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Tilki, Derya

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    Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: report of the advanced prostate cancer consensus conference (apccc) 2022
    (Elsevier, 2023) Gillessen, Silke; Bossi, Alberto; Davis, Ian D.; de Bono, Johann; Fizazi, Karim; James, Nicholas D.; Mottet, Nicolas; Shore, Neal; Small, Eric; Smith, Matthew; Sweeney, Christopher J.; Tombal, Bertrand; Antonarakis, Emmanuel S.; Aparicio, Ana M.; Armstrong, Andrew J.; Attard, Gerhardt; Beer, Tomasz M.; Beltran, Himisha; Bjartell, Anders; Blanchard, Pierre; Briganti, Alberto; Bristow, Rob G.; Bülbül, Muhammad; Caffo, Orazio; Castellano, Daniel; Castro, Elena; Cheng, Heather H.; Chi, Kim N; Chowdhury, Simon; Clarke, Caroline S.; Clarke, Noel; Daugaard, Gedske; De Santis, Maria; Duran, Ignacio; Eeles, Ross; Efstathiou, Eleni; Efstathiou, Jason; Ekeke, Onyeanunam Ngozi; Evans, Christopher P.; Fanti, Stefano; Feng, Felix Y.; Fonteyne, Valerie; Fossati, Nicola; Frydenberg, Mark; George, Dan; Gleave, Martin; Gravis, Gwenaelle; Halabi, Susan; Heinrich, Daniel; Herrmann, Ken; Higano, Celestia; Hofman, Michael S.; Horvath, Lisa G.; Hussain, Maha; Jereczek-Fossa, Barbara A.; Jones, Rob; Kanesvaran, Ravindran; Kellokumpu-Lehtinen, Pirkko-Liisa; Khauli, Raja B.; Klotz, Laurence; Kramer, Gero; Leibowitz, Raja; Logothetis, Christopher; Mahal, Brandon; Maluf, Fernando; Mateo, Joaquin; Matheson, David; Mehra, Niven; Merseburger, Axel; Morgans, Alicia K.; Morris, Michael J.; Mrabti, Hind; Mukherji, Deborah; Murphy, Declan G.; Murthy, Vedang; Nguyen, Paul L.; Oh, William K.; Ost, Piet; O'Sullivan, Joe M.; Padhani, Anwar R.; Pezaro, Carmel J.; Poon, Darren M. C.; Pritchard, Colin C.; Rabah, Danny M.; Rathkopf, Dana; Reiter, Robert E.; Rubin, Mark A.; Ryan, Charles J.; Saad, Fred; Sade, Juan Pablo; Sartor, Oliver; Scher, Howard I.; Sharifi, Nima; Skoneczna, Iwona; Soule, Howard; Spratt, Daniel E.; Srinivas, Sandy; Sternberg, Cora N.; Steuber, Thomas; Suzuki, Hiroyoshi; Sydes, Matthew R.; Taplin, Mary-Ellen; Türkeri, Levent; Turco, Fabio; Uemura, Hiroji; Uemura, Hirotsugu; Ürün, Yüksel; Vale, Claire L.; van Oort, Inge; Vapiwala, Neha; Walz, Jochen; Yamoah, Kosj; Ye, Dingwei; Yu, Evan Y.; Zapatero, Almudena; Zilli, Thomas; Omlin, Aurelius; Tilki, Derya; Other; School of Medicine; Koç University Hospital; N/A
    Background: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. Objective: To present the voting results of the APCCC 2022. Design, Setting, and Participants: The experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. Outcome measurements and statistical analysis: the panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. Results and Limitations: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. Conclusions: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. Patient Summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. Twitter Summary: report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. Take-Home Message: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration-resistant prostate cancer is summarised here.
