Unmarried Status Effect on Stage at Presentation and Treatment Patterns in Non-Metastatic Upper Tract Urothelial Carcinoma Patients.

BACKGROUND: Unmarried status has been associated with higher proportions of locally advanced stage and lower treatment dose intensification rates in several urological and non-urological malignancies. However, no previous investigators focused on the association between unmarried status and advanced stage (T3-4N0-2) at presentation and lower nephroureterectomy (RNU) and systemic therapy (ST) rates in non-metastatic upper tract urothelial carcinoma (UTUC) patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, all non-metastatic UTUC patients were identified. Multivariable logistic regression models (LRMs) tested for differences in stage at presentation and treatment (RNU and ST) according to marital status (married vs unmarried), in a sex-specific fashion. RESULTS: Of all 8544 non-metastatic UTUC patients, 4748 (56%) were male vs 3190 (44%) were female. Of all 4748 male UTUC patients, 1191 (25%) were unmarried. Of all 3190 female UTUC patients, 1608 (50%) were unmarried. In multivariable LRMs predicting RNU, unmarried status was an independent predictor of lower RNU rates in male (Odds Ratio [OR]: 0.56; P < .001), but not in female (OR: 0.81; P = .1) non-metastatic UTUC patients. In multivariable LRMs predicting ST exposure, unmarried status was an independent predictor of lower ST rates in both male (OR:0.73; P = .03) and female (OR:0.64; P < .001) UTUC patients. In multivariable LRMs predicting locally advanced stage (T3-4N0-2), unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male (OR: 0.95; P = .5) or female (OR: 0.99; P = .9) UTUC patients. CONCLUSIONS: Unmarried male UTUC patients appear at risk of less being able to access RNU, relative to their married counterparts. Moreover, unmarried UTUC patients appear to less benefit from ST, regardless of sex. Conversely, unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male or female UTUC patients.

Decisional and prognostic impact of diagnostic ureteroscopy in high-risk upper tract urothelial carcinoma: A multi-institutional collaborative analysis (ROBUUST collaborative group).

BACKGROUND: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery. MATERIALS AND METHODS: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes. RESULTS: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (P = 0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (P = 0.6), and MFS (P = 0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality. CONCLUSIONS: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings.

Muscle-invasive bladder cancer in elderly and frail people: Is hypofractionated radiotherapy a feasible approach when no other local options are available?

AIM: The study aims to report the feasibility and safety of palliative hypofractionated radiotherapy targeting macroscopic bladder tumors in a monocentric cohort of frail and elderly bladder cancer patients not eligible for curative treatments. METHODS: Patients who underwent hypofractionated radiotherapy to the gross disease or to the tumor bed after transurethral resection of bladder tumor from 2017 to 2021 at the European Institute of Oncology IRCCS, were retrospectively considered. Schedules of treatment were 30 and 25 Gy in 5 fractions (both every other day, and consecutive days). Treatment response was evaluated with radiological investigation and/or cystoscopy. Toxicity assessment was carried out according to RTOG/EORTC v2.0 criteria. RESULTS: A total of 16 patients were included in the study, of these 11 received hypofractionated radiotherapy on the macroscopic target volume and five on the tumor bed after transurethral resection of bladder tumor. No grade (G) >2 acute toxicities were described after treatment for both groups. Only one patient in the group receiving radiotherapy on the macroscopic disease reported G4 GU late toxicity. Ten patients had available follow-up status (median FU time 18 months), of them six had complete response, one had stable disease, and three had progression of disease. The overall response rate and disease control rate were 60% and 70%, respectively. CONCLUSION: Our preliminary data demonstrate that palliative hypofractionated radiotherapy for bladder cancer in a frail and elderly population is technically feasible, with an acceptable toxicity profile. These outcomes emphasize the potential of this approach in a non-radical setting and could help to provide more solid indications in this underrepresented setting of patients.

Survival benefit of nephroureterectomy in systemic therapy exposed metastatic upper tract urinary urothelial carcinoma patients.

