Index

A pathogenesis, 746–747 Abiraterone acetate PET scan, 748 androgen deprivation therapy, 260, 268–269 prognosis, 750 -resistant cancer, 242, 243 radiotherapy, 749 mCRPC treatment, 86, 284–285 standard of care, 749 mechanism of action, 242–243 surgical resection, 748–749 with prednisone, 243 Advanced penile squamous cell carcinoma research activity, 244 adjuvant chemotherapy, 799 toxicity management, 243 cisplatin-containing regimen, 802 Ablation clinical presentation, 797 local recurrence in kidney, 644 inguinal lymph node dissection, 798 in men with localized prostate carcinoma, 264 local/inguinal recurrence, 801–803 for tumors, follow-up after, 651 magnetic resonance imaging, 797 Abscopal effect, 633 natural history, 796–797 Acid-base balance disturbances, 456–457 neoadjuvant chemotherapy, 799–800 Acinar adenocarcinoma, 162–164 pelvic lymph node dissection, 798 Active surveillance (AS), 559–560 physical examination, 797 Adenosquamous carcinoma, 790 positron emission tomography with computed Adjuvant androgen ablation, 264 tomography, 797–798 Adjuvant chemotherapy primary chemotherapy, 799 advanced penile SCC, 799 radiation therapy, 801 chemotherapy regimens in adjuvant setting, 398 salvage radiation, 802 contemporary retrospective evidence, 394–397 surgical consolidation, 800–801 EORTC 30994 randomized controlled trial, 394 ultrasonography, 797 neoadjuvant vs., 398 Advanced (CS IIC/III) treatment, oncological outcomes, 392–394 693–695 randomized controlled trials, meta-analyses, Adverse event (AE), 52–53 392–394 Afatinib, 849 rationale for use, 392 Age bias, 54 toxicity associated with delivery, 397–398 Alcoholic consumption, renal cell carcinomas by, 483 Adjuvant radiotherapy, postoperative, 217 Alkaline phosphatase (AP), 81 Adrenal metastases, 631–632, 753 Alpha-fetoprotein (AFP), 33, 669 Adrenocortical carcinoma (ACC) Alpha-methylacyl-CoA racemase (AMACR), 169 clinical presentation, 747 Analgesics, renal cell carcinomas, 488 CT scan, 748 Anamnesis, 725 diagnosis, 747 Anaplastic lymphoma kinase gene (ALK), 495 ENSAT staging system, 748 Androgen ablation, 264 epidemiology, 745–746 Androgen deprivation therapy (ADT) fine-needle biopsy aspiration, 748 abiraterone acetate, 260, 268–269 hormonal workup, 747 antiandrogens, 259 imaging studies, 747–748 apalutamide, 261 management, 748 bicalutamide, 260 medical therapy, 749–750 for biochemical recurrence, 265–267 MRI, 748 castration resistent prostate cancer, 269–270

© Springer Nature Switzerland AG 2019 851 A. S. Merseburger, M. Burger (eds.), Urologic Oncology, https://doi.org/10.1007/978-3-319-42623-5 852 Index

Androgen deprivation therapy (ADT) (cont.) AURKA, 174 complete androgen blockade, 262 Autoimmune diseases, 486 continuous, 278 Axitinib, 605, 606 COUGAR-301 and COUGAR-302 trials, 285 cyproterone acetate, 259 enzalutamide, 261 B estrogens, 259 Bacillus Calmette-Guérin (BCG) fatigue, 272 device-assisted intravesical chemotherapy, 347 flutamide, 260 early cystectomy, 345–346 galeterone, 261 electromotive intravesical chemotherapy (EMDA), 347 GETUG-15, 286 failure, 332, 343 GnRH antagonists, 258–259 and recurrence after BCG, 343–344 gynecomastia, 271–272 with IFN-α, 345 hormonal treatment mechanism, 257 intracavitary chemotherapeutic agents, 346 hot flushes, 270–271 intradermal priming, 345 intermittent androgen deprivation therapy (IAD), 262 MCNA, 345 ketoconazole, 261 microwave-induced hyperthermia (MIH), 347 LATITUDE trial, 285 photodynamic therapy, 347 LHRH agonists, 258 radiation therapy, 347 long-term, 216 repeat, 345 neoadjuvant, 280 stage T1 bladder cancer, 330 nonmetastatic prostate cancer, 263 urethral carcinoma, 741 nonsteroidal antiandrogens, 259 BAP1 mutations, 492 orteronel, 260–261 Basaloid PeIN, 786 plus abiraterone and prednisone, 284–285 Basaloid squamous cell carcinoma, 790 plus docetaxel-based chemotherapy, 281–284 Beckwith-Wiedemann syndrome (BWS), 775 prior to surgical therapy, neoadjuvant, 263–264 Bellini duct carcinoma, 494 prostate cancer, 264–265 Beta-emitter, bone metastases, 85 role of, 213 Beta subunit of human chorionic gonadotrophin (β-hCG), sequencing strategies, 285–286 33, 669, 727 sexual dysfunction, 271 Bevacizumab, 605–606 short-term, 216–217 B7-H1, 524 side effects, 262–263 β-HCG, see Beta subunit of human chorionic STAMPEDE trial, 278, 285 gonadotrophin (β-hCG) steroidal antiandrogens, 259 Bias, in clinical trials, 40, 53–56 SWOG trial, 278 Bicalutamide, 260 testosterone-lowering therapy, 258 Bilateral , 258 Androgen receptor, 171–172 Biochemical recurrence (BCR) rate Anesthesia ADT, 265–267 prostate cancer biopsy, 142, 145 definition, 229–230 radical cystectomy, 353 hormone therapy, 236–237 TURBT, 310 management, 230–231 Angiomyolipoma, 491, 492, 510 in postradical patients, 231–232 ANNA/C-TRUS, 146–147 in postradiotherapy patients, 232 Antiandrogens, 259 prostate cancer, 228 Antibiotic prophylaxis Biofeedback training prostate cancer biopsy, 154–155 devices, 444–445 TURBT, 310 principles, 442–443 Antiresorptive therapy BioJet, 152 renal cell carcinoma, 88–89 Biomarkers urothelial carcinoma, 87 prostate cancer Apalutamide, 261 diagnostic, 111–117 APC,115 prognostic, 117–120 APOBEC mutation, 7 renal cell carcinoma ArtemisTM, 151 blood-based, 522 Ascertainment bias, 54 molecular, 517 ATM, 174 tissue-based, 517–520 Atypical metastases, 632 use of, 521 Atypical small acinar proliferation (ASAP), 166–167 BiopSee®, 152 Index 853

