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Angela Pecoraro, Francesco Porpiglia, and Pierre I. Karakiewicz

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Carlotta Palumbo, Francesco A. Mistretta, Sophie Knipper, Angela Pecoraro, Zhe Tian, Shahrokh F. Shariat, Fred Saad, Claudio Simeone, Alberto Briganti, Alessandro Antonelli, and Pierre I. Karakiewicz

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.

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Elio Mazzone, Sophie Knipper, Francesco A. Mistretta, Carlotta Palumbo, Zhe Tian, Andrea Gallina, Derya Tilki, Shahrokh F. Shariat, Francesco Montorsi, Fred Saad, Alberto Briganti, and Pierre I. Karakiewicz

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.

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Angela Pecoraro, Giuseppe Rosiello, Stefano Luzzago, Marina Deuker, Franciska Stolzenbach, Zhe Tian, Shahrokh F. Shariat, Fred Saad, Alberto Briganti, Anil Kapoor, Cristian Fiori, Francesco Porpiglia, and Pierre I. Karakiewicz

Background: The NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer recommend active surveillance as an option for initial management of T1a 0- to 2-cm renal lesions, in addition to partial nephrectomy, radical nephrectomy, and focal ablation. However, contemporary data regarding the distribution of patient and renal cell carcinoma characteristics within this special patient group are scarce. Methods: Within the SEER database (2002–2016), 13,364 patients with T1aNanyMany 0- to 2-cm renal lesions treated with nephrectomy were identified. Data were tabulated according to histologic subtype, Fuhrman grade (FG1–2 vs FG3–4), age category, and sex. In addition, rates of synchronous metastases were quantified. Results: Overall, clear-cell (69.3%), papillary (21.4%), chromophobe (6.9%), multilocular cystic (2.0%), sarcomatoid dedifferentiation (0.2%), and collecting-duct histologic subtypes (0.2%) were identified. Advanced age was associated with a lower rate of FG1–2 clear cell histologic subtype (70.8%–50.3%) but higher rates of FG1–2 papillary (11.1%–23.9%) and chromophobe histologic subtypes (6.2%–8.5%). Overall, 14.5% individuals harbored FG3–4 clear cell (9.8%) or FG3–4 papillary histologic subtypes (4.8%), and both were more prevalent in men. FG3–4 clear-cell and FG3–4 papillary histologic subtypes increased with age, more so in women than in men. The overall rate of synchronous metastases was 0.4% and ranged from 0 in the multilocular cystic subtype to 0.9% in the FG3–4 papillary histologic subtype, respectively, except for 13.8% in the sarcomatoid dedifferentiation histologic subtype. Conclusions: Most T1a 0- to 2-cm renal cell carcinoma represents the low-grade clear-cell or low-grade papillary histologic subtype, with an FG3–4 minority. Even in patients with the FG3–4 histologic subtype, rates of synchronous metastases are virtually zero.

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Paolo Dell'Oglio, Zhe Tian, Sami-Ramzi Leyh-Bannurah, Vincent Trudeau, Alessandro Larcher, Marco Moschini, Ettore Di Trapani, Umberto Capitanio, Alberto Briganti, Francesco Montorsi, Fred Saad, and Pierre I. Karakiewicz

Background: The Deyo adaptation of the Charlson comorbidity index (DaCCI), which relies on 17 comorbid condition groupings, represents one of the most frequently used baseline comorbidity assessment tools in retrospective database studies. However, this index is not specific for patients with bladder cancer (BCa) treated with radical cystectomy (RC). The goal of this study was to develop a short-form of the original DaCCI (DaCCI-SF) that may specifically predict 90-day mortality after RC, with equal or better accuracy. Patients and Methods: Between 2000 and 2009, we identified 7,076 patients in the SEER-Medicare database with stage T1 through T4 nonmetastatic BCa treated with RC. We randomly divided the population into development (n=6,076) and validation (n=1,000) cohorts. Within the development cohort, logistic regression models tested the ability to predict 90-day mortality with various iterations of the DaCCI-SF, wherein <17 original comorbid condition groupings were included after adjusting for age, sex, race, T stage, and N stage. We relied on the Akaike information criterion to identify the most parsimonious and informative set of comorbid condition groupings. Accuracy of the DaCCI and the DaCCI-SF was tested in the external validation cohort. Results: Within the development cohort, the most parsimonious and informative model resulted in the inclusion of 3 of the 17 (17.6%) original comorbid condition groupings: congestive heart failure, cerebrovascular disease, and chronic pulmonary disease. Within the validation cohort, the accuracy was 68.4% for the DaCCI versus 69.7% for the DaCCI-SF. Higher accuracy of the DaCCI-SF was confirmed in subgroup analyses performed according to age (≤75 vs >75 years), stage (organ-confined vs non–organ-confined), type of diversion (ileal-conduit vs non–ileal-conduit), and treatment period. Conclusions: DaCCI-SF relies on 17.6% of the original comorbid condition groupings and provides higher accuracy for predicting 90-day mortality after RC compared with the original DaCCI, especially in most contemporary patients.

