f6873617a0c707e848d7e7dcd747a1c6 325951.pdf f3dd337610f1033379960045aedddf47ecd25707 325951.pdf 93eb88f7e7eac73ed48d3baaf09a8fb4760bb45e573cfc641957a65a34e2d8df 325951.pdf Title: Systematic Review on Upper Urinary Tract Carcinoma in Kidney Transplant Recipients Subject: Objectives: Upper urinary tract urothelial cell carcinoma (UTUC) in kidney transplant recipients (KTRs) presents distinct clinical challenges due to the complexities of managing both cancer and the long-term immunosuppressive therapy required to preserve graft function. UTUC in this population often presents at advanced stages, contributing to poorer outcomes compared to immunocompetent individuals. Methods: This systematic review (SR) evaluates the incidence, clinical presentation, treatment approaches, and survival outcomes of UTUC in KTRs, based on 16 retrospective studies including 526 patients. Results: The present study highlights a predominance of female patients (ranging from 50% to 91.6%) and significant variability in time to diagnosis (from 7 to 181 months post-transplant). Tumor characteristics also showed considerable heterogeneity, with high-grade and advanced-stage (T3–T4) tumors being more common. The standard treatment for UTUC in KTRs remains radical nephroureterectomy (RNU), with additional resection of the bladder (TURB) when bladder cancer (BC) coexists. Survival outcomes vary significantly, with 5-year overall survival (OS) rates ranging from 16.7% to 90.9%, strongly influenced by tumor stage at diagnosis. This SR further reports high rates of bladder recurrence (18.8% to 61.2%) and challenges in balancing effective cancer treatment with graft preservation. The variability in immunosuppressive regimens across studies complicates the assessment of their role in UTUC progression. The limitations of the current evidence include small sample sizes, retrospective designs, and inconsistent follow-up durations. Conclusions: This SR underscores the need for tailored treatment strategies and improved long-term surveillance. Future research should focus on prospective studies with larger cohorts, exploring the impact of immunosuppression and novel therapies on UTUC outcomes in KTRs. Keywords: upper urinary tract urothelial cell carcinoma; kidney transplantation; nephroureterectomy; recipients Author: Alberto Piana, Alicia López-Abad, Battista Lanzillotta, Alessio Pecoraro, Thomas Prudhomme, Hakan Bahadır Haberal, Michele Di Dio, Beatriz Bañuelos Marco, Muhammet Irfan Dönmez, Alberto Breda and Angelo Territo Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Jun 3 13:28:56 2025 CEST ModDate: Tue Jun 3 13:52:01 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1854763 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- LDAEIS+VnURWPalladioL Type 1 Custom yes yes yes 10 0 HJPRAL+URWPalladioL-Roma Type 1 Custom yes yes yes 16 0 LQWORF+URWPalladioL-Bold Type 1 Custom yes yes yes 22 0 ZREGDQ+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 XQBIYI+CMSY10 Type 1 Builtin yes yes yes 53 0 JLMOND+ArialMT TrueType WinAnsi yes yes no 64 0 JLMPLA+Arial-ItalicMT TrueType WinAnsi yes yes no 67 0 JLMPNB+Arial-BoldMT TrueType WinAnsi yes yes no 70 0 JLMODO+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 73 0 JLMODP+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 79 0 JLMOCN+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 112 0 JLMODO+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 118 0 JLMODP+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 124 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 138 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-02-25 04:13:18 CET RepresentationInformation: 325951.