Biopsy techniques CEP, 523 prostate cancer cfDNA levels, 523 antibiotic management, 154–155 CTC, 523 complications, 153–154 fascin, 521–522 indications and future perspective, 155–156 IGF-1, 523 targeted biopsy, 146–153 LDH, 522 ultrasound-guided, 142–146 miRNAs, 523–524 during TURBT, 312–313 neutrophils, 522 Birt-Hogg-Dubé disease (BHD), 491 NGAL, 523 Bisphosphonates, 82 SAA, 522–523 Bladder cancer (BC) thrombocytosis, 522 age influence, 294–295 VEGF, 522 age-standardized rates, 293 Body mass index (BMI), 484 cellular-based marker systems, 305 Bone metabolism, 459 current and future burden, 298–299 Bone metastases, 278, 279, 631, 703–704, 716 cytokeratins (CK), 305 with prostate cancer diagnostic tools, 305–306 diagnosis, 80–82 environmental risk factors, 6 epidemiology, 79 ethnicity differences, 297–298 mCRPC treatment, 86 fluorescence cystoscopy (photodynamic diagnosis pathophysiology, 79–80 (PDD)), 306 treatment, 82–86 follow-up, 471–472 with renal cell carcinoma gender influence, 295–296 antiresorptive therapy, 88–89 genome-wide association studies, 6 diagnosis, 88 geographical differences, 296–297 epidemiology, 88 imaging in, 306 local therapy, 88 incidence, 292–294 with urothelial carcinoma, 87 MIBC (see Muscle-invasive bladder cancer (MIBC)) Bone scan, 22 molecular basics, 6–7 bone metastases with prostate cancer, 81 mortality, 292–294 prostate cancer, 31 muscle-invasive bladder cancer, 305 testicular cancer, 33 narrow-band imaging (NBI), 306 Bone scintigraphy, renal cell carcinomas, 506 NMIBC (see Non-muscle-invasive bladder cancer Bone staging, prostate cancer, 131–137 (NMIBC)) Bone-targeting agents, 247 non-muscle-invasive bladder cancer, 305 Bosniak classification, renal cystic lesions, 509 prevalence, 292–294, 304, 374 Brachytherapy, 564–565 protein-based marker systems, 305 advances in, 214 radiosensitization with chemotherapy and salvage, 223 hyperthermia, 378–379 toxicity, 220–222 radiotherapy, 377–378 BRAF gene, 13 socioeconomic aspects, 298 Brain metastases, 631, 704, 716 symptoms, 304–305 BRCA1, 5, 174 transurethral resection of the tumor (TURB), 306 BRCA2, 5, 174 treatment algorithm, 377 Bulky inguinal lymph nodes, 812, 813 types, 424 Bureaucracy bias, 54 urinary cytology (UC), 305 urinary marker tests, 305 urine tests, 305 white light cystoscopy (WLC), 306 C Bladder diverticulum, TURBT in, 312 Cabazitaxel Bladder dome, TURBT in, 312 castration-resistant prostate cancer, 247–249 Bladder preservation, patient selection for, 374 mechanism of action, 247 Blinding trials, 57–58 toxicity management, 249 Blind review, in clinical trials, 40 Cabozantinib, 607 Block randomization, 56 CAF, 523 Blood-based biomarkers, 522 CAIX, see Carbonic anhydrase IX (CAIX) CAF, 523 CAPRA score, 117 CAIX, 522 Carbonic anhydrase IX (CAIX), 519–520, 522, 541 CEC, 523 Carboplatin-combination chemotherapy, 407 854 Index

Carcinoma cuniculatum, 789 Cigarette smoking Carcinoma in situ (CIS) bladder cancer, 296 bladder cancer, 293 renal cell carcinomas, 482–483 clinical implications, 340–341 , 824 cytology, 342 Cisplatin-based chemotherapy, 404–407, 656, 802 definition, 338 Cisplatin, etoposide, and bleomycin (PEB), 697–699 diagnosis, 341 Classic triphasic Wilms tumor, 776 macroscopy, 339 Clear cell carcinoma, 791–792 microscopy, 339 Clear cell renal cell carcinoma (ccRCC), 492–493 molecular biology, 339–340 definition, 542 narrow-band imaging, 341 histopathology, 542–544 photodynamic diagnosis, 341 immunohistochemistry, 542–544 therapy, 342–343 macroscopy, 542 Castration-resistant prostate cancer (CRPC), 269–270 molecular pathology, 542–544 bone-targeting agents, 247 Clear cell urothelial carcinomas, 417–418 cabazitaxel, 247–249 Clinical stage I (CSI) nonseminoma, 686–687 docetaxel, 245–246 Clinical stage I (CSI) enzalutamide, 244–245 carboplatinum monotherapy, 684, 685 “fixed” agents, 247–249 follow-up examinations, 686 “floating” agents, 242 recurrence rates, 684, 685 metastatic, 242 SWENOTECA study, 685 novel technologies and targeted treatments, 249–250 treatment of, 685–686 radium223 dichloride, 246 Clinical stage II disease, definition of, 690 response and progression assessment, 250–251 Clinical trials “semifixed” agents, 245–247 adverse event and patient-reported outcomes, 52–53 sipuleucel-T, 249 bias in, 53–56 treatment sequencing, 251 blinding, 57–58 Caveolin-1, 521 comparator, 47 CCND1, 173 composite variables and co-primary endpoints, 49 CCND2,12 design, 45–48 CCP-score, 119 drug development, 39–41 CEC, 523 ethical foundation, 60–61 Cell adhesion proteins, 541 genomic research, 62–63 Cell cycle proteins, 541 glossary, 40 Cellular-based marker systems, 305 guidelines, 67–70 CEP, 523 medical tumor treatment, 63–67 cfDNA levels, 523 molecular testing, 62 Charlson comorbidity index (CCI), 624 outcome and reporting, 70–71 Chemotherapy patient population, 46–47 advanced penile SCC, 799–800 patient-reported outcomes, 52 device-assisted intravesical, 347 phases, 42–45 renal cell carcinomas, 488 planning and conduction, 65–66 retroperitoneal tumors, 769 primary and secondary endpoints, 48–49 See also Adjuvant chemotherapy randomization, 56–57 Choice/control group bias, 54–55 research question and hypothesis, 45–46 Choice-of-question bias, 54 sample size estimation, 47 Choriocarcinoma, 663 statistical analysis, 47–48 Chromodomain-helicase DNA-binding (CHD) stratification, 58–59 protein 1, 172 surrogate endpoints, 49–51 Chromophobe renal cell carcinoma (chRCC) types, 41–42 definition, 546 Club Urológico Español de Tratamiento Oncológico histopathology, 546–547 (CUETO) model, 427–429 immunohistochemistry, 546–547 C-met, 519 macroscopy, 546 Coal exposure, renal cell carcinomas, 489 molecular pathology, 546–547 Cognitive fusion biopsy, prostate cancer, 149 renal cell carcinomas, 493 Collecting duct carcinoma (cdCA), 548 Chromosomal alterations, in prostate cancer, 171 renal cell carcinomas, 494 Chronic hepatitis C infection, 487 Comparison Arm for ProtecT (CAP), 102 Chronic kidney disease, 485 Complete androgen blockade (CAB), 262 Index 855

