Radiotherapy Versus Partial Penectomy for T1 Squamous Cell Carcinoma of the Penis.

BACKGROUND: Radiotherapy (RT) represents an alternative treatment option for patients with T1 squamous cell carcinoma of the penis (SCCP), with proven feasibility and tolerability. However, it has never been directly compared with partial penectomy (PP) using cancer-specific mortality (CSM) as an end point. METHODS: In the Surveillance, Epidemiology, and End Results database (2000-2020), T1N0M0 SCCP patients treated with RT or PP were identified. This study relied on 1:4 propensity score-matching (PSM) for age at diagnosis, tumor stage, and tumor grade. Subsequently, cumulative incidence plots as well as multivariable competing risks regression (CRR) models addressed CSM. Additionally, the study accounted for the confounding effect of other-cause mortality (OCM). RESULTS: Of 895 patients with T1N0M0 SCCP, 55 (6.1%) underwent RT and 840 (93.9%) underwent PP. The RT and PP patients had a similar age distribution (median age, 70 vs 70 years) and more frequently harbored grade I or II tumors (67.3% vs 75.8%) as well as T1a-stage disease (67.3% vs 74.3%). After 1:4 PSM, 55 (100%) of the 55 RT patients versus 220 (26.2%) of the 840 PP patients were included in the study. The 10-year CSM derived from the cumulative incidence plots was 25.4% for RT and 14.4% for PP. In the multivariable CRR models, RT independently predicted a higher CSM than PP (hazard ratio, 1.99; 95% confidence interval, 1.05-3.80; p = 0.04). CONCLUSION: For the T1N0M0 SCCP patients treated in the community, RT was associated with nearly a twofold higher CSM than PP. Ideally, a validation study based on tertiary care institution data should be conducted to test whether this CSM disadvantage is operational only in the community or not.

Evaluation of margins during radical prostatectomy: confocal microscopy vs frozen section analysis.

OBJECTIVES: To test the performance of ex vivo fluorescence confocal microscopy (FCM; Vivascope 2500M-G4), as compared to intra-operative frozen section (IFS) analysis, to evaluate surgical margins during robot-assisted radical prostatectomy (RARP), with final pathology as the reference standard. METHODS: Overall, 54 margins in 45 patients treated with RARP were analysed with: (1) ex vivo FCM; (2) IFS analysis; and (3) final pathology. FCM margins were evaluated by two different pathologists (experienced [M.I.: 10 years] vs highly experienced [G.R.: >30 years]) as strongly negative, probably negative, doubtful, probably positive, or strongly positive. First, inter-observer agreement (Cohen's κ) between pathologists was tested. Second, we reported the sensitivity, specificity, positive predictive (PPV) and negative predictive value (NPV) of ex vivo FCM. Finally, agreement between ex vivo FCM and IFS analysis (Cohen's κ) was reported. For all analyses, four combinations of FCM results were evaluated. RESULTS: At ex vivo FCM, the inter-observer agreement between pathologists ranged from moderate (κ = 0.74) to almost perfect (κ = 0.90), according to the four categories of results. Indeed, at ex vivo FCM, the highly experienced pathologist reached the best balance between sensitivity (70.5%) specificity (91.8%), PPV (80.0%) and NPV (87.1%). Conversely, on IFS analysis, the sensitivity, specificity, PPV and NPV were, respectively, 88.2% vs 100% vs 100% vs 94.8%. The agreement between the ex vivo FCM and IFS analyses ranged from moderate (κ = 0.62) to strong (κ = 0.86), according to the four categories of results. CONCLUSION: Evaluation of prostate margins at ex vivo FCM appears to be feasible and reliable. The agreement between readers encourages its widespread use in daily practice. Nevertheless, as of today, the performance of FCM seems to be sub-par when compared to the established standard of care (IFS analysis).

Microwave vs radiofrequency ablation for small renal masses: perioperative and oncological outcomes.

OBJECTIVE: To conduct a comprehensive comparison of microwave ablation (MWA) vs radiofrequency ablation (RFA) outcomes in the treatment of small renal masses (SRMs), specifically: TRIFECTA ([i] complete ablation, [ii] absence of Clavien-Dindo Grade ≥III complications, and [iii] absence of ≥30% decrease in estimated glomerular filtration rate) achievement, operative time (OT), and local recurrence rate (LRR). PATIENTS AND METHODS: We retrospectively analysed 531 patients with SRMs (clinical T1a-b) treated with MWA or RFA at a single centre (2008-2022). First, multivariable logistic regression models were used for testing TRIFECTA achievement. Second, multivariable Poisson regression models were used to evaluate variables associated with longer OT. Finally, Kaplan-Meier plots depicted LRR over time. All analyses were repeated after 1:1 propensity score matching (PSM). RESULTS: Of 531 patients with SRMs, 373/531 (70.2%) underwent MWA and 158/531 (29.8%) RFA. MWA demonstrated superior TRIFECTA achievement (314/373 [84.2%]) compared to RFA (114/158 [72.2%], P = 0.001). These differences were driven by higher rates of complete ablation in MWA- vs RFA-treated patients (348/373 [93.3%] vs 137/158 [86.7%], P < 0.001). In multivariable logistic regression models, MWA was associated with higher TRIFECTA achievement, compared to RFA, before (odds ratio [OR] 1.92, P = 0.008) and after PSM (OR 1.99, P = 0.023). Finally, the median OT was shorter for MWA vs RFA (105 vs 115 min; P = 0.002). At Poisson regression analyses, MWA predicted shorter OT before (incidence rate ratio [IRR] 0.86, P < 0.001) and after PSM (IRR 0.85, P < 0.001). Local recurrence occurred in 17/373 (4.6%) MWA-treated patients and 21/158 (13.3%) RFA-treated patients (P = 0.29) after a median (interquartile range) follow-up of 24 (8-46) months. There were no differences in the LRR in Kaplan-Meier plots before (P = 0.29) and after PSM (P = 0.42). CONCLUSION: Microwave ablation provides higher TRIFECTA achievement, and shorter OT than RFA. No significant differences were found regarding the LRR.