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-02-24 12:23:40 CET Size: 1854763 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 339 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Search Strategy Destination: subsection.2.1 Item: Title: Study Selection Destination: subsection.2.2 Item: Title: Risk-of-Bias Assessment Destination: subsection.2.3 Item: Title: Data Extraction and Analysis Destination: subsection.2.4 Item: Title: Evidence Synthesis Destination: section.3 Children: Item: Title: Risk of Bias and Confounding Assessment Destination: subsection.3.1 Item: Title: Study Characteristics Destination: subsection.3.2 Item: Title: Tumor Characteristics Destination: subsection.3.3 Item: Title: Treatment Approaches Destination: subsection.3.4 Item: Title: Follow-Up and Survival Outcomes Destination: subsection.3.5 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Systematic Review on Upper Urinary Tract Carcinoma in Kidney Transplant Recipients Author: Alberto Piana, Alicia López-Abad, Battista Lanzillotta, Alessio Pecoraro, Thomas Prudhomme, Hakan Bahadır Haberal, Michele Di Dio, Beatriz Bañuelos Marco, Muhammet Irfan Dönmez, Alberto Breda and Angelo Territo Subject: Objectives: Upper urinary tract urothelial cell carcinoma (UTUC) in kidney transplant recipients (KTRs) presents distinct clinical challenges due to the complexities of managing both cancer and the long-term immunosuppressive therapy required to preserve graft function. UTUC in this population often presents at advanced stages, contributing to poorer outcomes compared to immunocompetent individuals. Methods: This systematic review (SR) evaluates the incidence, clinical presentation, treatment approaches, and survival outcomes of UTUC in KTRs, based on 16 retrospective studies including 526 patients. Results: The present study highlights a predominance of female patients (ranging from 50% to 91.6%) and significant variability in time to diagnosis (from 7 to 181 months post-transplant). Tumor characteristics also showed considerable heterogeneity, with high-grade and advanced-stage (T3 T4) tumors being more common. The standard treatment for UTUC in KTRs remains radical nephroureterectomy (RNU), with additional resection of the bladder (TURB) when bladder cancer (BC) coexists. Survival outcomes vary significantly, with 5-year overall survival (OS) rates ranging from 16.7% to 90.9%, strongly influenced by tumor stage at diagnosis. This SR further reports high rates of bladder recurrence (18.8% to 61.2%) and challenges in balancing effective cancer treatment with graft preservation. The variability in immunosuppressive regimens across studies complicates the assessment of their role in UTUC progression. The limitations of the current evidence include small sample sizes, retrospective designs, and inconsistent follow-up durations. Conclusions: This SR underscores the need for tailored treatment strategies and improved long-term surveillance. Future research should focus on prospective studies with larger cohorts, exploring the impact of immunosuppression and novel therapies on UTUC outcomes in KTRs. Keywords: upper urinary tract urothelial cell carcinoma; kidney transplantation; nephroureterectomy; recipients Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Jun 03 13:28:56 CEST 2025 ModDate: Tue Jun 03 13:52:01 CEST 2025 ID: 0xb0ec2fc9e07847057a9070f59fda8226, 0xb0ec2fc9e07847057a9070f59fda8226 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: HJPRAL+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: HJPRAL+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: XQBIYI+CMSY10 FontSubset: true FirstChar: 6 LastChar: 21 FontDescriptor: FontName: XQBIYI+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true ToUnicode: true Font: BaseFont: LQWORF+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 246 FontDescriptor: FontName: LQWORF+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: LDAEIS+VnURWPalladioL FontSubset: true FirstChar: 182 LastChar: 225 FontDescriptor: FontName: LDAEIS+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: URYLRZ+URWPalladioL-BoldItal FontSubset: true FirstChar: 110 LastChar: 110 FontDescriptor: FontName: URYLRZ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: ZREGDQ+URWPalladioL-Ital FontSubset: true FirstChar: 45 LastChar: 121 FontDescriptor: FontName: ZREGDQ+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 99, 177, 152, 186 Annotation: Subtype: Link Rect: 34, 165, 102, 174 Annotation: Subtype: Link Rect: 36, 75, 152, 84 Annotation: Subtype: Link Rect: 34, 63, 89, 72 Annotation: Subtype: Link Rect: 34, 773, 179, 809 Annotation: Subtype: Link Rect: 515, 773, 560, 809 Annotation: Subtype: Link Rect: 110, 663, 121, 677 Annotation: Subtype: Link Rect: 217, 663, 228, 677 Annotation: Subtype: Link Rect: 149, 650, 160, 663 Annotation: Subtype: Link Rect: 241, 650, 252, 663 Annotation: Subtype: Link Rect: 423, 27, 560, 37 Annotation: Subtype: Link Rect: 34, 367, 87, 386 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 244, 647, 251, 656 ActionDest: 159 Annotation: Subtype: Link Rect: 529, 605, 536, 614 ActionDest: 159 Annotation: Subtype: Link Rect: 308, 550, 315, 558 ActionDest: 159 Annotation: Subtype: Link Rect: 213, 521, 220, 531 ActionDest: 159 Annotation: Subtype: Link Rect: 221, 522, 228, 531 ActionDest: 159 Annotation: Subtype: Link Rect: 488, 337, 495, 346 ActionDest: 159 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 481, 683, 488, 695 ActionDest: 58 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 408, 711, 415, 723 ActionDest: 106 Annotation: Subtype: Link Rect: 393, 112, 399, 120 ActionDest: 159 Annotation: Subtype: Link Rect: 399, 112, 406, 120 ActionDest: 159 Annotation: Subtype: Link Rect: 408, 112, 419, 120 ActionDest: 162 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 540, 683, 547, 695 ActionDest: 58 Annotation: Subtype: Link Rect: 455, 624, 462, 636 ActionDest: 106 Annotation: Subtype: Link Rect: 548, 570, 555, 582 ActionDest: 146 Annotation: Subtype: Link Rect: 464, 544, 476, 553 ActionDest: 159 Annotation: Subtype: Link Rect: 194, 531, 206, 540 ActionDest: 159 Annotation: Subtype: Link Rect: 542, 517, 554, 526 ActionDest: 159 Annotation: Subtype: Link Rect: 281, 503, 293, 512 ActionDest: 159 Annotation: Subtype: Link Rect: 231, 475, 238, 484 ActionDest: 159 Annotation: Subtype: Link Rect: 406, 461, 418, 470 ActionDest: 159 Annotation: Subtype: Link Rect: 215, 447, 227, 456 ActionDest: 159 Annotation: Subtype: Link Rect: 226, 391, 233, 400 ActionDest: 159 Annotation: Subtype: Link Rect: 236, 391, 243, 400 ActionDest: 159 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 48, 366, 54, 372 ActionDest: 159 Annotation: Subtype: Link Rect: 48, 250, 54, 257 ActionDest: 159 Annotation: Subtype: Link Rect: 46, 174, 55, 181 ActionDest: 159 Annotation: Subtype: Link Rect: 46, 107, 55, 113 ActionDest: 159 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 46, 413, 55, 420 ActionDest: 159 Annotation: Subtype: Link Rect: 46, 346, 55, 353 ActionDest: 159 Annotation: Subtype: Link Rect: 46, 290, 55, 297 