Complex renal mass, partial vs. total nephrectomy, renal function and stone formation after, 459 573–575 and urinary diversion, metabolic changes, 456 Computed tomography (CT) urinary tract infection after, 455–456 adrenocortical carcinoma, 748 Cystoscope bladder cancer, 328 dawn of, 318–322 contrast-enhanced, for testicular tumors, 670 Nitze/Leiter, 319 penile cancer, 35 Cytokeratins (CK), 305 prostate cancer, 31 Cytoreductive nephrectomy (CN) renal cell carcinomas, 24, 502–503 active surveillance after, 622–623 retroperitoneal tumors, 763 advantages and disadvantages, 617, 618 testicular cancer, 33 decision-making, 623–627 types, 21 histological factors, 625 Computed tomography (CT) urography IFN-α therapy, 618–619 bladder cancer, 306 IL-2 treatment, 619 urothelial cancer, 25–26 nivolumab, 627, 628 Computerized (C)-TRUS with artificial neural network patient-specific factors, 624 analysis (ANNA), 146–147 vs. presurgical targeted molecular therapy, 627 ConfirmMDx®,115–116 pre-targeted molecular therapy era, 617–619 Conformal three-dimensional radiotherapy (3DCRT), 213 risk stratification tools, 625–626 Congenital mesoblastic nephroma (CMN), 778 surgical considerations, 623 Consolidated Standards of Reporting Trials targeted molecular therapy era, 620–622 (CONSORT), 44 timing of, 626–627 CONSORT, 44 Continent orthotopic urinary diversion clinical evidence, 357 D complications, 367–368 Dacomitinib, 849 follow-up, 366–367 Decipher®, 120–121 patient selection, 365 Denosumab, bone metastases, 78, 83–84 quality of life, 367–368 Denys-Drash syndrome, 775 reservoir compliance, 365 Desperation PC-RPLND, 717 surgical technique, 366 Desperation surgery, 704 Continent urinary diversion Detection bias, 55 ileal pouch, 448 Device-assisted intravesical chemotherapy, 347 orthotopic neobladder, 448 Diabetes mellitus, renal cell carcinomas, 485 Contralateral biopsy, 678–679 Diagnostic biomarkers Contralateral testis, biopsy of, 674 ConfirmMDx®,115–116 Contralateral tumor, history of, 657–658 IsoPSA 245®,114–115 Contrast-enhanced computer tomography, 670 4K Score, 114 Contrast-enhanced ultrasound (CEUS), 21, 24 PHI® and 4K Score, 114 prostate cancer, 148 prostate cancer antigen 3, 116 Corpora amylacea, 163 Prostate Health Index PHI®, 111–113 Cost and convenience bias, 54 SelectMDx®,115 Council for International Organizations of Medical transmembrane protease serine 2:ERG, 116–117 Sciences (CIOMS), 60–61 Differentiated PeIN, 786 C-reactive protein, 521 Digital subtraction angiography, 506 Cryoablation, 562 Distant metastases Cryptorchidism, 658 kidney tumors, follow-up for, 645 CT, see Computed tomography (CT) muscle-invasive bladder cancer, 431–432 CTC, 523 penile cancer, staging assessment for, 813–814 CTLA-4, 524 prostate cancer, 131 CyberKnife radiosurgical treatment, 85 Docetaxel Cyclooxygenase-2 (COX-2), 10 castration-resistant prostate cancer, 245–246 Cyproterone acetate, 259 chemotherapy with, 281–284 Cystectomy mechanism of action, 245 acid-base balance disturbances, 456–457 research activity, 246 bone metabolism after, 459 toxicity management, 246 comparison with, 380 Doppler ultrasound, prostate cancer, 148 early, BCG, 345–346 Double-dummy, in clinical trials, 40 intestinal function disturbances after, 460 Dropout, in clinical trials, 40 856 Index

Dutch/Memorial Sloan-Kettering Cancer Center Everolimus, 609 classification system, 764, 765 External beam radiation therapy (EBRT) Dynamic sentinel lymph node biopsy (DSNB), 810, 811 advances in, 212–214 curative prostate, 212 hypofractionation, 212 E intermediate-risk disease, 216 Early Prostate Cancer Detection Programme localized disease, 214–216 (EPCDP), 102 locally advanced disease, 216–217 Eastern Cooperative Oncology Group (ECOG), 52 low-risk disease, 214–215 Eastern Cooperative Oncology Group Performance Status metastatic setting, 222 (ECOG PS), 624 palliative treatment, 213 E-cadherin, 11 salvage after, 223–224 Elastography, prostate cancer, 147–148 toxicity, 219–220 Elective nodal irradiation (ENI), 213 Extraperitoneal metastases, in lung, 715–716 Electrolyte imbalance, 458–459 Extra-prostatic extension (ECE/SVI), 216 Electromotive intravesical chemotherapy (EMDA), 347 Embryonal carcinoma (EC), 660–661 F Endoscopy Fascin, 521–522 dawn of cystoscope, 318–322 Fatigue developments in, 322–323 ADT, 272 history of, 317 kidney cancer, 501 during nineteenth century, 318 testicular cancer, 724 ureteroscopy, 323–324 Fatty acid synthase (FASN), 170 End-stage renal disease, 485 FDG-PET scan, see 2-Fluoro-deoxy-D-glucose Enzalutamide, 86, 261 (FDG)-PET castration-resistant prostate cancer, 244–245 Fertility, and GCNIS, 680 mechanism of action, 244 18F-fluoro-deoxy-glucose (FDG), 23, 34 research activity, 245 FGFR2, 174 toxicity management, 244–245 Fibroblastic growth factor receptor 3 (FGFR3), 7, 338 Epidermal growth factor (EGF), 11 Field cancerization, 7 Epidermal growth factor receptor (EGFR), 11 Fine-needle biopsy aspiration, 748 Epithelial-mesenchymal transition (EMT), 11 Fixed inguinal lymph nodes, 840 Epithelial-mesenchymal transition (EMT) markers, Fluorescence cystoscopy (photodynamic diagnosis 541–542 (PDD)), 306 Equipoise, principle of, 60 2-Fluoro-deoxy-D-glucose (FDG)-PET Equivalency trial, 40 advanced testicular cancer, 694 Erectile dysfunction (ED), 220 nonseminomatous germ cell cancer, 702 early postoperative phase, 451 PC-RPLND, 708, 709 intracavernous (auto)injection therapy, 452 Fluorodeoxyglucose positron emission tomography medicated urethral system for erection (MUSE), 452 (FDG-PET)-CT, 670 phosphodiesterase-5 inhibitors, 452 Flutamide, 260 treatment options, 450–451 Follicular-stimulating hormone (FSH), 257 vacuum erection device (VED), 452–455 Food and Drug Administration (FDA), 39 Erectile function, nerve-sparing techniques and, 196–198 FOXA1, 173 ERG, 171 Fraud bias, 55 Erythrocyte sedimentation rate (ESR), 521 Full analysis set, in clinical trials, 40 Estrogens, 259 Fumarate hydratase (FH), 8 ETS family, 67, 169, 171 Funding availability bias, 54 ETV1, 171 ETV4, 171 The European Association of (EAU) G guideline, 647 Galeterone, 261 European Medicines Agency (EMA), 39 Gallstones, 487 European Organization for Research and Treatment of Gender, and renal cell carcinomas, 481 Cancer (EORTC), 330, 331, 427–428 Gender bias, 54 European Randomized Study of Screening for Prostate Generalizability, in clinical trials, 40 Cancer (ERSPC) trial, 101, 184 Genetic alteration, 4 European Society of Urogenital Radiology (ESUR), 149 Genetic markers, in prostate cancer, 115–117 Index 857