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Lara Franziska Stolzenbach, Giuseppe Rosiello, Angela Pecoraro, Carlotta Palumbo, Stefano Luzzago, Marina Deuker, Zhe Tian, Anne-Sophie Knipper, Raisa Pompe, Kevin C. Zorn, Shahrokh F. Shariat, Felix K.H. Chun, Markus Graefen, Fred Saad, and Pierre I. Karakiewicz

Background: Misclassification rates defined as upgrading, upstaging, and upgrading and/or upstaging have not been tested in contemporary Black patients relative to White patients who fulfilled criteria for very-low-risk, low-risk, or favorable intermediate-risk prostate cancer. This study aimed to address this void. Methods: Within the SEER database (2010–2015), we focused on patients with very low, low, and favorable intermediate risk for prostate cancer who underwent radical prostatectomy and had available stage and grade information. Descriptive analyses, temporal trend analyses, and multivariate logistic regression analyses were used. Results: Overall, 4,704 patients with very low risk (701 Black vs 4,003 White), 17,785 with low risk (2,696 Black vs 15,089 White), and 11,040 with favorable intermediate risk (1,693 Black vs 9,347 White) were identified. Rates of upgrading and/or upstaging in Black versus White patients were respectively 42.1% versus 37.7% (absolute Δ = +4.4%; P<.001) in those with very low risk, 48.6% versus 46.0% (absolute Δ = +2.6%; P<.001) in those with low risk, and 33.8% versus 35.3% (absolute Δ = –1.5%; P=.05) in those with favorable intermediate risk. Conclusions: Rates of misclassification were particularly elevated in patients with very low risk and low risk, regardless of race, and ranged from 33.8% to 48.6%. Recalibration of very-low-, low-, and, to a lesser extent, favorable intermediate-risk active surveillance criteria may be required. Finally, our data indicate that Black patients may be given the same consideration as White patients when active surveillance is an option. However, further validations should ideally follow.

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Marina Deuker, Giuseppe Rosiello, Lara Franziska Stolzenbach, Thomas Martin, Claudia Collà Ruvolo, Luigi Nocera, Zhe Tian, Frederik C. Roos, Andreas Becker, Luis A. Kluth, Derya Tilki, Shahrokh F. Shariat, Fred Saad, Felix K.H. Chun, and Pierre I. Karakiewicz

Background: The distribution of metastatic sites in upper tract urothelial carcinoma (UTUC) is not well-known. Consequently, the effects of sex and age on the location of metastases is also unknown. This study sought to investigate age- and sex-related differences in the distribution of metastases in patients with UTUC. Materials and Methods: Within the Nationwide Inpatient Sample database (2000–2015), we identified 1,340 patients with metastatic UTUC. Sites of metastasis were assessed according to age (≤63, 64–72, 73–79, and ≥80 years) and sex. Comparison was performed with trend and chi-square tests. Results: Of 1,340 patients with metastatic UTUC, 790 (59.0%) were men (median age, 71 years) and 550 (41.0%) were women (median age, 74 years). The lung was the most common site of metastases in men and women (28.2% and 26.4%, respectively), followed by bone in men (22.3% vs 18.0% of women) and liver in women (24.4% vs 20.5% of men). Increasing age was associated with decreasing rates of brain metastasis in men (from 6.5% to 2.9%; P=.03) and women (from 5.9% to 0.7%; P=.01). Moreover, increasing age in women, but not in men, was associated with decreasing rates of lung (from 33.3% to 24.3%; P=.02), lymph node (from 28.9% to 15.8%; P=.01), and bone metastases (from 22.2% to 10.5%; P=.02). Finally, rates of metastases in multiple organs did not vary with age or sex (65.2% in men vs 66.5% in women). Conclusions: Lung, bone, and liver metastases are the most common metastatic sites in both sexes. However, the distribution of metastases varies according to sex and age. These observations apply to everyday clinical practice and may be used, for example, to advocate for universal bone imaging in patients with UTUC. Moreover, our findings may also be used for design considerations of randomized trials.