or more different organ-specific metastatic sites (7 months). In patients with solitary organ-specific metastatic sites, bone metastases portended the longest median OS (median OS: 31 months) vs. liver metastases portended the shortest median OS (16 months). Both were independent predictors of OS (multivariable hazard ratio, bone: 0.87; liver: 1.21). Median OS was similarly poor in patients with combinations of 2 different organ-specific metastatic sites (9-13 months), regardless of their location. The same pattern applied to patients with combinations of 3 or more different organ-specific metastatic sites (6-7 months). CONCLUSIONS: Solitary organ-specific metastatic sites portend the most favorable OS (16-31 months). Solitary bone metastases yield the longest vs. liver metastases the shortest OS. Invariably poor OS applies to combinations of 2 (9-13 months), as well as 3 or more different organ-specific metastatic sites (6-7 months), regardless of their location.

Diagnostic accuracy of fully hybrid [68Ga]Ga-PSMA-11 PET/MRI and [68Ga]Ga-RM2 PET/MRI in patients with biochemically recurrent prostate cancer: a prospective single-center phase II clinical trial.

PURPOSE: To compare the diagnostic accuracy and detection rates of PET/MRI with [68Ga]Ga-PSMA-11 and [68Ga]Ga-M2 in patients with biochemical recurrence of prostate cancer (PCa). METHODS: Sixty patients were enrolled in this prospective single-center phase II clinical trial from June 2020 to October 2022. Forty-four/60 completed all study examinations and were available at follow-up (median: 22.8 months, range: 6-31.5 months). Two nuclear medicine physicians analyzed PET images and two radiologists interpreted MRI; images were then re-examined to produce an integrated PET/MRI report for both [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 examinations. A composite reference standard including histological specimens, response to treatment, and conventional imaging gathered during follow-up was used to validate imaging findings. Detection rates, accuracy, sensitivity, specificity, positive, and negative predictive value were assessed. McNemar's test was used to compare sensitivity and specificity on a per-patient base and detection rate on a per-region base. Prostate bed, locoregional lymph nodes, non-skeletal distant metastases, and bone metastases were considered. p-value significance was defined below the 0.05 level after correction for multiple testing. RESULTS: Patients' median age was 69.8 years (interquartile range (IQR): 61.8-75.1) and median PSA level at time of imaging was 0.53 ng/mL (IQR: 0.33-2.04). During follow-up, evidence of recurrence was observed in 31/44 patients. Combining MRI with [68Ga]Ga-PSMA-11 PET and [68Ga]Ga-RM2 PET resulted in sensitivity = 100% and 93.5% and specificity of 69.2% and 69.2%, respectively. When considering the individual imaging modalities, [68Ga]Ga-RM2 PET showed lower sensitivity compared to [68Ga]Ga-PSMA-11 PET and MRI (61.3% vs 83.9% and 87.1%, p = 0.046 and 0.043, respectively), while specificity was comparable among the imaging modalities (100% vs 84.6% and 69.2%, p = 0.479 and 0.134, respectively). CONCLUSION: This study brings further evidence on the utility of fully hybrid PET/MRI for disease characterization in patients with biochemically recurrent PCa. Imaging with [68Ga]Ga-PSMA-11 PET showed high sensitivity, while the utility of [68Ga]Ga-RM2 PET in absence of a simultaneous whole-body/multiparametric MRI remains to be determined.

Overall Survival of Metastatic Prostate Cancer Patients According to Location of Visceral Metastatic Sites.

INTRODUCTION: It is unknown whether specific locations of visceral metastatic sites affect overall survival (OS) of metastatic prostate cancer (mPCa) patients. We tested the association between specific locations of visceral metastatic sites and OS in mPCa patients. MATERIALS AND METHODS: Within Surveillance, Epidemiology and End Results database (2010-2016), survival analyses relied on specific locations of visceral metastases: lung only vs. liver only vs. brain only vs. ≥2 visceral sites. Kaplan-Meier plots and Cox regression models were fitted. RESULTS: Of 1827 patients, 1044 (57%) harbored lung only visceral metastases vs. 457 (25%) liver only vs. 131 (7%) brain only vs. 195 (11%) ≥2 visceral sites. Median OS was 22 months in all patients vs. 33 months in lung only vs. 15 months in liver only vs. 16 months in brain only vs. 15 months in patients with ≥2 visceral sites. Highest OS was recorded in lung only visceral metastases patients, especially when concomitant nonvisceral metastases were located in lymph nodes only (median OS 57 months) vs. bone only (26 months) vs. lymph nodes and bone (28 months). Liver only, brain only or ≥2 visceral sites exhibited poor OS, regardless of concomitant nonvisceral metastases type (median OS from 13 to 19 months). CONCLUSION: In mPCa patients, lung only visceral metastases, especially when associated with lymph node only nonvisceral metastases, portend the best prognosis. Conversely, visceral metastatic sites other than lung portend poor prognosis, regardless of concomitant nonvisceral metastases type.