Effect of race/ethnicity on survival in surgically treated intermediate/high risk non-metastatic clear cell renal carcinoma.

PURPOSE: It is unknown to what extent 10-year overall survival of radical nephrectomy treated intermediate/high-risk non-metastatic clear cell renal carcinoma patients differs from age- and sex-matched population-based controls, especially when race/ethnicity is considered (Caucasian vs. African American vs. Hispanic vs. Asian/Pacific Islander). METHODS: We relied on the SEER database (2004-2018) to identify newly diagnosed radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients. For each case, we simulated an age- and sex-matched control relying on Social Security Administration Life Tables with 10 years of follow-up. We compared overall survival between renal carcinoma cases and population-based controls. Multivariable competing risks regression models tested for predictors of cancer-specific mortality versus other-cause mortality. RESULTS: Of 6877 radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients, 5050 (73%) were Caucasian versus 433 (6%) African American versus 1002 (15%) Hispanic versus 392 (6%) Asian/Pacific Islanders. At 10 years, overall survival difference between radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients versus population-based controls was greatest in African Americans (51% vs. 81%, Δ = 30%), followed by Hispanics (54% vs. 80%, Δ = 26%), Asian/Pacific Islanders (56% vs. 80%, Δ = 24%) and Caucasians (52% vs. 74%, Δ = 22%). In competing risks regression, only African Americans exhibited significantly higher other cause mortality (hazard ratio = 1.3; 95% confidence interval = 1.1 - 1.6; p = 0.01) than others. CONCLUSION: Relative to Life Tables' derived sex- and age-matched controls, radical nephrectomy treated intermediate/high-risk non-metastatic clear cell renal carcinoma patients exhibit worse overall survival, with worst overall survival recorded in African Americans of all race/ethnicity groups.

Association between mpMRI detected tumor apparent diffusion coefficient and 5-year biochemical recurrence risk after radical prostatectomy.

PURPOSE: To assess the ability of tumor apparent diffusion coefficient (ADC) values obtained from multiparametric magnetic resonance imaging (mpMRI) to predict the risk of 5-year biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: This retrospective analysis included 1207 peripheral and 232 non-peripheral zone prostate cancer (PCa) patients who underwent mpMRI before RP (2012-2015), with the outcome of interest being 5-year BCR. ADC was evaluated as a continuous variable and as categories: low (< 850 µm2/s), intermediate (850-1100 µm2/s), and high (> 1100 µm2/s). Kaplan-Meier curves with log-rank testing of BCR-free survival, multivariable Cox proportional hazard regression models were formed to estimate the risk of BCR. RESULTS: Among the 1439 males with median age 63 (± 7) years, the median follow-up was 59 months, and 306 (25%) patients experienced BCR. Peripheral zone PCa patients with BCR had lower tumor ADC values than those without BCR (874 versus 1025 µm2/s, p < 0.001). Five-year BCR-free survival rates were 52.3%, 74.4%, and 87% for patients in the low, intermediate, and high ADC value categories, respectively (p < 0.0001). Lower ADC was associated with BCR, both as continuously coded variable (HR: 5.35; p < 0.001) and as ADC categories (intermediate versus high ADC-HR: 1.56, p = 0.017; low vs. high ADC-HR; 2.36, p < 0.001). In the non-peripheral zone PCa patients, no association between ADC and BCR was observed. CONCLUSION: Tumor ADC values and categories were found to be predictive of the 5-year BCR risk after RP in patients with peripheral zone PCa and may serve as a prognostic biomarker.

Multiparametric MRI-based 5-year Risk Prediction Model for Biochemical Recurrence of Prostate Cancer after Radical Prostatectomy.