Genitourinary malignancies Heterotopic continent catheterizable urinary reservoir/ clinical aspects and investigations, 20–35 Mainz pouch I, 364–365 molecular basics on, 3–13 Hidden agenda bias, 54 Genomic Prostate Score (GPS), 117 HIF,8 German PROBASE study, 102 High-intensity focused ultrasound (HIFU), 228, 562–563 Germ cell neoplasia in situ (GCNIS), 660, 677 PSA recurrence after, 230 contralateral biopsy, 678–679 High-risk prostate cancer development of, 678 clinical and biological rationale, 200–201 and fertility, 680 multimodal approach role, 201, 204 pathohistological features, 678 radical prostatectomy vs. radiotherapy, 201 treatment of, 679–680 Histopathological assessment, prostate cancer Germ cell tumor of the testis (GCT) acinar adenocarcinoma, 162–164 cisplatin-based chemotherapy, 656 atypical small acinar proliferation (ASAP), 166–167 contralateral tumor, history of, 657–658 classification, 160 cryptorchidism, 658 cytological features, 160–162 death rates, 656 diagnosis method, 160 genetic predisposition, 658 grading, 164–165 height, 658 immunohistochemistry, 168–170 histopathology, 659–663 macroscopy, 160 infertility, 658 molecular signatures, of primary and metastatic, 170–174 microlithiasis, 658 needle biopsies, 165 mortality rates, 657 prostatic intraepithelial lesion (PIN), 166 risk factors for, 655–659 radical prostatectomy specimen, 165–166 survival rates, 657 treatment effects, 164 WHO classification, 659–660 Hitachi real-time virtual sonography, 152 worldwide incidence, 656, 657 Hormonal treatment mechanism, 257 Giant cell urothelial carcinomas, 417 Hot flushes, 270–271 Glansectomy, 825–827 Hounsfield unit (HU) scale, 21 Glans resurfacing technique, 822–824 HOXB13,4 Gleason score, 164, 165 Human Development Index (HDI), bladder cancer, 296 GLUT3, 12 Human papillomavirus (HPV) Glutathione-S-transferase P1 (GSTP1),115 in PeCa carcinogenesis, 9–10 Gonadotropin-releasing hormone (GnRH) antagonists, in PeIN, 786 257–259 in squamous cell carcinoma, 803 Granulosa cell tumors, 664 basaloid SCC, 790 GSTP1 (glutathione-S-transferase P1), 115 clear cell carcinoma, 791–792 Guideline-based ablation procedures, 560–561 lymphoepithelioma-like carcinoma, 792 Gynecomastia, 271–272 papillary basaloid carcinoma, 790 warty-basaloid carcinoma, 791 warty carcinoma, 790–791 H Hypercalcemia, 78 Hand-assisted partial nephrectomy (HALPN), 584 Hypernephromas, 479 Hand-assisted technique (HALN), 583 Hypertension Heidenreich criteria, 703 prostate cancer, 243, 263 Hematuria renal cell carcinomas, 484–485 bladder cancer, 297, 328 Hypoxia-inducible factor (HIF-α) degradation, 519 urothelial cancer, 25 Hysterectomy status, 488 HER2,62 Hereditary disorders, with renal cell carcinomas, 490–492 I Hereditary leiomyomatosis and associated renal cell IFN-α carcinoma (hlRCC) BCG with, 345 clinical features, 491 IGF-1, 523 definition, 545 IL-6, 524 histopathology, 546 Ileal conduit, 364 immunohistochemistry, 546 Ileus, intestinal hypomotility and paralytic, 460 macroscopy, 545 Image-guided radiotherapy (IGRT), 213 molecular pathology, 546 Imaging, see Radiology Hereditary papillary renal carcinoma, 8, 491 Immune checkpoint inhibitors, 617 858 Index