BACKGROUND: It is unknown whether the stage of the primary may influence the survival (OS) of metastatic upper tract urothelial carcinoma (mUTUC) patients treated with nephroureterectomy (NU) and systemic therapy (ST). We tested this hypothesis within a large-scale North American cohort. METHODS: Within Surveillance Epidemiology and End Results database 2000-2020, all mUTUC patients treated with ST+NU or with ST alone were identified. Kaplan-Maier plots depicted OS. Multivariable Cox regression (MCR) models tested for differences between ST+NU and ST alone predicting overall mortality (OM). All analyses were performed in localized (T1-T2) and then repeated in locally advanced (T3-T4) patients. RESULTS: Of all 728 mUTUC patients, 187 (26%) harbored T1-T2 vs 541 (74%) harbored T3-T4. In T1-T2 patients, the median OS was 20 months in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU independently predicted lower OM (HR 0.37, p < 0.001). Conversely, in T3-T4 patients, the median OS was 12 in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU was not independently associated with lower OM (HR 0.85, p = 0.1). CONCLUSIONS: In mUTUC patients, treated with ST, NU drastically improved survival in T1-T2 patients, even after strict methodological adjustments (multivariable and landmark analyses). However, this survival benefit did not apply to patients with locally more advanced disease (T3-T4).

Perioperative complications and in-hospital mortality in radical cystectomy patients with heart-valve replacement.

PURPOSE: To assess in-hospital mortality and complication rates after radical cystectomy (RC) in patients with history of heart-valve replacement. MATERIALS AND METHODS: Using the National Inpatient Sample (2000-2019), non-metastatic bladder cancer patients undergoing RC were stratified according to history of heart-valve replacement. Regression models (RM) predicted hospital outcomes. RESULTS: Of 25,535 RC patients, 250 (1.0%) harbored history of heart-valve replacement. Heart-valve replacement patients were older (median 74 vs. 70 years), more frequently male (87.2 vs. 80.6%), and more frequently had Charlson comorbidity index ≥3 (26.8 vs. 18.9%). In RC patients with history of heart-valve replacement vs. others, 62 vs. 2634 (24.8 vs. 10.4%) experienced cardiac complications, 28 vs. 3092 (11.2 vs. 12.2%) intraoperative complications, 11 vs. 1046 (4.4 vs. 4.1%) infections, <11 vs. 594 (<4.4 vs. 2.3%) perioperative bleeding, <11 vs. 699 (<4.4 vs. 2.8%) vascular complications, 74 vs. 6225 (29.6 vs. 24.7%) received blood transfusions, 37 vs. 3054 (14.8 vs. 12.1%) critical care therapy (CCT), and in-hospital mortality was recorded in <11 vs. 463 (<4.4 vs. 1.8%) patients. In multivariable RM, history of heart-valve replacement independently predicted cardiac complications (odds ratio 2.20, 95% confidence interval 1.62-2.99; p < 0.001). Conversely, no statically significant association was recorded between history of heart-valve replacement and length of stay, estimated hospital cost, intraoperative complications, perioperative bleeding, vascular complications, infections, blood transfusions, CCT use, and in-hospital mortality. CONCLUSIONS: Radical cystectomy patients with history of heart-valve replacement exhibited a 2.2-fold higher risk of cardiac complications, but no other complications, including no significantly higher in-hospital mortality.

Contemporary conditional cancer-specific survival rates in surgically treated nonmetastatic primary urethral carcinoma.

BACKGROUND: We examined the effect of disease-free interval (DFI) duration on cancer-specific mortality (CSM)-free survival, otherwise known as the effect of conditional survival, in radical urethrectomy nonmetastatic primary urethral carcinoma (PUC) patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, patient (age, sex, race/ethnicity, and marital status) and tumor (stage and histology) characteristics, as well as systemic therapy exposure status of nonmetastatic PUC patients were tabulated. Conditional survival estimates at 5-year were assessed based on DFI duration and according to stage at presentation (T1 -2N0 vs. T3-4N0-2). RESULTS: Of all 512 radical urethrectomy PUC patients, 278 (54%) harbored T1-2N0 stage versus 234 (46%) harbored T3-4N0-2 stage. In 512 PUC patients, 5-year CSM-free survival at initial diagnosis was 61.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 85.6%. In 278 T1-2N0 PUC patients, 5-year CSM-free survival at initial diagnosis was 68.4%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 86.9%. In 234 T3-4N0-2 PUC patients, 5-year CSM-free survival at initial diagnosis was 53.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 83.6%. CONCLUSIONS: Although intuitively, clinicians and patients are well aware of the concept that increasing DFI duration improves survival probability, only a few clinicians can accurately estimate the magnitude of survival improvement, as was done within the current study. Such information is crucial to survivors, especially in those diagnosed with rare malignancies, where the survival estimation according to DFI duration is even more challenging.