Background Current predictive tools to estimate the risk of biochemical recurrence (BCR) after treatment of prostate cancer do not consider multiparametric MRI (mpMRI) information. Purpose To develop a risk prediction tool that considers mpMRI findings to assess the risk of 5-year BCR after radical prostatectomy. Materials and Methods In this retrospective single-center analysis in 1459 patients with prostate cancer who underwent mpMRI before radical prostatectomy (in 2012-2015), the outcome of interest was 5-year BCR (two consecutive prostate-specific antigen [PSA] levels > 0.2 ng/mL [0.2 µg/L]). Patients were randomly divided into training (70%) and test (30%) sets. Kaplan-Meier plots were applied to the training set to estimate survival probabilities. Multivariable Cox regression models were used to test the relationship between BCR and different sets of exploratory variables. The C-index of the final model was calculated for the training and test sets and was compared with European Association of Urology, University of California San Francisco Cancer of the Prostate Risk Assessment, Memorial Sloan-Kettering Cancer Center, and Partin risk tools using the partial likelihood ratio test. Five risk categories were created. Results The median duration of follow-up in the whole cohort was 59 months (IQR, 32-81 months); 376 of 1459 (25.8%) patients had BCR. A multivariable Cox regression model (referred to as PIPEN, and composed of PSA density, International Society of Urological Pathology grade group, Prostate Imaging Reporting and Data System category, European Society of Urogenital Radiology extraprostatic extension score, nodes) fitted to the training data yielded a C-index of 0.74, superior to that of other predictive tools (C-index 0.70 for all models; P ≤ .01) and a median higher C-index on 500 test set replications (C-index, 0.73). Five PIPEN risk categories were identified with 5-year BCR-free survival rates of 92%, 84%, 71%, 56%, and 26% in very low-, low-, intermediate-, high-, and very high-risk patients, respectively (all P < .001). Conclusion A five-item model for predicting the risk of 5-year BCR after radical prostatectomy for prostate cancer was developed and internally verified, and five risk categories were identified. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Aguirre and Ortegón in this issue.

Repeat MRI during active surveillance: natural history of prostatic lesions and upgrading rates.

OBJECTIVES: To assess upgrading rates in patients on active surveillance (AS) for prostate cancer (PCa) after serial multiparametric magnetic resonance imaging (mpMRI). METHODS: We conducted a retrospective analysis of 558 patients. Five different criteria for mpMRI progression were used: 1) a Prostate Imaging Reporting and Data System (PI-RADS) score increase; 2) a lesion size increase; 3) an extraprostatic extension score increase; 4) overall mpMRI progression; and 5) the number of criteria met for mpMRI progression (0 vs 1 vs 2-3). In addition, two definitions of PCa upgrading were evaluated: 1) International Society of Urological Pathology Grade Group (ISUP GG) ≥2 with >10% of pattern 4 and 2) ISUP GG ≥ 3. Estimated annual percent changes methodology was used to show the temporal trends of mpMRI progression criteria. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of mpMRI progression criteria were also analysed. Multivariable logistic regression models tested PCa upgrading rates. RESULTS: Lower rates over time for all mpMRI progression criteria were observed. The NPV of serial mpMRI scans ranged from 90.5% to 93.5% (ISUP GG≥2 with >10% of pattern 4 PCa upgrading) and from 98% to 99% (ISUP GG≥3 PCa upgrading), depending on the criteria used for mpMRI progression. A prostate-specific antigen density (PSAD) threshold of 0.15 ng/mL/mL was used to substratify those patients who would be able to skip a prostate biopsy. In multivariable logistic regression models assessing PCa upgrading rates, all five mpMRI progression criteria achieved independent predictor status. CONCLUSION: During AS, approximately 27% of patients experience mpMRI progression at first repeat MRI. However, the rates of mpMRI progression decrease over time at subsequent mpMRI scans. Patients with stable mpMRI findings and with PSAD < 0.15 ng/mL/mL could safely skip surveillance biopsies. Conversely, patients who experience mpMRI progression should undergo a prostate biopsy.

Association between previous negative biopsies and lower rates of progression during active surveillance for prostate cancer.

PURPOSE: To test any-cause discontinuation and ISUP GG upgrading rates during Active Surveillance (AS) in patients that underwent previous negative biopsies (PNBs) before prostate cancer (PCa) diagnosis vs. biopsy naive patients. METHODS: Retrospective analysis of 961 AS patients (2008-2020). Three definitions of PNBs were used: (1) PNBs status (biopsy naïve vs. PNBs); (2) number of PNBs (0 vs. 1 vs. ≥ 2); (3) histology at last PNB (no vs. negative vs. HGPIN/ASAP). Kaplan-Meier plots and multivariable Cox models tested any-cause and ISUP GG upgrading discontinuation rates. RESULTS: Overall, 760 (79.1%) vs. 201 (20.9%) patients were biopsy naïve vs. PNBs. Specifically, 760 (79.1%) vs. 138 (14.4%) vs. 63 (6.5%) patients had 0 vs. 1 vs. ≥ 2 PNBs. Last, 760 (79.1%) vs. 134 (13.9%) vs. 67 (7%) patients had no vs. negative PNB vs. HGPIN/ASAP. PNBs were not associated with any-cause discontinuation rates. Conversely, PNBs were associated with lower rates of ISUP GG upgrading: (1) PNBs vs. biopsy naïve (HR:0.6, p = 0.04); (2) 1 vs. 0 PNBs (HR:0.6, p = 0.1) and 2 vs. 0 PNBs, (HR:0.5, p = 0.1); (3) negative PNB vs. biopsy naïve (HR:0.7, p = 0.3) and HGPIN/ASAP vs. biopsy naïve (HR:0.4, p = 0.04). However, last PNB ≤ 18 months (HR:0.4, p = 0.02), but not last PNB > 18 months (HR:0.8, p = 0.5) were associated with lower rates of ISUP GG upgrading. CONCLUSION: PNBs status is associated with lower rates of ISUP GG upgrading during AS for PCa. The number of PNBs and time from last PNB to PCa diagnosis (≤ 18 months) appear also to be critical for patient selection.