Positive Surgical Margins After Anterior Robot-assisted Radical Prostatectomy: Assessing the Learning Curve in a Multi-institutional Collaboration.

BACKGROUND: The learning curve for robot-assisted radical prostatectomy (RARP) remains controversial, with prior studies showing that, in contrast with evidence on open and laparoscopic radical prostatectomy, biochemical recurrence rates of experienced versus inexperienced surgeons did not differ. OBJECTIVE: To characterize the learning curve for positive surgical margins (PSMs) after RARP. DESIGN, SETTING, AND PARTICIPANTS: We analyzed the data of 13 090 patients with prostate cancer undergoing RARP by one of 74 surgeons from ten institutions in Europe and North America between 2003 and 2022. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable models were used to assess the association between surgeon experience at the time of each patient's operation and PSMs after surgery, with adjustment for preoperative prostate-specific antigen level, grade, stage, and year of surgery. Surgeon experience was coded as the number of robotic radical prostatectomies done by the surgeon before the index patient's operation. RESULTS AND LIMITATIONS: Overall, 2838 (22%) men had PSMs on final pathology. After adjusting for case mix, we found a significant, nonlinear association between surgical experience and probability of PSMs after surgery, with a lower risk of PSMs for greater surgeon experience (p < 0.0001). The probabilities of PSMs for a patient treated by a surgeon with ten, 250, 500, and 2000 prior robotic procedures were 26%, 21%, 18%, and 14%, respectively (absolute risk difference between ten and 2000 procedures: 11%; 95% confidence interval: 9%, 14%). Similar results were found after stratifying patients according to extracapsular extension at final pathology. Results were also unaltered after excluding surgeons who had moved between institutions. CONCLUSIONS: While we characterized the learning curve for PSMs after RARP, the relative contribution of surgical learning to the achievement of optimal outcomes remains controversial. Future investigations should focus on what experienced surgeons do to avoid positive margins and should explore the relationship between learning, margin rate, and biochemical recurrence. Understanding what margins affect recurrence and whether these margins are trainable or a result of other factors may shed light on where to focus future efforts in surgical education. PATIENT SUMMARY: In patients receiving robotic radical prostatectomy for prostate cancer, we characterized the learning curve for positive margins. The risk of surgical margins decreased progressively with increasing experience, and plateaued around the 500th procedure. Understanding what margins affect recurrence and whether these margins are trainable or a result of other factors has implications for surgeons and patients, and it may shed light on where to focus future efforts in surgical education.

PET/CT and Conventional Imaging for the Assessment of Neuroendocrine Prostate Cancer: A Systematic Review.

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a rare neoplasm, and the role of both conventional imaging (CI) and positron emission tomography/computed tomography (PET/CT) for its assessment has not been clearly evaluated and demonstrated. The aim of this systematic review was to analyze the diagnostic performances of these imaging modalities in this setting. METHODS: A wide literature search of the PubMed/MEDLINE, Scopus, and Web of Science databases was made to find relevant published articles about the role of CI and PET/CT for the evaluation of NEPC. RESULTS: 13 studies were included in the systematic review. PET/CT imaging with different radiopharmaceuticals has been evaluated in many studies (10) compared to CI (3 studies), which has only a limited role in NEPC. Focusing on PET/CT, a study used [18F]FDG, labeled somatostatin analogs were used in 5 cases, a study used [68Ga]Ga-FAPI-04, [68Ga]Ga-PSMA-11 was evaluated in a single case, and two works used different tracers. CONCLUSION: Published data on the role of PET/CT for the assessment of NEPC are limited. At present, it is still uncertain which tracer performs best, and although [18F]FDG has been evaluated and seems to offer some advantages in availability and clinical staging, other tracers may be more useful to understand tumor biology or identify targets for subsequent radioligand therapy. Further research is therefore desirable. In contrast, data are still limited to draw a final conclusion on the role and the specific characteristics of CI in this rare form of neoplasm, and therefore, more studies are needed in this setting.