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    Cancer-specific mortality after cryoablation vs heat-based thermal ablation in T1a renal cell carcinoma
    (Wolters Kluwer Health, 2023) Sorce, Gabriele; Hoeh, Benedikt; Hohenhorst, Lukas; Panunzio, Andrea; Tappero, Stefano; Tian, Zhe; Kokorovic, Andrea; Larcher, Alessandro; Capitanio, Umberto; Terrone, Carlo; Chun, Felix K. H.; Antonelli, Alessandro; Saad, Fred; Shariat, Shahrokh F.; Montorsi, Francesco; Briganti, Alberto; Karakiewicz, Pierre I.; N/A; Tilki, Derya; Other; School of Medicine
    Purpose: Guidelines suggest less favorable cancer control outcomes for local tumor destruction in T1a renal cell carcinoma patients with tumor size 3.1-4 cm. We compared cancer-specific mortality between cryoablation vs heat-based thermal ablation in patients with tumor size 3.1-4 cm, as well as in patients with tumor size ≤3 cm.Materials and Methods:Within the Surveillance, Epidemiology, and End Results database (2004-2018), we identified patients with clinical T1a stage renal cell carcinoma treated with cryoablation or heat-based thermal ablation. After up to 2:1 ratio propensity score matching between patients treated with cryoablation vs heat-based thermal ablation, we addressed cancer-specific mortality relying on competing risks regression models, adjusted for other-cause mortality and other covariates (age, tumor size, tumor grade, and histological subtype).Results:Of 1,468 assessable patients with tumor size 3.1-4 cm, 1,080 vs 388 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 757 cryoablations vs 388 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was associated with higher cancer-specific mortality (HR:2.02, P <.001), relative to cryoablation. of 4,468 assessable patients with tumor size ≤3 cm, 3,354 vs 1,114 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 2,217 cryoablations vs 1,114 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was not associated with higher cancer-specific mortality (HR:1.13, P =.5) relative to cryoablation.Conclusions:Our findings corroborated that in cT1a patients with tumor size 3.1-4 cm, cancer-specific mortality is twofold higher after heat-based thermal ablation vs cryoablation. Conversely, in patients with tumor size ≤3 cm either ablation technique is equally valid. These findings should be considered at clinical decision making and informed consent.
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    Management of patients with advanced prostate cancer. Part I: intermediate-/high-risk and locally advanced disease,biochemical relapse, and side effects of hormonal treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022
    (Elsevier B.V., 2023) Gillessen, Silke; Bossi, Alberto; Davis, Ian D.; de Bono, Johann; Fizazi, Karim; James, Nicholas D.; Mottet, Nicolas; Shore, Neal; Small, Eric; Smith, Mathew; Sweeney, Christopher; Tombal, Bertrand; Antonarakis, Emmanuel S.; Aparicio, Ana M.; Armstrong, Andrew J.; Attard, Gerhardt; Beer, Tomasz M.; Beltran, Himisha; Bjartell, Anders; Blanchard, Pierre; Briganti, Alberto; Bristow, Rob G.; Bulbul, Muhammad; Caffo, Orazio; Castellano, Daniel; Castro, Elena; Cheng, Heather H.; Chi, Kim N.; Chowdhury, Simon; Clarke, Caroline S.; Clarke, Noel; Daugaard, Gedske; De Santis, Maria; Duran, Ignacio; Eeles, Ros; Efstathiou, Eleni; Efstathiou, Jason; Ngozi Ekeke, Onyeanunam; Evans, Christopher P.; Fanti, Stefano; Feng, Felix Y.; Fonteyne, Valerie; Fossati, Nicola; Frydenberg, Mark; George, Daniel; Gleave, Martin; Gravis, Gwenaelle; Halabi, Susan; Heinrich, Daniel; Herrmann, Ken; Higano, Celestia; Hofman, Michael S.; Horvath, Lisa G.; Hussain, Maha; Jereczek-Fossa, Barbara Alicja; Jones, Robert; Kanesvaran, Ravindran; Kellokumpu-Lehtinen, Pirkko-Liisa.; Khauli, Raja B.; Klotz, Laurence; Kramer, Gero; Leibowitz, Raya; Logothetis, Christopher J.; Mahal, Brandon A.; Maluf, Fernando; Mateo, Joaquin; Matheson, David; Mehra, Niven; Merseburger, Axel; Morgans, Alicia K.; Morris, Michael J.; Mrabti, Hind; Mukherji, Deborah; Murphy, Declan G.; Murthy, Vedang; Nguyen, Paul L.; Oh, William K.; Ost, Piet; O'Sullivan, Joe M.; Padhani, Anwar R.; Pezaro, Carmel; Poon, Darren M.C.; Pritchard, Colin C.; Rabah, Danny M.; Rathkopf, Dana; Reiter, Robert E.; Rubin, Mark A.; Ryan, Charles J.; Saad, Fred.; Pablo Sade, Juan; Sartor, Oliver A.; Scher, Howard I.; Sharifi, Nima; Skoneczna, Iwona; Soule, Howard; Spratt, Daniel E.; Srinivas, Sandy; Sternberg, Cora N.; Steuber, Thomas; Suzuki, Hiroyoshi; Sydes, Matthew R.; Taplin, Marry-Ellen; Türkeri, Levent; Turco, Fabio; Uemura, Hiroji; Uemura, Hirotsugu; Ürün, Yüksel; Vale, Claire L.; van Oort, Inge; Vapiwala, Neha; Walz, Jochen; Yamoah, Kosj; Ye, Dingwei; Yu, Evan Y.; Zapatero, Almudena; Zilli, Thomas; Omlin, Aurelius; Tilki, Derya; Other; School of Medicine; Koç University Hospital; N/A
    Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, Setting, and Participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and Limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. Patient Summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.