Active surveillance for prostate cancer: comparison between incidental tumors vs. tumors diagnosed at prostate biopsies.

PURPOSE: To test discontinuation rates during Active Surveillance (AS) in patients diagnosed with incidental prostate cancers (IPCa) vs. tumors diagnosed at prostate biopsies (BxPCa). METHODS: Retrospective single center analysis of 961 vs. 121 BxPCa vs. IPCa patients (2008-2020). Kaplan-Meier plots and multivariable Cox regression models tested four different outcomes: (1) any-cause discontinuation; (2) discontinuation due to ISUP GG upgrading; (3) biopsy discontinuation due to ISUP GG upgrading or > 3 positive cores; (4) biopsy discontinuation or suspicious extraprostatic extension at surveillance mpMRI. Then, multivariable logistic regression models tested rates of clinically significant PCa (csPCa) (ISUP GG ≥ 3 or pT ≥ 3a or pN1) after radical prostatectomy (RP). RESULTS: Median time follow-up was 35 (19-64) months. IPCa patients were at lower risk of any-cause (3-year survival: 79.3 vs. 66%; HR: 0.5, p = 0.001) and biopsy/MRI AS discontinuation (3-year survival: 82.3 vs. 72.7%; HR: 0.5, p = 0.001), compared to BxPCa patients. Conversely, IPCa patients exhibited same rates of biopsy discontinuation and ISUP GG upgrading over time, relative to BxPCa. In multivariable logistic regression models, IPCa patients were associated with higher rates of csPCa at RP (OR: 1.4, p = 0.03), relative to their BxPCa counterparts. CONCLUSION: AS represents a safe management strategy for IPCa. Compared to BxPCa, IPCa patients are less prone to experience any-cause and biopsy/MRI AS discontinuation. However, the two mentioned groups present similar rates of biopsy discontinuation and ISUP GG upgrading over time. In consequence, tailored AS protocols with scheduled repeated surveillance biopsies should be offered to all newly diagnosed IPCa patients.

Adjuvant radiotherapy in node positive prostate cancer patients: a debate still on. when, for whom?

OBJECTIVE: To evaluate the impact of adjuvant radiotherapy (aRT) in patients with prostate cancer (PCa) found to have pathological positive lymph nodes (pN1s) after radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) with regard to distant recurrence-free survival (RFS), according to both main tumour pathological characteristics and number of positive lymph nodes. Biochemical RFS, local RFS, overall survival (OS) and acute and late toxicity were assessed as secondary endpoints. PATIENTS AND METHODS: A retrospective cohort of 187 consecutive patients with pN1 PCa were treated with aRT at the IEO, European Institute of Oncology IRCCS, Milan, Italy. aRT on the tumour bed and pelvis was administered within 6 months of RP. Androgen deprivation therapy was administered according to the guidelines. Univariate and multivariate Cox regression analyses predicting biochemical RFS, local RFS, distant RFS and OS rates were performed to assess whether the number of pN1s represented an independent prognostic factor. The Youden index was computed to find the optimal threshold for the number of pN1s able to discriminate between patients with or without biochemical and clinical relapse. RESULTS: At 5 years, local RFS, distant RFS, biochemical RFS and OS were 68%, 71%, 56% and 94%, respectively. The median follow-up was 49 months. The number of pN1s was significantly associated with biochemical RFS, local RFS and distant RFS. The best threshold for discriminating between patients with or without biochemical and clinical relapse was five pN1s. In multivariate analyses, the number of pN1s was confirmed to be an independent predictor of biochemical RFS, local RFS and distant RFS, but not of OS. Multivariate analyses also showed an increased risk of biochemical relapse for increasing values of initial prostate-specific antigen and for patients with tumour vascular invasion. Local and distant RFS were also inversely correlated with significantly reduced risk for International Society of Urological Pathology grade group <3 (group 1 or 2 compared to group 3). CONCLUSIONS: Our data confirmed the encouraging outcomes of patients with pN1 PCa treated with adjuvant treatments and the key role represented by the number of pN1s in predicting biochemical RFS, clinical RFS and distant RFS. Large prospective cohort studies and randomized clinical trials are needed to confirm these results and to identify the subgroup of patients with pN1 PCa who would most benefit from aRT.

Uro-oncologic patient management during the COVID-19 pandemic: survey findings from an Italian oncologic hub.