Immune-mediating proteins, 542 Investigational new drug (IND) application, 39 Immune system markers Irreversible electroporation (IRE), 563 B7-H1, 524 Isolated high-grade PIN (HGPIN), 166 CTLA-4, 524 Isolated inguinal lymph node recurrence IL-6, 524 chemotherapy, 802 natural killer cells (NK Cells), 524 recommendations for, 802–803 PD-1, 525 salvage radiation, 802 PD-L, 525 surgical management, 802 regulatory T cells (Treg), 524 IsoPSA 245®,114–115 tumor-infiltrating lymphocytes (TILs), 524 iSR’obotTM Mona Lisa, 152–153 Immunosuppression with organ transplantation, 486 – In-bore biopsy, prostate cancer, 149 150 K Incontinence treatment, change in lifestyle, 448 4 kallikerin (4 K) score, 28 Independent data monitoring committee (IDMC), 40, 59 Kallikreins, 5 Inguinal lymph node dissection, 798 Ketoconazole, 261 Inguinal orchiectomy, 673–674 Ki-67, 10, 11, 521 Institutional review board bias, 54, 59 Kidney cancers Insulin-like growth factor 2 (IGF-II) gene, 746 characteristics, 580 Insulin-like growth factor II mRNA-binding protein molecular basics, 8–9 3 (IMP3), 521 symptoms and diagnosis, 499–510 Intensity-modulated radiotherapy (IMRT), 213 See also Kidney tumors, follow-up for Intention-to-treat (ITT) principle, 40, 48 Kidney stones, 459, 487 Interim analysis, in clinical trials, 40 Kidney surgery Intermediate Clinical Endpoints in Cancer of the Prostate guidelines of, 570 (ICECaP), 51 surgical management, 576 Intermittent androgen deprivation therapy (IAD), 262 Kidney tumors, follow-up for International Index of Erectile Function (IIEF) aspects of, 642 questionnaire, 195 cost-effectiveness ratio, 648 International Metastatic RCC Database Consortium evidence-based suggestions, 648–651 (IMDC) score, 599 functional surveillance, 643 Inter-rater reliability, 40 guideline recommendations for, 647 Intervention choice bias, 54 length of, 647–648 Intestinal function disturbances, 460 oncological outcomes, surveillance for, 643–645 Intestinal function disturbances, after cystectomy prognostic models and nomograms, 645–647 intestinal hypomotility and paralytic ileus, 460 rationale for, 642–643 mucous formation within intestinal reservoirs, 460 KIT gene, 12 osmolarity equilibrium, intestinal urinary reservoirs, Klippel-Trénaunay-Weber syndrome, 775 460–461 KLK3,5 short bowel syndrome, 460 KRAS gene, 12 Intracavernous (auto)injection therapy, 452 KRAS/NRAS mutations, 12 Intracavitary chemotherapeutic agents, 346 4K Score, 114 Intradermal priming, 345 Intra-rater reliability, 40 Intratumoral heterogeneity (ITH), 66 L cytogenetic, 531 Lactate dehydrogenase (LDH), 33, 522, 669, 727 functional, 530–531 Language bias, 55 genomic, 531 Laparoscopic partial nephrectomy (LPN), 583–584 molecular, 532–533 clinical performance, 585–586 multiregion genomic, 531–532 oncological outcome, 586 mutational, 531 Laparoscopic radical nephrectomy outlook and clinical implications, 534 clinical performance, 584–585 RCC with sarcomatoid differentiation, 532 oncological outcome, 586 spatial, 533–534 Laparoscopic renal surgery temporal heterogeneity and evolution, 533 patient selection and indications, 581–582 Intravenous urography (IVU), 20 surgical techniques, 582–583 bladder cancer, 328 Laser ablation, 821–822 Intravesical chemotherapy, 331–332 LDH, see Lactate dehydrogenase (LDH) Intravesical immunotherapy, 332 Leibovich score, 646, 647 Invasive tumor therapy, 455 Lenvatinib, 608 Index 859

Leydig cell tumors, 663 renal cell carcinomas, 24–25, 503–505 Lichtleiter, 318 T1 and T2 images, 29 Life expectancy, prostate cancer, 99 testicular cancer, 33, 670 Liver metastases, 703, 716 types, 22 Long-term androgen deprivation therapy uses, 22 (LTADT), 216 Malabsorption and malnutrition Lower urinary tract symptoms (LUTS), 27 altered pharmacokinetics, 459 Lugano classification, 697 bone metabolism after cystectomy, 459 Lung metastases, 630–631 electrolyte imbalance, 458–459 Luteinizing-hormone-releasing hormone (LHRH) postoperative catabolic phase, 457–458 agonists, 257, 258, 278 prevalence, 457 analogues, 281, 284 renal function and stone formation after antagonists, 257, 258, 278 cystectomy, 459 Lymphadenectomy (LND), 623 vitamin B12 deficiency, 458 Lymphatic flow disturbance after pelvic lymphadenectomy vitamin D deficiency, 458 compression bandages, 462 Malignant pheocromocytoma device-assisted lymphatic drainage with intermittent biochemical evaluation, 751 negative pressure, 461–462 clinical presentation, 750–751 device-assisted lymphatic drainage with positive CT scan, 751 pressure, 461 epidemiology, 750 home exercises for lymphatic drainage, 462–463 18F-DOPA PET/CT, 751 lymphoedema, pelvic lymphadenectomy, 461 fludeoxyglucose-positron emission tomography, 751 manual lymph drainage, 461 imaging studies, 751 Lymphatic spread, in penile cancer, 834–835 iodine-123 MIBG, 751 Lymph node metastases, in penile cancer laparoscopic approach, 752 clinical approach for, 839–840 management, 752 diagnosis of, 836–837 medical therapy, 752 histopathological parameter, 835–836 radiotherapy, 752 incidence of, 835 surgical intervention, 752 inguinal lymph node disease, 835 Mammalian target of rapamycin (mTOR) management strategies, 837–839 inhibitors, 617 modified inguinal lymphadenectomy, 838 Matrix metalloproteinase (MMP), 11, 520–521 molecular parameters, 836 Maximum androgen blockade (MAB), 262 pelvic lymphadenectomy, 838–839 Maximum tolerated dose (MTD), 43 prognostic factors, 835–836 MCNA, 345 radical inguinal lymphadenectomy, 838 Medical rehabilitation robotic-assisted inguinal lymphadenectomy, 838 cystectomy and urinary diversion, metabolic sentinel node biopsy, 837–838 changes, 456 surgical lymph node staging, 837 intestinal function disturbances after cystectomy, 460 surgical morbidity, 839 lymphatic flow disturbance after pelvic surveillance strategies, 837 lymphadenectomy, 461 video endoscopic lymphadenectomy, 838 sexual function disturbances, 450 Lymph node staging, prostate cancer, 129–131 urethral anastomosis complications, 463–464 Lymphoepithelioma-like carcinoma, 792 urinary incontinence, 440 Lymphoepithelioma-like urothelial carcinomas, urinary tract infection after cystectomy, 455–456 418–419 Medicated urethral system for erection (MUSE), 452 Memorial Sloan Kettering Cancer Center (MSKCC) M score, 599 Magnetic resonance imaging (MRI) Meta-analysis (MA), in clinical trials, 40 adrenocortical carcinoma, 748 Metachronous testicular tumor, 724 advanced penile SCC, 797 Metals exposure, renal cell carcinomas, 489 bone metastases with prostate cancer, 81 Metastasectomy, for mRCC dynamic contrast enhancement, 29 adrenal metastases, 631–632 penile cancer, 35 aim of, 628 principle, 22 atypical metastases, 632 prostate cancer, 29–31 bony metastases, 631 bone staging, 131–132 brain metastases, 631 lymph node staging, 129–130 complications, 632 MRI and ultrasound fusion, 150–153 lung metastases, 630–631 860 Index