Surgically treated pelvic liposarcoma and leiomyosarcoma: The effect of tumor size on cancer-specific survival.

INTRODUCTION: In soft tissue pelvic liposarcoma and leiomyosarcoma, it is unknown whether a specific tumor size cut-off may help to better predict prognosis, defined as cancer-specific survival (CSS). We tested whether different tumor size cut-offs, could improve CSS prediction. MATERIALS AND METHODS: Surgically treated non-metastatic soft tissue pelvic sarcoma patients were identified (Surveillance, Epidemiology, and End Results 2004-2019). Kaplan-Meier plots, univariable and multivariable Cox-regression models and receiver operating characteristic-derived area under the curve (AUC) estimates were used. RESULTS: Overall, 672 (65 %) liposarcoma (median tumor size 11 cm, interquartile range [IQR] 7-16) and 367 (35 %) leiomyosarcoma (median tumor size 8 cm, IQR 5-12) patients were identified. The p-value derived ideal tumor size cut-off was 17.1 cm, in liposarcoma and 7.0 cm, in leiomyosarcoma. In liposarcoma, according to p-value derived cut-off, five-year CSS rates were 92 vs 83 % (≤17.1 vs > 17.1 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 83.8 to 86.8 % (Δ = 3 %). Similarly, among previously established cut-offs (5 vs 10 vs 15 cm), also 15 cm represented an independent predictor of CSS and improved prognostic ability from 83.8 to 87.0 % (Δ = 3.2 %). In leiomyosarcoma, according to p-value derived cut-off, five-year CSS rates were 86 vs 55 % (≤7.0 vs > 7.0 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 68.6 to 76.5 % (Δ = 7.9 %). CONCLUSIONS: In liposarcoma, the p-value derived tumor size cut-off was 17.1 cm vs 7.0 cm, in leiomyosarcoma. In both histologic subtypes, these cut-offs exhibited the optimal statistical characteristics (univariable, multivariable and AUC analyses). In liposarcoma, the 15 cm cut-off represented a valuable alternative.

Non-Surgical Bladder-Sparing Multimodal Management in Organ-Confined Urothelial Carcinoma of the Urinary Bladder: A Population-Based Analysis.

BACKGROUND: Trimodal therapy is considered the most validated bladder-sparing treatment in patients with organ-confined urothelial carcinoma of the urinary bladder (T2N0M0). However, scarce evidence exists regarding cancer-specific mortality (CSM) differences between trimodal therapy and other non-extirpative multimodal treatment options such as radiotherapy alone after transurethral resection (TURBT + RT) or chemotherapy alone after transurethral resection (TURBT + CT). METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified T2N0M0 patients treated with either trimodal therapy, TURBT + CT, or TURBT + RT. Temporal trends described trimodal therapy vs. TUBRT + CT vs. TURBT + RT use over time. Survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM according to each treatment modality. RESULTS: 3729 (40%) patients underwent TMT vs. 4030 (43%) TURBT + CT vs. 1599 (17%) TURBT + RT. Over time, trimodal therapy use (Estimating annual percent change, EAPC: +1.2%, p = 0.01) and TURBT + CT use increased (EAPC: +1.5%, p = 0.01). In MCR models, relative to trimodal therapy, TURBT + CT exhibited 1-14-fold higher CSM and TURBT + RT 1.68-fold higher CSM. In a subgroup analysis, TURBT + RT was associated with 1.42-fold higher CSM than TURBT + CT (p < 0.001). CONCLUSIONS: Strict trimodal therapy that includes both CT and RT after TURBT offers the best cancer control. When strict trimodal therapy cannot be delivered, cancer-specific survival outcomes appear to be superior with TURBT + chemotherapy compared to TURBT + RT.

Use of inpatient palliative care in metastatic urethral cancer.