Aim: Patient and worker satisfaction at an oncologic hub during the COVID-19 pandemic has never been reported. We addressed this topic. Methods: We conducted a survey to test the views of patients (n = 64) and healthcare professionals (n = 52) involved with our operative protocol. Results: A moderate/severe grade of concern due to the COVID-19 emergency was recorded in 63% of patients versus 75% of hospital staff. High/very high versus low satisfaction grade about preventive strategies to reduce the risk of SARS-CoV-2 contagion was identified in the patients compared with the hospital staff group. Conclusion: Surgical treatment at a hub center of uro-oncologic patients coming from spoke centers is well accepted and should, therefore, be recommended. Preventive strategies to reduce the risk of SARS-CoV-2 contagion in hospital staff members should be implemented.

Lay abstract We provide robust evidence that an oncologic hub center during COVID-19 pandemic represents a credible solution for management of non-deferrable uro-oncologic patients. Specifically, surgical treatment at a hub center of patients coming from spoke centers is well accepted by both patients and hospital staff members. Moreover, collaboration between healthcare workers from spoke and hub centers generates minimal levels of anxiety, while potentially being associated with clinical, surgical and scientific improvement. This said, a more specific focus on recommended strategies to reduce the risk of SARS-CoV-2 contagion at oncologic hub hospitals is warranted.

A novel nomogram to identify candidates for active surveillance amongst patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 or ISUP GG2 prostate cancer, according to multiparametric magnetic resonance imaging findings.

OBJECTIVES: To develop a novel nomogram to identify candidates for active surveillance (AS) that combines clinical, biopsy and multiparametric magnetic resonance imaging (mpMRI) findings; and to compare its predictive accuracy to, respectively: (i) Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, (ii) Johns Hopkins (JH) criteria, (iii) European Association of Urology (EAU) low-risk classification, and (iv) EAU low-risk or low-volume with International Society of Urological Pathology (ISUP) Grade Group (GG) 2 classification. PATIENTS AND METHODS: We selected 1837 patients with ISUP GG1 or GG2 prostate cancer (PCa), treated with radical prostatectomy (RP) between 2012 and 2018. The outcome of interest was the presence of unfavourable disease (i.e., clinically significant PCa [csPCa]) at RP, defined as: ISUP GG ≥ 3 and/or pathological T stage (pT) ≥3a and/or pathological N stage (pN) 1. First, logistic regression models including PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 binary classifications (not eligible vs eligible) were used. Second, a multivariable logistic regression model including age, prostate-specific antigen density (PSA-D), ISUP GG, and the percentage of positive cores (Model 1) was fitted. Third, Prostate Imaging-Reporting and Data System (PI-RADS) score (Model 2), extracapsular extension (ECE) score (Model 3) and PI-RADS + ECE score (Model 4) were added to Model 1. Only variables associated with higher csPCa rates in Model 4 were retained in the final simplified Model 5. The area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses were used. RESULTS: Of the 1837 patients, 775 (42.2%) had csPCa at RP. Overall, 837 (47.5%), 986 (53.7%), 348 (18.9%), and 209 (11.4%) patients were eligible for AS according to, respectively, the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS, and JH criteria. The proportion of csPCa amongst the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS and JH candidates was, respectively 28.5%, 29.3%, 25.6% and 17.2%. Model 4 and Model 5 (in which only PSA-D, ISUP GG, PI-RADS and ECE score were retained) had a greater AUC (0.84), compared to the four proposed AS criteria (all P < 0.001). The adoption of a 25% nomogram threshold increased the proportion of AS-eligible patients from 18.9% (PRIAS) and 11.4% (JH) to 44.4%. Moreover, the same 25% nomogram threshold resulted in significantly lower estimated risks of csPCa (11.3%), compared to PRIAS (Δ: -14.3%), JH (Δ: -5.9%), EAU low-risk (Δ: -17.2%), and EAU low-risk or low-volume ISUP GG2 classifications (Δ: -18.0%). CONCLUSION: The novel nomogram combining clinical, biopsy and mpMRI findings was able to increase by ~25% and 35% the absolute frequency of patients suitable for AS, compared to, respectively, the PRIAS or JH criteria. Moreover, this nomogram significantly reduced the estimated frequency of csPCa that would be recommended for AS compared to, respectively, the PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 classifications.

Conditional Survival of Patients With Nonmetastatic Renal Cell Carcinoma: How Cancer-Specific Mortality Changes After Nephrectomy.