Racial/ethnic disparities in the distribution and effect of type and number of high-risk criteria on mortality in prostate cancer patients treated with radiotherapy.

Objective: To assess differences in the distribution of type and number of D'Amico high-risk criteria (DHRCs) according to race/ethnicity (R/E) and their effect on cancer-specific mortality (CSM) in prostate cancer (PCa) patients treated with external beam radiotherapy (RT). Methods: In the SEER database (2004-2016), we identified 31,002 PCa patients treated with RT with at least one DHRCs, namely PSA >20 ng/dL, biopsy Gleason Grade Group 4-5, and clinical T stage ≥T2c. Competing risks regression (CRR) model tested the association between DHRCs and 5-year CSM in all R/E subgroups. Results: Of 31,002 patients, 20,894 (67%) were Caucasian, 5256 (17%) were African American, 2868 (9.3%) were Hispanic-Latino, and 1984 (6.4%) were Asian. The distributions of individual DHRCs and combinations of two DHRCs differed according to R/E, but not for the combination of three DHRCs. The effect related to the presence of a single DHRC, and combinations of two or three DHRCs on absolute CSM rates was lowest in Asians (1.2-6.8%), followed by in African Americans (2.3-12.2%) and Caucasians (2.3-12.1%), and highest in Hispanic/Latinos (1.7-13.8%). However, the opposite effect was observed in CRR, where hazard ratios were highest in Asians vs. other R/Es: Asians 1.00-2.59 vs. others 0.5-1.83 for one DHRC, Asians 3.4-4.75 vs. others 0.66-3.66 for two DHRCs, and Asians 7.22 vs. others 3.03-4.99 for all three DHRCs. Conclusions: R/E affects the proportions of DHRCs. Moreover, within the four examined R/E groups, the effect of DHRCs on absolute and relative CSM metrics also differed. Therefore, R/E-specific considerations may be warranted in high-risk PCa patients treated with RT.

The association of the type and number of D'Amico high-risk criteria with rates of pathologically non-organ-confined prostate cancer.

Introduction: The aim of this study was to assess the association between the type and number of D'Amico high-risk criteria (DHRCs) with rates of pathologically non-organ-confined (NOC) prostate cancer in patients treated with radical prostatectomy (RP) and pelvic lymphadenectomy (PLND). Material and methods: In the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 12961 RP and PLDN patients with at least one DHRC. We relied on descriptive statistics and multivariable logistic regression models. Results: Of 12 961 patients, 6135 (47%) exclusively harboured biopsy Gleason score (GS) 8-10, 3526 (27%) had clinical stage ≥T2c, and 1234 (9.5%) had prostate-specific antigen (PSA) >20 ng/mL. Only 1886 (15%) harboured any combination of 2 DHRCs. Finally, all 3 DHRCs were present in 180 (1.4%) patients. NOC rates increased from 32% for clinical T stage ≥T2c to 49% for either GS 8-10 only or PSA >20 ng/mL only and to 66-68% for any combination of 2 DHRCs, and to 84% for respectively all 3 DHRCs, which resulted in a multivariable logistic regression OR of 1.00, 2.01 (95% CI 1.85-2.19; p <0.001), 4.16 (95% CI 3.69-4.68; p <0.001), and 10.83 (95% CI 7.35-16.52; p <0.001), respectively. Conclusions: Our study indicates a stimulus-response effect according to the type and number of DHRCs. Hence, a formal risk-stratification within high-risk prostate cancer patients should be considered in clinical decision-making.

Radical cystectomy in bladder cancer patients previously treated for prostate cancer: Insights from a large European multicentric series.