BACKGROUND: In metastatic urethral cancer, temporal trends, and patterns of inpatient palliative care (IPC) use are unknown. METHODS: Relying on the National Inpatient Sample (2006-2019), metastatic urethral cancer patients were stratified according to IPC use. Estimated annual percentage changes (EAPC) analyses and multivariable logistic regression models (LRM) for the prediction of IPC use were fitted. RESULTS: Of 1,106 metastatic urethral cancer patients, 199 (18%) received IPC. IPC use increased from 5.8 to 28.0% over time in the overall cohort (EAPC +9.8%; P < 0.001), from <12.5 to 35.1% (EAPC +11.2%; P < 0.001), and from <12.5 to 24.7% (EAPC +9.4%; P = 0.01) in respectively females and males. Lowest IPC rates were recorded in the Midwest (13.5%) vs. highest in the South (22.5%). IPC patients were more frequently female (44 vs. 37%), and more frequently exhibited bone metastases (45 vs. 34%). In multivariable LRM, female sex (multivariable odds ratio [OR] 1.46, 95% confidence interval [CI] 1.05-2.02; P = 0.02), and bone metastases (OR 1.46, 95%CI 1.02-2.10; P = 0.04) independently predicted higher IPC rates. Conversely, hospitalization in the Midwest (OR 0.53, 95%CI 0.31-0.91; P = 0.02), and in the Northeast (OR 0.48, 95%CI 0.28-0.82; P = 0.01) were both associated with lower IPC use than hospitalization in the West. CONCLUSION: IPC use in metastatic urethral cancer increased from a marginal rate of 5.8% to as high as 28%. Ideally, differences according to sex, metastatic site, and region should be addressed to improve IPC use rates.

Photon vs proton hypofractionation in prostate cancer: A systematic review and meta-analysis.

BACKGROUND: High-level evidence on hypofractionated proton therapy (PT) for localized and locally advanced prostate cancer (PCa) patients is currently missing. The aim of this study is to provide a systematic literature review to compare the toxicity and effectiveness of curative radiotherapy with photon therapy (XRT) or PT in PCa. METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched up to April 2022. Men with a diagnosis of PCa who underwent curative hypofractionated RT treatment (PT or XRT) were included. Risk of grade (G) ≥ 2 acute and late genitourinary (GU) OR gastrointestinal (GI) toxicity were the primary outcomes of interest. Secondary outcomes were five-year biochemical relapse-free survival (b-RFS), clinical relapse-free, distant metastasis-free, and prostate cancer-specific survival. Heterogeneity between study-specific estimates was assessed using Chi-square statistics and measured with the I2 index (heterogeneity measure across studies). RESULTS: A total of 230 studies matched inclusion criteria and, due to overlapped populations, 160 were included in the present analysis. Significant lower rates of G ≥ 2 acute GI incidence (2 % vs 7 %) and improved 5-year biochemical relapse-free survival (95 % vs 91 %) were observed in the PT arm compared to XRT. PT benefits in 5-year biochemical relapse-free survival were maintained for the moderate hypofractionated arm (p-value 0.0122) and among patients in intermediate and low-risk classes (p-values < 0.0001 and 0.0368, respectively). No statistically relevant differences were found for the other considered outcomes. CONCLUSION: The present study supports that PT is safe and effective for localized PCa treatment, however, more data from RCTs are needed to draw solid evidence in this setting and further effort must be made to identify the patient subgroups that could benefit the most from PT.

Contemporary validation of cT1a vs. cT1b substaging of incidental prostate cancer.