BACKGROUND: Conditional survival (CS) may reveal important differences in cancer-specific mortality (CSM) among patients with nonmetastatic renal cell carcinoma (nmRCC). This study assessed CS according to T and N stages in patients treated surgically for nmRCC. PATIENTS AND METHODS: Within the SEER database (2001-2015), all patients with nmRCC treated with either partial or radical nephrectomy were identified. CSM-free estimates according to T and N stage and substage groupings (pT1aN0-pT4N0 and pTanyN1) and multivariable Cox regression models with adjustment for Fuhrman grade and histologic subtype were assessed. RESULTS: According to T and N stage and substage groupings, the following patients were included in the study: 35,966 (46.2%) with pT1aN0 disease; 18,858 (24.2%) with pT1bN0; 5,977 (7.7%) with pT2aN0; 2,511 (3.2%) with pT2bN0; 11,839 (15.2%) with pT3aN0; 1,037 (1.3%) with pT3b-cN0; 402 (0.5%) with pT4N0; and 1,302 (1.7%) with pTanyN1. Conditional CSM-free survival estimates were 98.2% at 1 year versus 98.0% at 10 years of event-free follow-up for patients with pT1aN0 disease, relative to baseline. Conversely, pT4N0/pTanyN1 conditional CSM-free survival estimates were 55.8% at 1 year versus 77.9% at 8 years of event-free follow-up. Attrition due to mortality was highest in patients with pT4N0/pTanyN1 disease. In multivariable Cox regression analyses, T stage, tumor grade, and histologic subtype represented independent predictors, but no interactions were identified. CONCLUSIONS: Tumor stage and its substages represent extremely important determinants of prognosis after lengthy event-free follow-up. The recorded observations have critical importance for physicians regarding patient follow-up and counseling.

Contemporary North-American population-based validation of the International Germ Cell Consensus Classification for metastatic germ cell tumors of the testis.

BACKGROUND: The International Germ Cell Consensus Classification (IGCCC) is the recommended stratification scheme for newly diagnosed metastatic seminoma (mSGCT) and non-seminoma germ cell tumor (mNSGCT) patients. However, a contemporary North-American population-based validation has never been completed and represented our focus. MATERIALS AND METHODS: We identified mSGCT and mNSGCT patients within the SEER database (2004-2015). The IGCCC criteria were used for stratification into prognostic groups. Kaplan-Meier (KM) derived actuarial 5-year overall survival (OS) rates were calculated. In addition, cumulative incidence plots tested cancer-specific (CSM) and other-cause mortality (OCM) rates. RESULTS: Of 321 mSGCT patients, 190 (59.2%) and 131 (40.8%), respectively, fulfilled good and intermediate prognosis criteria. Of 803 mNSGCT patients, 209 (26.1%), 100 (12.4%), and 494 (61.5%), respectively, fulfilled good, intermediate, and poor prognosis criteria. In mSGCT patients, actuarial KM derived 5-year OS was 87% and 78% for, respectively, good and intermediate prognosis groups (p = 0.02). In cumulative incidence analyses, statistically significant differences were recorded for CSM but not for OCM between good versus intermediate prognosis groups. In mNSGCT patients, actuarial KM derived 5-year OS was 89%, 75% and 60% for, respectively, good, intermediate, and poor prognosis groups (p < 0.001). In cumulative incidence analyses, statistically significant differences were recorded for both CSM and OCM between good, intermediate, and poor prognosis groups. CONCLUSIONS: Our findings represent the first population-based validation of the IGCCC in contemporary North-American mSGCT and mNSGCT patients. The recorded OM rates closely replicate those of the original publication, except for better survival of poor prognosis mNSGCT patients.

Contemporary conditional cancer-specific survival after radical nephroureterectomy in patients with nonmetastatic urothelial carcinoma of upper urinary tract.

BACKGROUND AND OBJECTIVES: To examine the effect of conditional survival on 5-year cancer-specific survival (CSS) probability after radical nephroureterectomy (RNU) in a contemporary cohort of patients with non-metastatic urothelial carcinoma of the upper urinary tract (UTUC). METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), 6826 patients were identified. Conditional 5-year CSS estimates were assessed after event-free follow-up duration. Multivariable Cox regression (MCR) models predicted cancer-specific mortality (CSM) according to event-free follow-up length. RESULTS: Overall, 956 (14.0%) were T1 low grade(LG)N0 , 1305 (19.1%) T1 high grade(HG)N0 , 1215 (17.8%) T2 N0 , 2249 (32.9%) T3 N0 and 1101 (16.1%) T4 N0 /Tany N1-3 . From baseline, 93.4% to 94.2% in T1 LGN0 provided 5-year CSS and, respectively, 86.2% to 95.3% in T1 HGN0 , 77.5% to 87.8% in T2 N0 , 63.0% to 91.1% in T3 N0 , and 38.8% to 88.2% in T4 N0 /Tany N1-3 . In MCR models, relative to T1 LGN0 , T1 HGN0 (Hazard ratio [HR] 1.7), T2 N0 (HR 3.0), T3 N0 (HR: 5.2), and T4 N0 /Tany N1-3 (HR 11.9) were independent predictors of higher CSM. Conditional HRs decreased to levels equivalent to T1 LGN0 at 3 years vs 5 years of event-free survival for T1 HGN0 and all other groups, respectively. CONCLUSIONS: A direct relationship exists between event-free follow-up and survival probability after RNU. From a clinical perspective, such survival estimates may have particular importance during preoperative counseling.

Adherence to guideline recommendations for multimodality treatment of patients with pT2-3 M0 non-urothelial carcinoma of the urinary bladder: Temporal trends and survival outcomes.