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    Survival of testicular pure teratoma vs. mixed germ cell tumor patients in primary tumor specimens across all stages
    (Multidisciplinary Digital Publishing Institute (MDPI), 2023) Cano Garcia, Cristina; Barletta, Francesco; İncesu, Reha-Barış; Piccinelli, Mattia Luca; Tappero, Stefano; Panunzio, Andrea; Tian, Zhe; Saad, Fred; Shariat, Shahrokh F.; Antonelli, Alessandro; Terrone, Carlo; De Cobelli, Ottavio; Graefen, Markus; Briganti, Alberto; Wenzel, Mike; Banek, Severine; Kluth, Luis A.; Chun, Felix K. H.; Karakiewicz, Pierre I.; Tilki, Derya; Other; School of Medicine; Koç University Hospital; N/A
    We aimed to test for survival differences between testicular pure teratoma vs. mixed germ cell tumor (GCT) patients in a stage-specific fashion. Pure teratoma and mixed GCT in primary tumor specimens were identified within the Surveillance, Epidemiology, and End Results database (2004–2019). Kaplan–Meier curves depicted five-year overall survival (OS) and subsequently, cumulative incidence plots depicted cancer-specific mortality (CSM) and other-cause mortality (OCM) in a stage-specific fashion. Multivariable competing risks regression (CRR) models were used. Of 9049 patients, 299 (3%) had pure teratoma. In stage I, II and III, five-year OS rates differed between pure teratoma and mixed GCT (stage I: 91.6 vs. 97.2%, p < 0.001; stage II: 100 vs. 95.9%, p < 0.001; stage III: 66.8 vs. 77.8%, p = 0.021). In stage I, survival differences originated from higher OCM (6.4 vs. 1.2%; p < 0.001). Conversely in stage III, survival differences originated from higher CSM (29.4 vs. 19.0%; p = 0.03). In multivariable CRR models, pure teratoma was associated with higher OCM in stage I (Hazard Ratio (HR): 4.83; p < 0.01). Conversely, in stage III, in multivariable CRR models, pure teratoma was associated with higher CSM (HR: 1.92; p = 0.04). In pure teratoma, survival disadvantage in stage I patients relates to OCM. Survival disadvantage in stage III pure teratoma originates from higher CSM.
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    Salvage radical prostatectomy for recurrent prostate cancer following first-line nonsurgical treatment: validation of the European Association of Urology criteria in a large, multicenter, contemporary cohort
    (Elsevier, 2023) Calleris, Giorgio; Marra, Giancarlo; Benfant, Nicole; Rajwa, Pawel; Ahmed, Mohamed; Abreu, Andre; Cacciamani, Giovanni; Ghoreifi, Alireza; Ribeiro, Luis; Westhofen, Thilo; Tourinho-Barbosa, Rafael; Raskin, Yannic; Veerman, Hans; Albisinni, Simone; Smith, Joseph A.; Rouprêt, Morgan; Oderda, Marco; Massari, Emilia; Persad, Raj; Van Der Poel, Henk; Joniau, Steven; Sanchez-Salas, Rafael; Kretschmer, Alexander; Cathcart, Paul; Gill, Inderbir; Karnes, R. Jeffrey; Shariat, Shahrokh F.; Touijer, Karim; Gontero, Paolo; Tilki, Derya; Other; School of Medicine; N/A
    Salvage radical prostatectomy (sRP) is a potentially curative option for locally radiorecurrent prostate cancer (PCa) but is associated with significant morbidity. Therefore, the European Association of Urology (EAU) guidelines recommend restricting sRP to a favorable-prognosis group according to the EAU criteria, but these have been validated considering only biochemical recurrence (BCR). Our aim was to test these criteria in a large, multicenter, contemporary cohort. We retrospectively reviewed 1265 patients who underwent sRP at 14 referral centers (2000–2021), stratified by compliance with the EAU criteria. Our primary outcome was metastasis-free survival (MFS). We included 1030 men, of whom 221 (21.5%) fully met the EAU recommended criteria for sRP and 809 (78.5%) did not. The EAU-compliant group experienced more favorable pathological and functional outcomes (79% vs 63% wearing no pads at 1 yr; p < 0.001) and had significantly better MFS (90% vs 76% at 5 yr; p < 0.001), prostate-specific antigen–free survival (55% vs 38% at 5 yr; p < 0.001), and overall survival (89% vs 84% at 5 yr; p = 0.01). This was verified by Cox regression analysis for MFS (hazard ratio 1.84, 95% confidence interval 1.13–2.99; p = 0.01). We found that adherence to the EAU criteria is associated with a lower risk of BCR and, more importantly, of metastasis after surgery.