OBJECTIVE: The cT1a vs. cT1b substratification was introduced in 1992 but never formally tested since. We tested the discriminative ability of cT1a vs. cT1b substaging on cancer-specific survival (CSS) in contemporary incidental prostate cancer (PCa) patients. DESIGN, SETTING AND PARTICIPANTS: Incidental (cT1a/cT1b) PCa patients were identified within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier estimates, as well as uni- and multivariable Cox regression models predicted CSS at five years. Subgroup analyses addressed CSS at five years according to active vs. no local treatment (NLT) as well as Gleason score sum (GS; 6 vs. 7 vs. ≥ 8). RESULTS AND LIMITATION: We identified a total of 5,155 incidental prostate cancer patients of which 3,035 (59%) were stage cT1a vs. 2,120 (41%) were stage cT1b. In all incidental PCa patients, CSS at five years was 95% (95% CI 0.94-0.96). In cT1a patients, CSS at five years was 98 vs. 90% in cT1b patients (p < 0.001). In multivariable Cox regression analyses, cT1b independently predicted 2.8-fold higher CSM than cT1a (HR 2.5, 95% CI 1.8-3.6, p < 0.001) for incidental PCa patients who underwent NLT. In subgroup analyses, cT1b represented an independent predictor of higher CSM in GS ≥ 8 (HR 3.0, 95% CI 1.4-6.2, p = 0.003), and GS 7 (HR 3.9, 95% CI 1.6-9.7 p = 0.002) patients who underwent NLT. For actively treated patients, cT1b was not independently associated with worse CSM. CONCLUSION: The historical subclassification of cT1a vs. cT1b in incidental PCa patients displayed a strong ability to discriminate CSS in contemporary GS 7 and GS ≥ 8 patients who underwent NLT. However, no statistically significant difference was recorded in actively treated patients. In consequence, the importance of the current substage stratification predominantly applies to GS ≥ 8 patients who undergo a non-active treatment approach.

The effect of married status on cancer-specific mortality in nonmetastatic pelvic liposarcoma patients according to sex.

BACKGROUND: In nonmetastatic pelvic liposarcoma patients, it is unknown whether married status is associated with better cancer-control outcome defined as cancer-specific mortality (CSM). We addressed this knowledge gap and hypothesized that married status is associated with lower CSM rates in both male and female patients. METHODS: Within the Surveillance, Epidemiology, and End Results database (2000-2020), nonmetastatic pelvic liposarcoma patients were identified. Kaplan-Meier plots and univariable and multivariable Cox regression models (CRMs) predicting CSM according to marital status were used in the overall cohort and in male and female subgroups. RESULTS: Of 1078 liposarcoma patients, 764 (71%) were male and 314 (29%) female. Of 764 male patients, 542 (71%) were married. Conversely, of 314 female patients, 192 (61%) were married. In the overall cohort, 5-year cancer-specific mortality-free survival (CSM-FS) rates were 89% for married versus 83% for unmarried patients (Δ = 6%). In multivariable CRMs, married status did not independently predict lower CSM (hazard ratio [HR]: 0.74, p = 0.06). In males, 5-year CSM-FS rates were 89% for married versus 86% for unmarried patients (Δ = 3%). In multivariable CRMs, married status did not independently predict lower CSM (HR: 0.85, p = 0.4). In females, 5-year CSM-FS rates were 88% for married versus 79% for unmarried patients (Δ = 9%). In multivariable CRMs, married status independently predicted lower CSM (HR: 0.58, p = 0.03). CONCLUSIONS: In nonmetastatic pelvic liposarcoma patients, married status independently predicted lower CSM only in female patients. In consequence, unmarried female patients should ideally require more assistance and more frequent follow-up than their married counterparts.

Office-based management of Non-Muscle Invasive Bladder Cancer (NMIBC): A position paper on current state of the art and future perspectives.

To the Editor, Bladder cancer is one of the most common cancers in humans, representing the 7th and 17th type of neoplasm in both genders. Its incidence and mortality are quite heterogeneous in different countries and are due to different risk factors, quality and prevalence of healthcare and the possibility of early diagnosis and treatment of the tumor and its potential recurrences [...].

Cancer-specific mortality in non-metastatic T1a renal cell carcinoma treated with radiotherapy versus partial nephrectomy.