OBJECTIVES: To analyze contemporary multimodality treatment rates, defined as radical cystectomy plus chemotherapy and/or radiotherapy, for pT2-3 any N-stage M0 non-urothelial carcinoma of urinary bladder patients. Additionally, we tested for the effect of multimodality treatment versus radical cystectomy alone on cancer-specific mortality. METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), 887 pT2-3 any N-stage M0 non-urothelial carcinoma of urinary bladder patients treated with radical cystectomy were identified. Kaplan-Meier plots, and univariable and multivariable Cox regression analyses focused on cancer-specific mortality rates. RESULTS: Squamous cell carcinoma was recorded in 499 (56.3%) patients, neuroendocrine carcinoma in 246 (27.7%) and adenocarcinoma in 142 (16.0%). The highest proportion of multimodality treatment patients was recorded in neuroendocrine carcinoma (69.1%), relative to adenocarcinoma (34.5%) and squamous cell carcinoma (26.4%). A statistically significant annual increase was recorded in multimodality treatment rates in neuroendocrine carcinoma patients (46.7-74.2%, P < 0.01), but not in adenocarcinoma or squamous cell carcinoma patients. The 5-year cancer-specific mortality rate in neuroendocrine carcinoma patients was significantly lower after multimodality treatment versus radical cystectomy alone (37.0% vs 51.5%; P < 0.01), but no statistically significant differences were recorded in both adenocarcinoma (46.1% vs 35.5%; P = 0.8) and squamous cell carcinoma (41.4% vs 31.1%; P = 0.8) patients. In multivariable analyses, for neuroendocrine carcinoma patients, multimodality treatment was an independent predictor of a lower cancer-specific mortality rate (hazard ratio 0.58, P = 0.03). CONCLUSIONS: Multimodality treatment has been increasingly used during the study period in neuroendocrine carcinoma patients, and it has translated into a cancer-specific mortality benefit. This is not the case for other non-urothelial carcinoma of urinary bladder patients, such as adenocarcinoma or squamous cell carcinoma.

Cryoablation Predisposes to Higher Cancer Specific Mortality Relative to Partial Nephrectomy in Patients with Nonmetastatic pT1b Kidney Cancer.

PURPOSE: Cryoablation is done in select patients with pT1b nonmetastatic renal cell carcinoma without convincing proof of efficacy. Our aim was to test for differences in the cancer specific mortality rate for cryoablation and partial nephrectomy in T1b nonmetastatic renal cell carcinoma cases. MATERIALS AND METHODS: In the 2004 to 2015 SEER (Surveillance, Epidemiology, and End Results) database we identified 5,763 patients with a T1b tumor treated with cryoablation or partial nephrectomy. Modeling relied on multivariable logistic regression models predicting cryoablation vs partial nephrectomy. After 1:2 ratio propensity score matching between patients treated with cryoablation vs partial nephrectomy we used cumulative incidence plot and competing risks regression to test differences in cancer specific mortality and other cause mortality rates. RESULTS: Relative to the 5,521 patients who underwent partial nephrectomy the 242 treated with cryoablation were older, had smaller tumors and more frequently harbored unclassified renal cell carcinoma of low or unknown grade. Median followup was 38 months. In multivariable logistic regression models predicting cryoablation vs partial nephrectomy more advanced patient age was an independent predictor (OR 1.03; p=0.007). After propensity score matching and other cause mortality adjustment the 5-year cancer specific mortality rate was 2.5-fold higher after cryoablation than after partial nephrectomy (p=0.03). Conversely after propensity score matching and cancer specific mortality adjustment the 5-year other cause mortality rate was similar to that of partial nephrectomy after cryoablation (HR 1.45, p=0.12). The major limitation of this study was the lack of recurrence and metastatic progression data. CONCLUSIONS: The current findings demonstrated a 2.5-fold increase in cancer specific mortality when cryoablation was performed in patients with pT1b renal cell carcinoma. This observation should be interpreted as a contraindication to cryoablation outside clinical trials or institutional protocols.

Long-term incidence of secondary bladder and rectal cancer in patients treated with brachytherapy for localized prostate cancer: a large-scale population-based analysis.

OBJECTIVE: To examine the incidence and time trends of secondary bladder cancer (BCa) and rectal cancer (RCa) after brachytherapy (BT) relative to radical prostatectomy (RP). MATERIALS AND METHODS: Within the Surveillance, Epidemiology and End Results (SEER) database (1988-2015), we identified patients with localized PCa as an only or first primary cancer, who underwent BT or RP. Cumulative incidence plots and multivariable competing-risks regression (CRR) models were used. Sensitivity analyses focused on patients' age and year of diagnosis intervals and tested the effect of an unmeasured confounder. RESULTS: Of 318 058 patients with localized prostate cancer (PCa), 55 566 (18.4%) underwent BT. After propensity score-matching, 20-year secondary BCa incidence was 6.0% in patients who had undergone BT vs 2.4% in those who had undergone RP (P < 0.001) and the respective 20-year secondary RCa incidence was 1.1% vs 0.5% (P < 0.001). In multivariable CRR models, BT predicted higher secondary BCa (hazard ratio [HR] 1.58; P < 0.001) and RCa rates (HR 1.59; P < 0.001) vs RP. Sensitivity analyses replicated the same results after stratification according to age and showed HRs of decreasing magnitude for historical, intermediate and contemporary years of diagnosis. An unmeasured confounder with an HR of 2 would render the effect of BT statistically insignificant if it affected patients in the RP group with a ratio of 2 relative to those in the BT group. Finally, temporal trends showed a decrease of secondary 5-year BCa and RCa rates.> CONCLUSIONS: Brachytherapy predominantly increases the risk of secondary BCa and, to a lesser extent, that of RCa. Follow-up of such patients is therefore required. It is encouraging that both secondary BCa, and RCa rates, in particular, have recently decreased, RCa.