ActionDest: 159 Annotation: Subtype: Link Rect: 46, 170, 55, 177 ActionDest: 159 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 48, 421, 54, 428 ActionDest: 159 Annotation: Subtype: Link Rect: 46, 377, 55, 384 ActionDest: 159 Annotation: Subtype: Link Rect: 46, 338, 55, 345 ActionDest: 159 Annotation: Subtype: Link Rect: 46, 298, 55, 305 ActionDest: 159 Annotation: Subtype: Link Rect: 46, 258, 55, 265 ActionDest: 159 Annotation: Subtype: Link Rect: 46, 218, 55, 225 ActionDest: 162 Annotation: Subtype: Link Rect: 48, 178, 54, 185 ActionDest: 159 Annotation: Subtype: Link Rect: 48, 138, 54, 145 ActionDest: 159 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 531, 741, 543, 751 ActionDest: 159 Annotation: Subtype: Link Rect: 196, 728, 208, 737 ActionDest: 159 Annotation: Subtype: Link Rect: 441, 714, 448, 723 ActionDest: 159 Annotation: Subtype: Link Rect: 495, 714, 507, 723 ActionDest: 159 Annotation: Subtype: Link Rect: 524, 700, 531, 709 ActionDest: 159 Annotation: Subtype: Link Rect: 549, 686, 556, 695 ActionDest: 159 Annotation: Subtype: Link Rect: 209, 672, 221, 681 ActionDest: 159 Annotation: Subtype: Link Rect: 302, 658, 314, 667 ActionDest: 159 Annotation: Subtype: Link Rect: 412, 658, 424, 667 ActionDest: 159 Annotation: Subtype: Link Rect: 524, 644, 536, 653 ActionDest: 159 Annotation: Subtype: Link Rect: 190, 630, 197, 639 ActionDest: 159 Annotation: Subtype: Link Rect: 454, 616, 461, 625 ActionDest: 159 Annotation: Subtype: Link Rect: 223, 602, 230, 611 ActionDest: 159 Annotation: Subtype: Link Rect: 239, 437, 251, 445 ActionDest: 159 Annotation: Subtype: Link Rect: 241, 408, 253, 418 ActionDest: 159 Annotation: Subtype: Link Rect: 221, 381, 233, 390 ActionDest: 159 Annotation: Subtype: Link Rect: 538, 312, 545, 321 ActionDest: 159 Annotation: Subtype: Link Rect: 222, 298, 229, 307 ActionDest: 159 Annotation: Subtype: Link Rect: 191, 285, 198, 294 ActionDest: 159 Annotation: Subtype: Link Rect: 402, 271, 409, 280 ActionDest: 159 Annotation: Subtype: Link Rect: 388, 257, 400, 266 ActionDest: 159 Annotation: Subtype: Link Rect: 387, 243, 399, 252 ActionDest: 162 Annotation: Subtype: Link Rect: 453, 243, 465, 252 ActionDest: 159 Annotation: Subtype: Link Rect: 252, 201, 259, 210 ActionDest: 159 Annotation: Subtype: Link Rect: 482, 201, 489, 210 ActionDest: 159 Annotation: Subtype: Link Rect: 223, 173, 235, 182 ActionDest: 159 Annotation: Subtype: Link Rect: 497, 173, 509, 182 ActionDest: 159 Annotation: Subtype: Link Rect: 298, 159, 310, 168 ActionDest: 159 Annotation: Subtype: Link Rect: 396, 145, 408, 154 ActionDest: 159 Annotation: Subtype: Link Rect: 460, 145, 472, 154 ActionDest: 159 Annotation: Subtype: Link Rect: 533, 131, 545, 140 ActionDest: 159 Annotation: Subtype: Link Rect: 189, 117, 201, 126 ActionDest: 159 Annotation: Subtype: Link Rect: 266, 117, 278, 126 ActionDest: 159 Annotation: Subtype: Link Rect: 472, 104, 484, 112 ActionDest: 159 Annotation: Subtype: Link Rect: 344, 89, 356, 99 ActionDest: 159 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 444, 672, 456, 681 ActionDest: 159 Annotation: Subtype: Link Rect: 468, 658, 480, 667 ActionDest: 162 Annotation: Subtype: Link Rect: 254, 574, 266, 583 ActionDest: 162 Annotation: Subtype: Link Rect: 493, 546, 500, 556 ActionDest: 159 Annotation: Subtype: Link Rect: 501, 546, 513, 556 ActionDest: 159 Annotation: Subtype: Link Rect: 513, 547, 525, 556 ActionDest: 159 Annotation: Subtype: Link Rect: 193, 477, 205, 486 ActionDest: 159 Annotation: Subtype: Link Rect: 257, 477, 269, 486 ActionDest: 159 Annotation: Subtype: Link Rect: 339, 477, 351, 