INTRODUCTION: Previous radical prostatectomy (RP) for prostate cancer (PCa) might impair feasibility of radical cystectomy (RC) for bladder cancer (BCa). The current study addressed morbidity, operative time (OT), and length of stay (LOS) of RC, within the largest available series of patients with history of previous RP. MATERIALS AND METHODS: All patients previously submitted to RP for PCa and subsequently submitted to RC for BCa, at six high-volume European institutions between 2010 and 2019, were identified. Presence of either PCa or BCa metastases, RT as primary treatment for PCa, and palliative RC represented exclusion criteria. The quality criteria for accurate and comprehensive reporting of intra- and post-operative surgical outcomes, recommended by the European Association of Urology guidelines, were fulfilled. Multivariable logistic and Poisson regression analyses were performed. RESULTS: Overall, 140 RC patients with history of RP were identified. After RP, 69 (49%) patients received radiotherapy (RT) for PCa, either in adjuvant (n = 50, 36%) or salvage setting (n = 19, 13%). Median age-adjusted Charlson comorbidity index was 6 (IQR 5, 7). Median OT, estimated blood loss and LOS were, respectively, 300 min, 500 ml, and 16 days. Intra-operative transfusions rate was 47% (n = 65). One intra-operative complication occurred (EAUiaiC grade 2, perforation of the rectum managed with immediate repair). Eighty-two (59%) patients experienced a total of 107 post-operative complications during the hospital stay, and seven (5%) patients required hospital readmission. In multivariable regression analyses, RT for PCa was associated with higher risk of post-operative complications (odds ratio 1.82, p = 0.039), longer OT (incidence rate ratio 1.09, p < 0.001), and longer LOS (incidence rate ratio 1.24, p < 0.001). CONCLUSIONS: RC in patients with history of RP is feasible, albeit burdened by remarkable morbidity, even in centers of excellence. RT after RP for PCa portends worse surgical outcomes.

Adenocarcinoma of the Bladder: Assessment of Survival Advantage Associated With Radical Cystectomy and Comparison With Urothelial Bladder Cancer.

PURPOSE: To evaluate the association between radical cystectomy (RC) and cancer-specific mortality (CSM) in patients diagnosed with adenocarcinoma of the bladder (ACB). Moreover, to directly compare the survival advantage of RC between ACB vs. urothelial bladder cancer (UBC). MATERIALS AND METHODS: Non-metastatic muscle-invasive ACB and UBC patients were identified within Surveillance, Epidemiology, and End Results database (SEER 2000-2018). All analyses were stratified between RC vs. no-RC, in either organ-confined (OC: T2N0M0) or non-organ-confined (NOC: T3-4N0M0 or TanyN1-3M0) stages. Propensity score matching (PSM), cumulative incidence plots, competing risks regression (CRR) analyses, and 3 months' landmark analyses were performed. RESULTS: Overall, 1,005 ACB and 47,741 UBC patients were identified, of whom 475 (47%) and 19,499 (41%) were treated with RC, respectively. After PSM, comparison between RC vs. no-RC applied to 127 vs. 127 OC-ACB, 7,611 vs. 7,611 OC-UBC, 143 vs. 143 NOC-ACB, and 4,664 vs. 4,664 NOC-UBC patients. 36-month CSM rates in RC vs. no-RC patients were 14 vs. 44% in OC-ACB, 18 vs. 39% in OC-UBC, 49 vs. 66% in NOC-ACB, and 44 vs. 56% in NOC-UBC patients. In CRR analyses, the effect of RC on CSM yielded a hazard ratio of 0.37 in OC-ACB, of 0.45 in OC-UBC, of 0.65 in NOC-ACB and of 0.68 in NOC-UBC patients (all P values<0.001). Landmark analyses virtually perfectly replicated the results. CONCLUSIONS: In ACB, regardless of stage, RC is associated with lower CSM. The magnitude of this survival advantage was greater in ACB than in UBC, even after control for immortal time bias.

The association of type and number of high-risk criteria with cancer specific mortality in prostate cancer patients treated with radiotherapy.