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    Cancer-specific mortality in T1a renal cell carcinoma treated with local tumor destruction versus partial nephrectomy
    (Elsevier, 2023) Sorce, Gabriele; Hoeh, Benedikt; Hohenhorst, Lukas; Panunzio, Andrea; Tappero, Stefano; Tian, Zhe; Kokorovic, Andrea; Larcher, Alessandro; Capitanio, Umberto; Terrone, Carlo; Chun, Felix K.H.; Antonelli, Alessandro; Saad, Fred; Shariat, Shahrokh F.; Montorsi, Francesco; Briganti, Alberto; Karakiewicz, Pierre I.; Tilki, Derya; Other; School of Medicine; N/A
    Background: Large-scale analyses addressing cancer-specific mortality (CSM) in T1a renal cell carcinoma (RCC) patients treated with local tumor destruction (LTD), relative to partial nephrectomy (PN), are scarce. Objective: To compare CSM after LTD versus PN. Design, setting, and participants: Within the Surveillance, Epidemiology, and End Results (SEER) database (2004–2018), we identified patients with clinical T1a stage RCC treated with LTD or PN. Outcome measurements and statistical analyses: After 1:1 ratio propensity score matching (PSM) between patients treated with LTD versus PN, competing risks regression (CRR) models addressed CSM, after adjustment for other-cause mortality (OCM) and other covariates (age, tumor size, tumor grade, and histological subtype). Results and limitations: Relative to the 35 984 PN patients, 5936 LTD patients were older and more frequently harbored unknown RCC histological subtype or unknown grade. After 1:1 PSM that resulted in 5352 LTD versus 5352 PN patients, the 10-yr CSM rate was 8.7% versus 5.5%. In multivariable CRR models, LTD was associated with higher CSM, relative to PN (hazard ratio [HR]: 1.58, p < 0.001). Subgroup analyses revealed invariably higher CSM after LTD versus PN in patients with tumor size ≤3 cm (10-yr CSM 7.2% vs 5.3%, multivariable HR: 1.47, p < 0.001) and in patients with tumor size 3.1–4 cm (10-yr CSM 11.4% vs 6.1%, multivariable HR: 1.72, p < 0.001). Lack of information regarding earlier cancer controls, retreatment, tumor location within the kidney, and type of surgery represented limitations. Conclusions: In T1a RCC patients, LTD is invariably associated with higher CSM relative to PN, even after adjustment for OCM and all available patient and tumor characteristics, and regardless of tumor size considerations. However, the magnitude of CSM disadvantage was more pronounced in LTD patients with tumor size 3.1–4 cm than in those with tumor size ≤3 cm. Patient summary: In patients with small renal masses, we observed higher cancer-specific death rates for local tumor destruction (LTD) than for partial nephrectomy. The LTD disadvantage was more pronounced for patients with tumor size 3.1–4 cm, but was also present in those with tumor size ≤3 cm.