PURPOSE: Radiotherapy (RT) represents a treatment option for small renal masses with proven feasibility and tolerability. However, it has never been directly compared to partial nephrectomy (PN) with cancer-specific mortality (CSM) as an endpoint. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified T1aN0M0 renal cell carcinoma (RCC) patients treated with RT or PN. We relied on 1:1 propensity score matching (PSM) for age, tumor size and histology. Subsequently, cumulative incidence plots and multivariable competing risks regression (CRR) models were fitted. The same methodology was then re-applied to a subset of patients with tumor size 21-40 mm. RESULTS: Of 40,355 patients with T1aN0M0 RCC, 40,262 underwent PN (99.8%) vs 93 underwent RT (0.2%). RT patients were older (median age 72 vs 60 years, p < 0.001) and harbored larger tumor size (median size 28 vs 25 mm, p < 0.001) and a higher proportion of non-clear cell RCC (49% vs 22%, p < 0.001). After 1:1 PSM (92 RT versus 92 PN patients), cumulative incidence plots' derived CSM was 21.3 vs 4%, respectively. In multivariable CRR models, RT independently predicted higher CSM (hazard ratio (HR) 4.3, p < 0.001). In the subgroup with tumor size 21-40 mm, after 1:1 PSM (72 RT versus 72 PN patients), cumulative incidence plots derived CSM was 21.3% vs 4%, respectively. In multivariable CRR models, RT also independently predicted higher CSM (HR 4.7, p = 0.001). CONCLUSIONS: In T1aN0M0 RCC patients, relative to PN, RT is associated with significantly higher absolute and relative CSM, even in patients with tumor size 21-40 mm.

Other-cause mortality in incidental prostate cancer.

BACKGROUND: In incidental prostate cancer (IPCa), elevated other-cause mortality (OCM) may obviate the need for active treatment. We tested OCM rates in IPCa according to treatment type and cancer grade and we hypothesized that OCM is significantly higher in not-actively-treated patients. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2015), IPCa patients were identified. Smoothed cumulative incidence plots as well as multivariable competing risks regression models were fitted to address OCM after adjustment for cancer-specific mortality (CSM). RESULTS: Of 5121 IPCa patients, 3655 (71%) were not-actively-treated while 1466 (29%) were actively-treated. Incidental PCa not-actively-treated patients were older and exhibited higher proportion of Gleason sum (GS) 6 and clinical T1a stage. In smoothed cumulative incidence plots, 5-year OCM was 20% for not-actively-treated versus 8% for actively-treated patients. Conversely, 5-year CSM was 5% for not-actively-treated versus 4% for actively-treated patients. No active treatment was associated with 1.4-fold higher OCM, even after adjustment for age, cancer characteristics, and CSM. According to GS, OCM reached 16%, 27%, and 35% in GS 6, 7, and 8-10 not-actively-treated IPCa patients, respectively and exceeded CSM recorded for the same three groups (2%, 6%, and 28%, respectively). CONCLUSION: Our results quantified OCM rates, confirming that in not-actively-treated IPCa patients OCM is indeed significantly higher than in their actively-treated counterparts (HR: 1.4). These observations validate the use of no active treatment in IPCa patients, in whom OCM greatly surpasses CSM (20% vs. 5%).

Perioperative Complications and In-Hospital Mortality in Partial and Radical Nephrectomy Patients with Heart-Valve Replacement.

BACKGROUND: In-hospital mortality and complication rates after partial and radical nephrectomy in patients with history of heart-valve replacement are unknown. PATIENTS AND METHODS: Relying on the National Inpatient Sample (2000-2019), kidney cancer patients undergoing partial or radical nephrectomy were stratified according to presence or absence of heart-valve replacement. Multivariable logistic and Poisson regression models addressed adverse hospital outcomes. RESULTS: Overall, 39,673 patients underwent partial nephrectomy versus 94,890 radical nephrectomy. Of those, 248 (0.6%) and 676 (0.7%) had a history of heart-valve replacement. Heart-valve replacement patients were older (median partial nephrectomy 69 versus 60 years; radical nephrectomy 71 versus 63 years), and more frequently exhibited Charlson comorbidity index ≥ 3 (partial nephrectomy 22 versus 12%; radical nephrectomy 32 versus 23%). In partial nephrectomy patients, history of heart-valve replacement increased the risk of cardiac complications [odds ratio (OR) 4.33; p < 0.001), blood transfusions (OR 2.00; p < 0.001), intraoperative complications (OR 1.53; p = 0.03), and longer hospital stay [rate ratio (RR) 1.25; p < 0.001], but not in-hospital mortality (p = 0.5). In radical nephrectomy patients, history of heart-valve replacement increased risk of postoperative bleeding (OR 4.13; p < 0.001), cardiac complications (OR 2.72; p < 0.001), intraoperative complications (OR 1.53; p < 0.001), blood transfusions (OR 1.27; p = 0.02), and longer hospital stay (RR 1.12; p < 0.001), but not in-hospital mortality (p = 0.5). CONCLUSIONS: History of heart-valve replacement independently predicted four of twelve adverse outcomes in partial nephrectomy and five of twelve adverse outcomes in radical nephrectomy patients including intraoperative and cardiac complications, blood transfusions, and longer hospital stay. Conversely, no statistically significant differences were observed in in-hospital mortality.