Metastasectomy (cont.) Morbidity pancreatic metastases, 632 chronic urinary, 221 single/multicenter retrospective outcomes, 628–630 prostate cancer, 99–101 systemic therapy, 634 mRCC, see Metastatic renal cell carcinoma (mRCC) Metastatic bladder cancer disease MRE11 expression, 375 carboplatin-combination chemotherapy, 407 MRI, see Magnetic resonance imaging (MRI) chemotherapy, 408 MR urography, 25, 27 cisplatin-combination chemotherapy, 404–407 MSMB,5 clinical prognostic factors, 404 Mucinous tubular and spindle cell carcinoma (mtsRCC) combinations with targeted therapies, 407–408 definition, 548 first-line treatment, 404–408 histopathology, 549 immunotherapy, 408–409 immunohistochemistry, 549 non-platinum combination chemotherapy, 407 macroscopy, 548 post-chemotherapy surgery, 409 molecular pathology, 549 second-line treatment, 408–409 Mucous formation within intestinal reservoirs, 460 Metastatic hormone-naive prostate cancer (mhPCA) Multicenter trial, 40 local treatment of primary, 279–281 Multidetector-row CT (MDCT), 328 systemic treatment, 281–286 Multilocular cystic renal neoplasm, 544 Metastatic renal cell carcinoma (mRCC), 615 Multimodal continence training chemoresistance, 616 biofeedback training, 442–445 cytokines, 600–602 electroneurostimulation, 445–447 cytoreductive nephrectomy, 617–628 innovative approaches, 447 immunotherapy, 608–609 personal biofeedback, physiotherapy, 443–444 medical treatment, 599–600 qualified, 442 metastasectomy, 628–635 training under everyday conditions, 444 monoclonal antibodies, 605–606 Multiparametric MRI (mpMRI), 127–128, 133 mTOR inhibitors, 604, 606 prostate cancer, 148–149 prognostic scores, 599 Muscle-invasive bladder cancer (MIBC) progression-free survival, 596 cardiovascular aspects, 472 quality of life, 609 characteristics, 424 radiotherapy, 632–634 cT-Stage, 431 recommendations, 610 diagnositic tools, 305 second line treatment, 606–609 distant metastases (M-Stage), 431–432 systemic treatment, 599–604 distant recurrences, 471 targeted agents, 610 follow-up, functional outcomes and complications, targeted therapies, 602–604 471–472 treatment options, 600–602 follow-up scheme, 473 tyrosine kinase inhibitors, 604–608 local recurrence, 470–471 VEGF-targeting agents, 603 lymph node metastases (cN-Stage), 431–432 MET gene, 8 predictive molecular markers, 433 Microcystic urothelial carcinomas, 417 prognostic and predictive clinical factors, 432 Microlithiasis, 658 prognostic molecular markers, 433 Micropapillary carcinomas, 415–416 MYC,5 Microphthalmia-associated transcription factor MYCN, 174 (MiT), 494 β-Microseminoprotein expression, 5 Microwave ablation (MWA), 563–564 N Microwave-induced hyperthermia (MIH), 347 Narrow band imaging (NBI) Minimally invasive radical prostatectomy bladder cancer, 306 history and epidemiological data, 199–200 TURBT, 313–314 oncological and functional outcomes, 200 Natural killer cells (NK Cells), 524 miRNA, 371, 523–524, 726–727 NCOA2, 172 MiT family translocation renal cell carcinomas, 550 Neoadjuvant chemotherapy Mitotane, 749, 750 vs. adjuvant, 398 Mixed squamous cell carcinoma, 790 advanced penile SCC, 799–800 Modified inguinal lymphadenectomy, 838 biomarkers for patient selection, 387, 390 Moh’s micrographic surgery, 819, 824 chemotherapy regimens comparison, 391–392 Molecular biomarkers, 517 clinical trials and meta-analyses testing, 388–389 prostate cancer, 117 contemporary retrospective evidence, 387 Index 861

long-term oncological outcomes, 386–387 intravesical immunotherapy, 332 oncological outcomes, 385 low-risk, 470 randomized controlled trials, meta-analyses, 385–386 molecular markers, 429 rationale, 384–385 molecular markers, recurrence prediction, 430 surgical outcomes after, 390–391 physical examination, 328 toxicity associated with delivery, 390 prevalence, 425 Nephrectomy prognosticators and risk nomograms, 427–428 high-risk RCC after, 649 recurrence rate, 429–430 intermediate-risk RCC after, 649 TNM classification and CIS, 425–427 low-risk RCC after, 648 transurethral resection, 330 Nephroblastoma, see Wilms tumor (WT) TUR, 425 Nephron-sparing surgery (NSS), 779 ultrasound, 328 Nerve-sparing radical cystectomy urinary cytology, 329 clinical evidence, 357 urinary marker tests, 329–330 safety and technique, 358 Nonpalpable inguinal lymph nodes, 839–840 Nerve-sparing techniques Non-platinum combination chemotherapy, 407 anatomical background, 196 Non-seminoma clinical stage II A/B treatment, 692–693 and erectile function, 196–198 Nonseminomatous germ cell cancer (NSGCC), 702–703 and oncological safety, 198–199 PEB application schemes, 698 and urinary continence, 198 residual tumor resection, 702–703 Nested-type/large nested urothelial carcinomas, 416–417 standard chemotherapy regime, 698, 699 Neutrophils, 522 Non-seminomatous germ cell tumors (NSGCT) New drug application (NDA), 39 advanced, PC-RPLND, 710–712 NGAL, 523 choriocarcinoma, 663 Nitze Kystoskop, 321 embryonal carcinoma, 660–661 Nitze/Leiter cystoscope, 319 teratoma, 663 Nivolumab, 608–609, 617, 627, 628 yolk sac tumor, 661, 663 Nocturnal urinary incontinence, in orthotopic Nonsteroidal antiandrogens, 259 neobladder, 449 Normal inguinal lymph nodes, 810–811 Nonalcoholic beverage consumption, renal cell NSGCC, see Nonseminomatous germ cell cancer carcinomas, 483 (NSGCC) Non-germ cell tumors, 663–664 NSGCT, see Non-seminomatous germ cell tumors Non-HPV-related PeIN, 786 (NSGCT) Non-HPV-related squamous cell carcinoma N-telopeptide (NTx), 81–82 adenosquamous carcinoma, 790 carcinoma cuniculatum, 789 O mixed SCC, 790 Obesity, renal cell carcinomas, 484 papillary carcinoma NOS, 789–790 Oncocytic papillary renal cell carcinoma (opRCC), pseudoglandular carcinoma, 788–789 544–545 pseudohyperplastic carcinoma, 788 Oncocytoma, 493–494 sarcomatoid SCC, 790 Oncogenes, 4 SCC usual type/NOS, 787–788 OncotypeDX Genomic Prostate Score®, 117, 119 verrucous carcinoma, 789 Open partial nephrectomy (OPN) Non-inferiority trial, 40 indications, 580 Nonmetastatic failure management, 232 patient selection, 580 Nonmetastatic prostate cancer, 263 Open radical nephrectomy (ORN) Non-muscle-invasive bladder cancer (NMIBC) indications, 580 BCG failure and early cystectomy, 332 patient selection, 580 characteristics, 424 Orchiectomy, 278 clinical symptoms, 328 bilateral, 258 computed tomography (CT) imaging, 425 Orteronel, 260–261 cystoscopy, 329–330, 425 Osmolarity equilibrium, intestinal urinary reservoirs, diagnosis, 328 460–461 diagnositic tools, 305 Outcome choice bias, 55 follow-up scheme, 470, 473 high-risk, 470 P histological WHO grade, 427 Palpable inguinal nodes, 811–813 imaging, 328–329 Palpable lymph nodes, 840 intravesical chemotherapy, 331–332 Pancreatic metastases, 632 862 Index