BACKGROUND: To assess the association between of type and number of D'Amico high-risk criteria (DHRCs) with rates of cancer-specific mortality (CSM) in prostate cancer (PCa) patients treated with external beam radiotherapy (RT). METHODS: In the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 34,908 RT patients with at least one DHRCs, namely prostate-specific antigen (PSA) >20 ng/dL (hrPSA), biopsy Grade Group (hrGG) 4-5, clinical T stage (hrcT) ≥T2c. Multivariable Cox regression models (CRM), as well as competing risks regression (CRR) model, which further adjust for other cause mortality, tested the association between DHRCs and 5-year CSM. RESULTS: Of 34,908 patients, 14,777 (42%) exclusively harbored hrGG, 5641 (16%) hrPSA, 4390 (13%) had hrcT. Only 8238 (23.7%) harbored any combination of two DHRCs and 1862 (5.3%) had all three DHRCs. Five-year CSM rates ranged from 2.4% to 5.0% when any individual DHRC was present (hrcT, hrPSA, hrGG, in that order), versus 5.2% to 10.5% when two DHRCs were present (hrPSA+hrcT, hrcT+hrGG, hrPSA+hrGG, in that order) versus 14.4% when all three DHRCs were identified. In multivariable CRM hazard ratios relative to hrcT ranged from 1.07 to 1.76 for one DHRC, 2.20 to 3.83 for combinations of two DHRCs, and 5.11 for all three DHRCs. Multivariable CRR yielded to virtually the same results. CONCLUSIONS: Our study indicates a stimulus-response effect according to the type and number of DHRCs. This indicates potential for risk-stratification within HR PCa patients that could be applied in clinical decision making to increase or reduce treatment intensity.

The Association Between Cytoreductive Nephrectomy and Overall Survival in Metastatic Renal Cell Carcinoma with Primary Tumor Size ≤4 cm.

BACKGROUND: It is unknown whether the survival benefit of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) applies to patients with primary tumor size ≤4 cm. OBJECTIVE: To test the association between CN on overall survival (OS) of mRCC patients with primary tumor size ≤4 cm. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology, and End Results (SEER) database (2006-2018), all mRCC patients with primary tumor size ≤4 cm were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Propensity score matching (PSM), Kaplan-Meier plots, multivariable Cox regression analyses, and 6-mo landmark analyses addressed OS according to CN status. Sensitivity analyses examined specific populations of special interest: systemic therapy exposed versus naïve, clear-cell (ccmRCC) versus non-clear-cell (non-ccmRCC) mRCC histology, historical (2006-2012) versus contemporary (2013-2018), and young (≤65 yr) versus old (>65 yr) patients. RESULTS AND LIMITATIONS: Of 814 patients, 387 (48%) underwent CN. After PSM, the median OS was 44 versus 7 mo (Δ = 37 mo; p < 0.001) in CN versus no-CN patients. CN was associated with higher OS in overall population (multivariable hazard ratio [HR]: 0.30; p < 0.001) as well as in landmark analyses (HR: 0.39; p < 0.001). In all sensitivity analyses, CN was independently associated with higher OS: systemic therapy exposed, HR: 0.38; systemic therapy naïve, HR: 0.31; ccmRCC, HR: 0.29; non-ccmRCC, HR: 0.37; historical, HR: 0.31; contemporary, HR: 0.30; young, HR: 0.23; and old, HR: 0.39 (all p < 0.001). CONCLUSIONS: The current study validates the association between CN and higher OS in patients with primary tumor size ≤4 cm. This association is robust, controlled for immortal time bias, and valid across systemic treatment exposure, histologic subtypes, years of surgery, and patient age. PATIENT SUMMARY: In the current study, we tested the association between cytoreductive nephrectomy (CN) and overall survival in patients with metastatic renal cell carcinoma and small primary tumor size. We found a strong association between CN and survival, which persists even after several significant variations in patient and tumor characteristics.

Combining PSA and PET features to select candidates for salvage lymph node dissection in recurrent prostate cancer.