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    Differences in overall survival between clear cell metastatic renal cell carcinoma patients versus population-based controls according to race/ethnicity in the United States
    (Elsevier Inc., 2023) Cano Garcia, Cristina; Nimer, Nancy; Piccinelli, Mattia Luca; Tappero, Stefano; Panunzio, Andrea; Barletta, Francesco; Incesu, Reha-Baris; Tian, Zhe; Saad, Fred; Kapoor, Anil; Briganti, Alberto; Terrone, Carlo; Shariat, Shahrokh F.; Antonelli, Alessandro; De Cobelli, Ottavio; Kluth, Luis A.; Becker, Andreas; Chun, Felix K.H.; Karakiewicz, Pierre I.; Tilki, Derya; Other; School of Medicine; Koç University Hospital; N/A
    Purpose: To quantify differences in five-year overall survival (OS) between clear cell metastatic renal cell carcinoma (ccmRCC) patients and age- and sex-matched population-based controls, especially when race/ethnicity is considered. Methods: We relied on the Surveillance, Epidemiology and End Results database (2006–2016) to identify newly diagnosed (2006- 2011) ccmRCC patients of either Caucasian, Hispanic, African American, or Asian/Pacific Islander race/ethnicity. For each case, we simulated an age- and sex-matched control (Monte Carlo simulation), relying on Social Security Administration Life Tables with five-year follow-up. We compared OS between ccmRCC patients and controls. Multivariable Cox regression models tested for race/ethnicity effect on OS. Results: Of 3067 ccmRCC patients, 2167 (71%) were Caucasians vs. 488 (16%) Hispanics vs. 216 (7%) African Americans and 196 (6%) Asians/Pacific Islanders. At five years, OS difference between ccmRCC patients vs. population-based controls was greatest in African Americans (11 vs. 94%, Δ = 84%), followed by Hispanics (16 vs. 94%, Δ = 77%), Caucasians (16 vs. 89%, Δ = 73%) and Asians/Pacific Islanders (19 vs. 88%, Δ = 70%). In multivariable Cox regression models, African Americans exhibited highest Hazard Ratio for death (HR 1.3, p= 0.003). Conclusion: Relative to Life Tables’ derived age- and sex-matched controls, ccmRCC patients exhibit drastically worse OS, especially African Americans.
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    Cancer specific mortality in patients with collecting duct vs. clear cell renal carcinoma
    (Elsevier, 2023) Panunzio, Andrea; Sorce, Gabriele; Tappero, Stefano; Hohenhorst, Lukas; Garcia, Cristina Cano; Piccinelli, Mattia; Tian, Zhe; Tafuri, Alessandro; De Cobelli, Ottavio; Chun, Felix K. H.; Terrone, Carlo; Briganti, Alberto; Kapoor, Anil; Saad, Fred; Shariat, Shahrokh F.; Cerruto, Maria Angela; Antonelli, Alessandro; Karakiewicz, Pierre I.; Tilki, Derya; Other; School of Medicine; Koç University Hospital; N/A
    Background: Collecting duct carcinoma (CDC) is biologically more aggressive than clear cell renal cell carcinoma (ccRCC). We tested for differences in cancer specific mortality (CSM) rates according to CDC vs. ISUP (International Society of Urological Pathology) 4 ccRCC histological subtype. We hypothesized that the survival disadvantage still applies, even after most detailed adjustments. Methods: Within Surveillance, Epidemiology, and End Results database (2004-2018), we identified 380 CDC vs. 6273 ISUP 4 ccRCC patients of all stages. Propensity score matching (age, sex, race/ethnicity, T, N, and M stages, nephrectomy, and systemic therapy status), Kaplan-Meier plots and multivariable Cox regression models were used. Results: All 380 CDC were matched (1:2) with 760 ISUP4 ccRCC patients. Prior to matching CDC patients exhibited higher rates of lymph node invasion (37.6 % vs. 14.7 %, p < 0.001), and of distant metastases (40.8 % vs. 30.4 %, p < 0.001). Systemic therapy rates were higher in CDC (29.5 % vs. 20.5 %, p < 0.001). However, nephrectomy rates were higher in ISUP4 ccRCC patients (97.5 % vs. 84.7 %, p < 0.001). After matching, in multivariable Cox regression models addressing CSM, CDC was associated with a HR of 1.5 (p < 0.001) in the overall population vs. 1.9 (p = 0.014) in stage I-II vs. 1.4 (p = 0.022) in stage III vs. 1.6 in stage IV (p < 0.001), relative to ISUP4 ccRCC. Conclusion: CDC patients exhibited 40-90 % higher CSM than their ISUP4 ccRCC counterparts in the overall analysis, as well as in stage specific analyses. The CSM disadvantage applies despite higher rates of systemic therapy in CDC patients.