Papillary basaloid carcinoma, 790 lymph node management, 833–841 Papillary carcinoma NOS, 789–790 metastatic development, 11 Papillary renal cell carcinoma (pRCC), 493 molecular basics, 9–11 definition, 544 MRI, 35 histopathology, 544–545 normal inguinal lymph nodes, 810–811 immunohistochemistry, 544–545 palpable inguinal nodes, 811–813 macroscopy, 544 pelvic nodes, ipsilateral surgical staging of, 813 molecular pathology, 544–545 PET/PET-CT, 35 type 1, 508–510 premalignant lesions, 34 Papillomatous tumor of bladder, 324 primary tumor diagnosis, 808–810 Paraganglioma syndromes, 492 recurrence, diagnosis of, 814 Partial glansectomy, 825 regional lymph nodes, diagnostic and staging Partial nephrectomy, 565 algorithm for, 813 high-risk RCC after, 649, 651 risk factors, 10 intermediate risk after, 651 tumor progression, 11 local recurrence in kidney, 644 Penile carcinoma low-risk RCC after, 649 epidemiology, 785–786 Partial , 827–829 histopathology, 786–792 Partial vs. total nephrectomy malignant epithelial tumors, 787–792 for complex renal mass, 573–575 penile intraepithelial neoplasia, 786–787 decision-making process, 575–576 risk factors, 785 in elderly, 575 See also Advanced penile squamous cell carcinoma for small renal mass, 572–573 Penile intraepithelial neoplasia (PeIN), 786–787 trends in, 571 Penile-preserving surgery Patient-Reported Outcomes Measurement Information circumcision, 824 System (PROMIS), 104 Glans resurfacing technique, 822–824 Pazopanib, 604 laser ablation, 821–822 PCA3, 104 lesions confined to prepuce, 824 PCNA, 11 lesions extending into corpus cavernosa, PC-RPLND, see Postchemotherapy retroperitoneal lymph 827–829 node dissection (PC-RPLND) lesions extending to corpus spongiosis/distal PD-1, 525 urethra, 825–827 PD-L, 525 Moh’s micrographic surgery, 819, 824 Pelvic lymphadenectomy, 838–839 recurrence rate, 819–820 lymphatic flow disturbance after, 461 sexual function, importance of, 820 lymphoceles after, 463 surgical resection margins, 818–819 lymphoedema following, 461–463 Penile squamous cell carcinoma Pelvic lymph node dissection (PLND) adjuvant chemotherapy, 847–848 advanced penile SCC, 798 afatinib, 849 extent of, 204, 361–363 chemoradiation approach, 848–849 limited and extended templates, 205 dacomitinib, 849 lymph node staging, 204–205 disease course of, 846 necessity of, 361 immune checkpoint inhibitors, 849 oncological outcomes, 205–206 neoadjuvant chemotherapy, 847 radical cystectomy with, 352 pembrolizumab, 849 as staging procedure, 361 perioperative treatments, 846–847 Pembrolizumab, 849 Percutaneous radiotherapy, 564 Penile cancer Performance bias, 55 bulky inguinal lymph nodes, 812, 813 Per protocol (PP) set, 40 carcinogenesis, 9–10 PET, see Positron emission tomography (PET) clinical aspects, 34 PET-CT clinical presentation, 34 bone metastases with prostate cancer, 81 CT scan, 35 lymph node metastases, 836 distant metastases, staging assessment for, renal cell carcinomas, 505–506 813–814 Petroleum products exposure, renal cell carcinomas, 489 histological diagnosis, 35 P53 gene, 7 imaging, 35 Pharmacokinetics, altered, 459 invasive cancer, 34 PHI® and 4K Score, 114 laboratory investigations, 34–35 Phosphodiesterase-5 inhibitors, 452 Index 863

Photodynamic diagnosis (PDD), 330 PROBASE study, 102, 105 BCG, 347 Prognostic biomarker bladder cancer, 306 Decipher®, 120–121 TURBT, 313–314 OncotypeDX Genomic Prostate Score®, 117, 119 Physical activity, renal cell carcinomas, 483–484 Prolaris®,119–120 Placental-like alkaline phosphatase (PLAP), 678 ProMark®, 120 Plasmacytoid urothelial carcinomas, 414–415 Prolaris®,119–120 Platelet-derived growth factor (PDGF), 8 ProMark®, 120 Platinum-based chemotherapy, 472 PROMIS study, 104 PLCO trial, 101 Prostate cancer Polycystic kidney disease, 485–486 AU-ESTRO-SIOG guidelines, 229 Population or sample choice bias, 54 biomarkers, 28 Positron emission tomography (PET) biopsy adrenocortical carcinoma, 748 antibiotic management, 154–155 with computed tomography, for advanced penile SCC, complications, 153–154 797–798 indications and future perspective, 155–156 penile cancer, 35 targeted biopsy, 146–153 prostate cancer, 31 ultrasound-guided, 142–146 biochemical and clinical recurrence staging, 133–137 bone metastases with, 79–86 bone staging, 132 bone scan, 31 local staging, 128–129 bone staging, 131–137 lymph node staging, 130–131 clinical aspects, 27 testicular cancer, 34 clinical presentation, 27 types, 23 clinical states model, 64 Postchemotherapy retroperitoneal lymph node dissection CT scan, 31 (PC-RPLND), 719 diagnostic biomarker, 111–117 adjunctive surgery, 717–718 diagnostic tools, 102–105 in advanced NSGCT, 710–712 distant metastasis, 131 in advanced , 709–710 epidemiology, 98 after salvage chemotherapy, 716–718 first-line hormonal treatment, 267–268 anatomical extent of, 714 high-risk, 201–203 bone metastases, 716 histopathological assessment brain metastases, 716 acinar adenocarcinoma, 162–164 complications, 718 atypical small acinar proliferation (ASAP), consolidation chemotherapy, 718 166–167 desperation, 717 classification, 160 FDG-PET scan, 708–710 cytological features, 160–162 indications for, 718 diagnosis method, 160 intraoperative frozen section analysis, 714 grading, 164–165 liver metastases, 716 immunohistochemistry, 168–170 modified, 714, 715 macroscopy, 160 nonseminomatous germ cell tumors, 708 molecular signatures, of primary and metastatic, nonseminomatous testicular germ cell tumors, 708 170–174 timing of, 712–713 needle biopsies, 165 Postoperative catabolic phase, 457–458 prostatic intraepithelial lesion (PIN), 166 Postpubertal teratoma, 663 radical prostatectomy specimen, 165–166 p53 protein, 520 treatment effects, 164 Prednisone, 284–285 imaging, 29 Prepubertal teratoma, 663 initial staging, 126–127 Primary kidney tumor biopsy, 506–508 life expectancy, 99 Primary radiotherapy of lymph nodes, 801 local staging, 126–129 Primary retroperitoneal lymph node dissection (RPLND), lymph node staging, 129–131 692, 693 metastatic hormone-naive (see Metastatic hormone- Primary urethral carcinoma (PUC) naive prostate cancer (mhPCA)) definition, 738 molecular basics, 4–5 etiology and risk factors, 738 morbidity, 99–101 follow-up, 742–743 MRI, 29–31 incidence, 738 natural history of untreated localized treatment of, 741–742 from active surveillance case series, 187–188 864 Index