Objective: To evaluate the relationship between pre-operative PSA value, 68Ga-prostate-specific-membrane-antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). Patients and methods: The study included 164 patients diagnosed with ≤2 pelvic lymph-node recurrence(s) of PCa documented on 68Ga-PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high-volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (<0.5 ng/ml), low (0.5-0.99 ng/ml), moderate (1-1.5 ng/ml) and high (>1.5 ng/ml). Clinical recurrence (CR)-free survival after sLND was calculated using multivariable analyses and plotted over pre-operative PSA value. Results: Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre-operative PSA value, with highest rates for patients with pre-operative PSA > 1.5 ng/ml (pelvic-only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre-operative PSA was associated with PSA response (p < 0.0001). There were 51 CRs after sLND. After adjusting for confounders, we found a significant, non-linear relationship between PSA level at sLND and the 12-month CR-free survival (p < 0.0001), with the highest probability of freedom from CR for patients who received sLND at PSA level ≥1 ng/ml. Conclusions: In case of PET-detected nodal recurrences amenable to sLND, salvage surgery was associated with the highest short-term oncologic outcomes when performed in men with PSA ≥ 1 ng/ml. Awaiting confirmatory data from prospective trials, these findings may help physicians to optimize the timing for 68Ga-PSMA PET in biochemical recurrent PCa.

Effect of inguinal lymph node dissection in lymph node negative patients with squamous cell carcinoma of the penis.

INTRODUCTION: The survival benefit of inguinal lymph node dissection (ILND) vs no ILND in patients with squamous cell carcinoma of the penis (SCCP) and the absence of lymph node invasion is unclear. We addressed this uncertainty within the Surveillance, Epidemiology and End Results (SEER 2000-2018) database. MATERIAL AND METHODS: We identified lymph node negative SCCP patients who either underwent ILND (pN0) or clinical examination only (cN0). We tested for the effect of ILND vs no ILND on cancer-specific mortality (CSM) in Kaplan-Meier plots, univariable and multivariable Cox regression analyses, in a pT stage-specific fashion, before and after 1:3 propensity score matching (PSM). Sensitivity analyses were conducted according to historical and contemporary treatment periods as well as geographic regions. RESULTS: Of 2520 SCCP patients, 369 (15%) underwent ILND (pN0) vs 2151 (85%) did not (cN0). The pN0 vs cN0 distribution according to pT stages was as follows: 80 (7%) vs 1092 (93%) in pT1b, and 289 (21%) vs 1059 (79%) in pT2-3. At 36 months, CSM-free survival in pT2-3 stage was 89% in ILND vs 74% in no ILND patients (multivariable hazard ratio: 0.42, CI 0.30-0.60, p < 0.001). This result was confirmed in sensitivity analyses, and after 1:3 PSM. The same analyses could not be completed in pT1b stage due to insufficient number of observations and events. CONCLUSIONS: In pT2-3 stage SCCP, a significantly lower CSM was recorded in lymph node negative patients treated with ILND than in their clinical lymph node negative counterparts who did not undergo ILND.

The effect of chemotherapy in sarcomatoid bladder cancer patients treated with radical cystectomy.

INTRODUCTION: Data about the role of chemotherapy in sarcomatoid bladder cancer (SBC) are limited. We addressed the effect of chemotherapy in non-metastatic SBC patients treated with radical cystectomy (RC). METHODS: Using the Surveillance, Epidemiology, and End Results database (2001-2018), we identified 331 patients with non-metastatic muscle-invasive or higher SBC (T2-4N0-3M0). Kaplan-Meier plots and Cox regression models tested cancer-specific mortality (CSM ). Sample size and power analyses tested for power limitations. RESULTS: Of 331 SBC patients, 129 (38.9%) were exposed to chemotherapy. The rate of organ-confined stage (T2N0M0) was 33% in both chemotherapy-exposed and chemotherapy-naive patients. In the overall cohort, median CSM-free survival was 84 months (interquartile range [IQR] 21-NA) vs. 26 months (IQR 17-84) in chemotherapy exposed vs. chemotherapy-naive patients, respectively. In multivariable Cox regression models, chemotherapy was associated with lower CSM, without reaching statistical significance (hazard ratio [HR ] 0.72, confidence interval [CI] 0.51-1.01, p=0.054). In subgroup analyses, chemotherapy exposure in organ-confined (n=110) vs. non-organ-confined (n=221) patients resulted in a HR of 0.51 (p=0.12) vs. 0.77 (p=0.17), respectively. Power analyses, based on two-sided α=0.05, revealed values of 52%, 14%, and 43% in the entire population, organ-confined, and nonorgan-confined subgroups, respectively. CONCLUSIONS: In non-metastatic SBC treated with RC, the association between chemotherapy and lower CSM is particularly strong in organ-confined stage. A substantially larger cohort would be required to confirm the statistical significance of the recorded protective effect of chemotherapy.