Can we predict pathology without surgery? Weighing the added value of multiparametric MRI and whole prostate radiomics in integrative machine learning models.

OBJECTIVE: To test the ability of high-performance machine learning (ML) models employing clinical, radiological, and radiomic variables to improve non-invasive prediction of the pathological status of prostate cancer (PCa) in a large, single-institution cohort. METHODS: Patients who underwent multiparametric MRI and prostatectomy in our institution in 2015-2018 were considered; a total of 949 patients were included. Gradient-boosted decision tree models were separately trained using clinical features alone and in combination with radiological reporting and/or prostate radiomic features to predict pathological T, pathological N, ISUP score, and their change from preclinical assessment. Model behavior was analyzed in terms of performance, feature importance, Shapley additive explanation (SHAP) values, and mean absolute error (MAE). The best model was compared against a naïve model mimicking clinical workflow. RESULTS: The model including all variables was the best performing (AUC values ranging from 0.73 to 0.96 for the six endpoints). Radiomic features brought a small yet measurable boost in performance, with the SHAP values indicating that their contribution can be critical to successful prediction of endpoints for individual patients. MAEs were lower for low-risk patients, suggesting that the models find them easier to classify. The best model outperformed (p ≤ 0.0001) clinical baseline, resulting in significantly fewer false negative predictions and overall was less prone to under-staging. CONCLUSIONS: Our results highlight the potential benefit of integrative ML models for pathological status prediction in PCa. Additional studies regarding clinical integration of such models can provide valuable information for personalizing therapy offering a tool to improve non-invasive prediction of pathological status. CLINICAL RELEVANCE STATEMENT: The best machine learning model was less prone to under-staging of the disease. The improved accuracy of our pathological prediction models could constitute an asset to the clinical workflow by providing clinicians with accurate pathological predictions prior to treatment. KEY POINTS: • Currently, the most common strategies for pre-surgical stratification of prostate cancer (PCa) patients have shown to have suboptimal performances. • The addition of radiological features to the clinical features gave a considerable boost in model performance. Our best model outperforms the naïve model, avoiding under-staging and resulting in a critical advantage in the clinic. •Machine learning models incorporating clinical, radiological, and radiomics features significantly improved accuracy of pathological prediction in prostate cancer, possibly constituting an asset to the clinical workflow.

The effect of race/ethnicity on cancer-specific mortality after trimodal therapy.

INTRODUCTION: Trimodal therapy (TMT) is the most validated bladder-sparing treatment for organ-confined urothelial carcinoma of the urinary bladder (OC UCUB, namely cT2N0M0). However, it is unknown if barriers to the use of TMT or cancer-specific mortality (CSM) differences exist according to race/ethnicity. We addressed this knowledge gap. MATERIAL AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified OC UCUB patients aged from 18 to 85 treated with radical cystectomy (RC) or TMT. Temporal trends described TMT versus RC use over time. Subsequently, in the subgroup of TMT-treated patients, survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM according to race/ethnicity. RESULTS: Among 19,501 assessable patients, 15,336 (79%) underwent RC versus 4165 TMT (21%). Overall, of all races/ethnicities, 16,245 (83.3%) were White Americans, 1215 (6.3%) Hispanics, 1160 (5.9%) African Americans, and 881 (4.5%) Asian/Pacific Islanders. Among TMT-treated patients, 3460 (83.1%) were White Americans, 298 (7.1%) African Americans, 218 (5.3%) Hispanics, and 189 (4.5%) Asian/Pacific Islanders. The lowest rate of TMT use relative to RC and TMT patients was recorded in Hispanics (17.9%). Over time, TMT use increased in White Americans (EAPC: + 4.5%, p = 0.001) and Asians/Pacific Islanders (EAPC: + 5.2%, p = 0.003), but not in others. Kaplan-Meier analyses showed median CSM of 49 months, 41 months, and 34 months and not reached in White Americans, Hispanics, African Americans, and Asian/Pacific Islanders, respectively (p = 0.02). In MCR models, two race/ethnicity subgroups independently predicted either worse (African Americans, HR: 1.20, p = 0.02) or better CSM (Asian/Pacific Islanders, HR: 0.75, p = 0.02). CONCLUSION: Race/ethnicity affects both access to TMT (lower access in Hispanics) as well as survival after TMT (better in Asians/Pacific Islanders and worse in African Americans).