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    Triplet or doublet therapy in metastatic hormone-sensitive prostate cancer patients: a systematic review and network meta-analysis
    (Elsevier, 2023) Mandel, Philipp; Hoeh, Benedikt; Wenzel, Mike; Preisser, Felix; Tian, Zhe; Steuber, Thomas; Karakiewicz, Pierre I.; Chun, Felix K.H.; Tilki, Derya; Other; School of Medicine; N/A
    Context: Two recent randomized controlled trials (RCTs) reported overall survival benefit of triplet therapy (androgen receptor axis–targeted therapy agent [ARAT], docetaxel, and androgen deprivation therapy [ADT]) over that of doublet therapy (docetaxel and ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Ranking of therapy options and comparisons between triplet therapy and doublet ARAT and ADT therapy are scarce. Objective: To rank therapy options (triplet vs doublet [docetaxel and ADT] vs doublet [ARAT and ADT]) and address them within formal network meta-analyses (NMAs); subsequently, NMAs were refitted following stratification according to (1) low- and high-volume tumor burden and (2) doublet versus triplet therapy. Evidence acquisition: A systematic literature review (PubMed, MEDLINE, Embase, Web of Science, Scopus, and Cochrane database) of RCT trials that investigated the overall survival efficacy of systemic treatment in the setting of mHSPC was conducted. The study search and inclusion criteria were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Evidence synthesis: Ten RCTs (n = 9702) were identified. The NMA focusing on the overall cohort of mHSPC demonstrated that triplet therapies (darolutamide, docetaxel, and ADT, and abiraterone, docetaxel, and ADT) were ranked first and second (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.44–0.66; HR: 0.60; 95% CI: 0.46–0.78), followed by doublet therapy (ARAT and ADT) and lastly docetaxel and ADT. Owing to missing data within one RCT, the NMA for low- and high-volume mHSPC focused on nine trials. In high-volume disease, triplet therapy (abiraterone, docetaxel, and ADT) was ranked first (HR: 0.52, 95% CI: 0.38–0.71). Conclusions: Triplet therapy, consisting of an ARAT, docetaxel, and ADT, ranked first in systematic treatment in mHSPC. Moreover, triplet therapy might result in more pronounced overall survival benefit than doublet ARAT and ADT therapy in high-volume mHSPC. Patient summary: We compared different systemic therapy options for metastatic hormone-sensitive prostate cancer and concluded that triplet therapy, consisting of androgen receptor axis–targeted therapy agent, docetaxel, and androgen deprivation therapy, seems to be most beneficial for overall survival.
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    Differences in overall survival of T2N0M0 bladder cancer patients vs. population-based controls according to treatment modalities
    (Springer Science and Business Media B.V., 2023) Cano Garcia, Cristina; Piccinelli, Mattia Luca; Tappero, Stefano; Panunzio, Andrea; Barletta, Francesco; İncesu, Reha-Barış; Tian, Zhe; Saad, Fred; Briganti, Alberto; Terrone, Carlo; Shariat, Shahrokh F.; Graefen, Markus; Antonelli, Alessandro; De Cobelli, Ottavio; Kosiba, Marina; Banek, Severine; Kluth, Luis A.; Chun, Felix K.H.; Karakiewicz, Pierre I.; Tilki, Derya; Other; School of Medicine; Koç University Hospital; N/A
    Purpose: It is unknown to what extent overall survival (OS) of organ-confined (T2N0M0) urothelial carcinoma of the urinary bladder (UCUB) patients differs from age- and sex-matched population-based controls, especially when treatment modalities such as radical cystectomy (RC), trimodal therapy (TMT), or radiotherapy (RT) are considered. Methods: Relying on the Surveillance Epidemiology and End Results database (2004–2018), we identified newly diagnosed (2004–2013) T2N0M0 UCUB patients treated with either RC, TMT or RT. For each case, we simulated an age- and sex-matched control (Monte Carlo simulation), relying on Social Security Administration Life Tables with 5 years of follow-up, and compared OS with that of RC-, TMT-, and RT-treated cases. Additionally, we relied on smoothed cumulative incidence plots to display cancer-specific mortality (CSM) and other-cause mortality (OCM) rates for each treatment modality. Results: Of 7153 T2N0M0 UCUB patients, 4336 (61%) underwent RC, 1810 (25%) TMT, and 1007 (14%) RT. At 5 years, OS rate in RC cases was 65% vs. 86% in population-based controls (Δ = 21%); in TMT cases, 32% vs. 74% in population-based controls (Δ = 42%); and in RT, 13% vs. 60% in population-based control (Δ = 47%). Five-year CSM rates were highest in RT (57%), followed by TMT (46%) and RC (24%). Five-year OCM rates were the highest in RT (30%), followed by TMT (22%) and RC (12%). Conclusion: OS of T2N0M0 UCUB patients is substantially less than that of age- and sex-matched population-based controls. The biggest difference affects RT, followed by TMT. A modest difference was recorded in RC and population-based controls.