Trends and Social Barriers for Inpatient Palliative Care in Patients With Metastatic Bladder Cancer Receiving Critical Care Therapies.

BACKGROUND: Use of inpatient palliative care (IPC) in the treatment of advanced cancer represents a well-established guideline recommendation. A recent analysis showed that patients with genitourinary cancer benefit from IPC at the second lowest rate among 4 examined primary cancers, namely lung, breast, colorectal, and genitourinary. Based on this observation, temporal trends and predictors of IPC use were examined in patients with metastatic urothelial carcinoma of the bladder (mUCB) receiving critical care therapies (CCTs). PATIENTS AND METHODS: Patients with mUCB receiving CCTs were identified within the Nationwide Inpatient Sample database (2004-2015). IPC use rates were evaluated in estimated annual percentage change (EAPC) analyses. Multivariable logistic regression models with adjustment for clustering at the hospital level were used. RESULTS: Of 1,944 patients with mUCB receiving CCTs, 191 (9.8%) received IPC. From 2004 through 2015, IPC use increased from 0.7% to 25.0%, respectively (EAPC, +23.9%; P<.001). In analyses stratified according to regions, the highest increase in IPC use was recorded in the Northeast (EAPC, +44.0%), followed by the West (EAPC, +26.8%), South (EAPC, +22.9%), and Midwest (EAPC, +15.5%). Moreover, the lowest rate of IPC adoption in 2015 was recorded in the Midwest (14.3%). In multivariable logistic regression models, teaching status (odds ratio [OR], 1.97; P<.001), more recent diagnosis (2010-2015; OR, 3.89; P<.001), and presence of liver metastases (OR, 1.77; P=.02) were associated with higher IPC rates. Conversely, Hispanic race (OR, 0.42; P=.03) and being hospitalized in the Northeast (OR, 0.36; P=.01) were associated with lower rate of IPC adoption. Finally, patients with a primary admission diagnosis that consisted of infection (OR, 2.05; P=.002), cardiovascular disorders (OR, 2.10; P=.03), or pulmonary disorders (OR, 2.81; P=.005) were more likely to receive IPC. CONCLUSIONS: The rate of IPC use in patients with mUCB receiving CCTs sharply increased between 2004 and 2015. The presence of liver metastases, infections, or cardiopulmonary disorders as admission diagnoses represented independent predictors of higher IPC use. Conversely, Hispanic race, nonteaching hospital status, and hospitalization in the Midwest were identified as independent predictors of lower IPC use and represent targets for efforts to improve IPC delivery in patients with mUCB receiving CCT.

Survival effect of perioperative systemic chemotherapy on overall mortality in locally advanced and/or positive regional lymph node non-metastatic urothelial carcinoma of the upper urinary tract.

OBJECTIVES: To analyze the potential survival benefit of perioperative chemotherapy (CHT) in patients treated with nephroureterectomy (NU) for non-metastatic locally advanced upper tract urothelial carcinoma. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2014), we identified 1286 patients with T3 or T4, N 0-3 M0 UTUC. Kaplan-Meier plots, as well as multivariable Cox regression models (MCRMs) relying on inverse probability after treatment weighting (IPTW) and landmark analyses, were used to test the effect of CHT vs no CHT on overall mortality (OM) in the overall population (n =1286), as well as after stratification according to lymph node invasion (LNI). RESULTS: Overall, 37.4% patients received CHT. The CHT rate was higher with LNI (62.2% vs 35.2%, p < 0.001). In MCRMs, testing for OM in the overall population, CHT was associated with lower rates of OM (HR 0.71, CI 0.58-0.87; p = 0.001). Similarly, in MCRMs testing for OM in patients with LNI, CHT achieved independent predictor status for lower OM (HR 0.61, CI 0.48-0.78; p < 0.001). Conversely, in MCRMs testing for OM in patients without LNI, no CHT effect was recorded (HR 0.72, CI 0.52-1.01; p = 0.05). All results were confirmed after IPTW adjustment and in landmark analyses. CONCLUSIONS: Our results represent a contemporary North American report indicating lower OM after CHT for patients with locally advanced non-metastatic upper tract urothelial carcinoma, specifically in patients with T3-T4, N1-N3, M0 disease. Validation of the current and of the previous study is required within a randomized prospective design.