Trimodal therapy effect on survival in urothelial vs non-urothelial bladder cancer.

OBJECTIVE: To address cancer-specific mortality free-survival (CSM-FS) differences in patients with urothelial carcinoma of the urinary bladder (UCUB) vs non-UCUB who underwent trimodal therapy (TMT), according to organ confined (OC: T2N0M0) vs non-organ confined (NOC: T3-4NanyM0 or TanyN1-3M0) clinical stages. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with cT2-T4N0-N3M0 bladder cancer treated with TMT, defined as the combination of transurethral resection of bladder tumour, chemotherapy, and radiotherapy. Temporal trends described TMT use over time. Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM in UCUB vs non-UCUB according to OC vs NOC stages. RESULTS: Of 5130 assessable TMT-treated patients, 425 (8%) harboured non-UCUB vs 4705 (92%) who had UCUB. The TMT rates increased for patients with OC UCUB from 92.4% to 96.8% (estimated annual percentage change of 0.4%, P < 0.001), but not in the NOC stages (P = 0.3). In the OC stage, the median CSM-FS was 36 months in patients with non-UCUB vs 60 months in those with UCUB, respectively (P = 0.01). Conversely, in the NOC stage, the median CSM-FS was 23 months both in UCUB and non-UCUB (P = 0.9). In the MCR models addressing OC stage, non-UCUB histology independently predicted higher CSM (hazard ratio 1.45, P = 0.004), but not in the NOC stage (P = 0.9). CONCLUSION: In OC UCUB, TMT rates have increased over time in a guideline-consistent fashion. Patients with OC non-UCUB treated with TMT showed a CSM disadvantage relative to OC UCUB. In the NOC stage, use of TMT resulted in dismal CSM, regardless of UCUB vs non-UCUB histology.

Identifying low cancer-specific mortality risk lymph node-positive radical prostatectomy patients.

OBJECTIVES: To identify low cancer-specific mortality (CSM) risk lymph node-positive (pN1) radical prostatectomy (RP) patients. METHODS: Within Surveillance, Epidemiology and End Results database (2010-2015) pN1 RP patients were identified. Kaplan-Meier plots and multivariable Cox-regression (MCR) models were used. Pathological characteristics were used to identify patients at lowest CSM risk. RESULTS: Overall, 2197 pN1 RP patients were identified. Overall, 5-year cancer-specific survival (CSS) rate was 93.3%. In MCR models ISUP GG1-2 (hazard ratio [HR]: 0.12, p < 0.001), GG3 (HR: 0.14, p < 0.001), GG4 (HR: 0.35, p = 0.002), pT2 (HR: 0.27, p = 0.012), pT3a (HR: 0.28, p = 0.003), pT3b (HR: 0.39, p = 0.009), and 1-2 positive lymph nodes (HR: 0.64, p = 0.04) independently predicted lower CSM. Pathological characteristics subgroups with the most protective hazard ratios were used to identify low-risk (ISUP GG1-3 and pT2-3a and 1-2 positive lymph nodes) patients versus others (ISUP GG4-5 or pT3b-4 or ≥3 positive lymph nodes). In Kaplan-Meier analyses, 5-year CSS rates were 99.3% for low-risk (n = 480, 21.8%) versus 91.8% (p < 0.001) for others (n = 1717, 78.2%). CONCLUSIONS: Lymph node-positive RP patients exhibit variable CSS rates. Within this heterogeneous group, those at very low risk of CSM may be identified based on pathological characteristics, namely ISUP GG1-3, pT2-3a, and 1-2 positive lymph nodes. Such stratification scheme might be of value for individual patients counseling, as well as in design of clinical trials.