486 ActionDest: 162 Annotation: Subtype: Link Rect: 423, 477, 430, 486 ActionDest: 159 Annotation: Subtype: Link Rect: 268, 393, 280, 402 ActionDest: 162 Annotation: Subtype: Link Rect: 238, 366, 250, 374 ActionDest: 159 Annotation: Subtype: Link Rect: 415, 365, 427, 374 ActionDest: 159 Annotation: Subtype: Link Rect: 305, 296, 317, 305 ActionDest: 159 Annotation: Subtype: Link Rect: 356, 254, 368, 263 ActionDest: 162 Annotation: Subtype: Link Rect: 368, 254, 380, 263 ActionDest: 162 Annotation: Subtype: Link Rect: 379, 156, 391, 166 ActionDest: 159 Annotation: Subtype: Link Rect: 396, 143, 403, 152 ActionDest: 159 Annotation: Subtype: Link Rect: 351, 87, 363, 96 ActionDest: 162 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 280, 731, 287, 740 ActionDest: 159 Annotation: Subtype: Link Rect: 365, 717, 371, 726 ActionDest: 159 Annotation: Subtype: Link Rect: 418, 703, 430, 712 ActionDest: 162 Annotation: Subtype: Link Rect: 431, 703, 443, 712 ActionDest: 162 Annotation: Subtype: Link Rect: 443, 703, 455, 712 ActionDest: 162 Annotation: Subtype: Link Rect: 370, 661, 382, 670 ActionDest: 162 Annotation: Subtype: Link Rect: 454, 605, 466, 614 ActionDest: 162 Annotation: Subtype: Link Rect: 536, 187, 560, 198 Annotation: Subtype: Link Rect: 165, 173, 374, 184 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 86, 671, 123, 681 Annotation: Subtype: Link Rect: 129, 671, 165, 681 Annotation: Subtype: Link Rect: 86, 632, 123, 642 Annotation: Subtype: Link Rect: 130, 632, 166, 642 Annotation: Subtype: Link Rect: 259, 594, 296, 604 Annotation: Subtype: Link Rect: 265, 555, 303, 566 Annotation: Subtype: Link Rect: 59, 517, 96, 527 Annotation: Subtype: Link Rect: 402, 491, 439, 502 Annotation: Subtype: Link Rect: 59, 453, 96, 464 Annotation: Subtype: Link Rect: 102, 453, 138, 464 Annotation: Subtype: Link Rect: 241, 427, 279, 438 Annotation: Subtype: Link Rect: 364, 402, 402, 413 Annotation: Subtype: Link Rect: 127, 364, 164, 374 Annotation: Subtype: Link Rect: 139, 326, 176, 336 Annotation: Subtype: Link Rect: 478, 287, 515, 298 Annotation: Subtype: Link Rect: 521, 287, 557, 298 Annotation: Subtype: Link Rect: 428, 261, 465, 272 Annotation: Subtype: Link Rect: 517, 236, 555, 247 Annotation: Subtype: Link Rect: 401, 210, 438, 221 Annotation: Subtype: Link Rect: 445, 210, 481, 221 Annotation: Subtype: Link Rect: 388, 185, 425, 196 Annotation: Subtype: Link Rect: 431, 185, 467, 196 Annotation: Subtype: Link Rect: 244, 159, 281, 170 Annotation: Subtype: Link Rect: 378, 121, 416, 132 Annotation: Subtype: Link Rect: 104, 83, 141, 93 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 104, 731, 141, 742 Annotation: Subtype: Link Rect: 118, 680, 155, 690 Annotation: Subtype: Link Rect: 161, 680, 197, 690 Annotation: Subtype: Link Rect: 245, 654, 282, 665 Annotation: Subtype: Link Rect: 288, 654, 324, 665 Annotation: Subtype: Link Rect: 144, 616, 182, 627 Annotation: Subtype: Link Rect: 379, 577, 417, 588 Annotation: Subtype: Link Rect: 316, 552, 354, 563 Annotation: Subtype: Link Rect: 360, 552, 396, 563 Annotation: Subtype: Link Rect: 213, 514, 251, 524 Annotation: Subtype: Link Rect: 432, 475, 470, 486 Annotation: Subtype: Link Rect: 477, 424, 514, 435 Annotation: Subtype: Link Rect: 498, 399, 536, 410 Annotation: Subtype: Link Rect: 465, 360, 503, 371 Annotation: Subtype: Link Rect: 269, 322, 306, 333 Checksum: a434357b Type: CRC32 Checksum: f6873617a0c707e848d7e7dcd747a1c6 Type: MD5 Checksum: f3dd337610f1033379960045aedddf47ecd25707 Type: SHA-1 Checksum: 93eb88f7e7eac73ed48d3baaf09a8fb4760bb45e573cfc641957a65a34e2d8df Type: SHA-256