Prostate cancer (cont.) Q healthy men, 182–184 Quality of life (QoL), in mRCC, 609 historical background, 180–181 QUANTEC organ-at-risk dose recommendations, 219 population-based case series data, 181–182 Prostate Cancer Intervention Versus Observation Trial (PIVOT), 186 R from prostate-specific antigen screening trials, Race and ethnicity, renal cell carcinomas, 481–482 184–185 Radiation Prostate Testing for Cancer and Treatment Trial induced sarcoma, 765 (ProtecT), 186–187 renal cell carcinomas, 489–490 Scandinavian Prostate Cancer Group 4 Trial Radiation therapy (SPCG-4), 185 advanced penile SCC, 801 positron emission tomography, 31 BCG, 347 prevalence, 278 bone metastases, 84 prognostic biomarker, 117–120 retroperitoneal tumors, 767–769 prostate-specific antigen, 27–28 Wilms tumor, 780 17q21–17q22 region study, 4–5 Radical cystectomy (RC) 8q24 region study, 5 complications after, 356 recurrence, 228 conditional survival after, 355–356 recurrence, oligometastatic management, 237 local recurrence and quality of surgery, 355 screening, 101–102, 105 lymph node metastases patients with, 354–355 ultrasound, 29 nerve-sparing, 357–358 Prostate cancer antigen, 64 oncologic outcomes, 353, 354 Prostate cancer antigen 3, 116 open, 354 Prostate cancer gene 3 (PCA 3), 28 perioperative mortality after, 356 Prostate Cancer Intervention versus Observation Trial preoperative assessment, 353 (PIVOT), 186 robot-assisted, 358–360 radical prostatectomy, 193 standardized reporting, 356 Prostate Cancer Working Group 3 (PCWG3), 64, 71 survival probabilities after, 353–354 Prostate health index (PHI), 28, 111–113 Radical inguinal lymphadenectomy, 838 Prostate Imaging Reporting and Data System Radical prostatectomy (RP) (PIRADS), 149 clinical and biological rationale, 200–201 Prostate, Lung, Colon, and Ovary (PLCO) continence, 195–196 trial, 184 functional outcomes after, 194–199 Prostate-specific antigen (PSA), 5, 27–28, 98 lymph node metastases detection, 205 optimal treatment, 228 lymph node staging, 204–205 recurrence, 228 minimally invasive, 199–200 rising, 228 multimodal approach role, 201, 204 testing, 192 nonmetastatic failure management following, 232 Prostate-specific membrane antigen (PSMA), 23, patient selection, 194 132–137 pelvic lymph node dissection, 204 Prostate Testing for Cancer and Treatment Trial potency and sexuality, 194–195 (ProtecT), 186–187 Prostate Cancer Intervention versus Observation Trial Prostatic intraepithelial lesion (PIN), 166 (PIVOT), 193 Protein-based marker systems, 305 vs. radiotherapy, 201 Proton beam therapy, 214 recurrence, 228 Proto-oncogenes, 4 salvage after, 224 PSA, 133–136 Scandinavian Prostate Cancer Group Study Number Pseudoglandular carcinoma, 788–789 4 (SPCG-4), 192–193 Pseudohyperplastic carcinoma, 788 SPCG-4 vs. PIVOT, 193–194 PSMA, see Prostate-specific membrane antigen vs. watchful waiting, 192–194 (PSMA) Radical urological tumor interventions Psychological rehabilitation, 464 consequences, 438 pT2, 166 rehabilitation (see Rehabilitation) PTEN, 170, 172 Radiofrequency ablation (RFA), 561 pT2/pT3 penile cancer, 837 Radiology Publication bias, 55 bone scans, 22 PUC, see Primary urethral carcinoma (PUC) computed tomography, 21 Pulmonary metastases, 703 intravenous urography, 20 Index 865

magnetic resonance imaging, 22 bone metastases with, 88–89 PET scans, 23 bone scintigraphy, 506 ultrasound, 21 CAF, 523 X-ray, 20 CAIX, 522 Radiopharmaceuticals, bone metastases, 85 cancer genome atlas, 492–493 Radiotherapy carbonic anhydrase IX, 541 adrenocortical carcinoma, 749 caveolin-1, 521 in mRCC, 632 CEC, 523 abscopal effect, 633 cell adhesion proteins, 541 efficacy, 633 cell cycle proteins, 541 local recurrence, 633–634 CEP, 523 stereotactic body radiotherapy, 632, 633 cfDNA levels, 523 radical prostatectomy vs., 201 characteristics, 479, 538 Radium-223, 86 chemotherapy exposure as child, 488 Radium223 dichloride, 246 chest X-ray, 506 RAF, 174 chromophobe, 493, 546–547 Randomized controlled trials (RCT), 38, 39 chronic hepatitis C infection, 487 designs, 41, 45 chronic kidney disease, 485 ethical foundation, 60 cigarette smoking, 482–483 obstacles, 67–70 classification, 539 randomization, 56–57 clear cell, 492–493, 542–544 sample size estimation, 47 clinical aspects, 23 statistical analysis, 48 clinical conditions, 484–487 RANKL pathway, 79–80 clinical outcome disparities, 482 Rapamycin, mechanistic target, 520 clinical outcomes, 495 RASSF1,115 coal exposure, 489 RB1, 173 collecting duct carcinoma, 494, 548 RB gene, 7 computed tomography, 24 Receptor activator of NF-κB ligand (RANKL), C-reactive protein, 521 79–80 CT, 502–503 RECIST criteria, 70–71 CTC, 523 Rectosigmoid bladder/Mainz pouch II, 364 diabetes mellitus, 485 Redo-RLAs, 704 diagnostic tools, 501 Regional lymph nodes, 126, 127, 813 digital subtraction angiography, 506 Regulation bias, 54 end-stage renal disease, 485 Regulatory T cells (Treg), 524 epithelial-mesenchymal transition (EMT) markers, Rehabilitation 541–542 goals after invasive tumor interventions, 439 erythrocyte sedimentation rate (ESR), 521 medical (see Medical rehabilitation) excess body weight and obesity, 484 psychological, 464 family history, 490 social counseling and professional, 464 fascin, 521–522 structural requirements for centers, 439 gallstones, 487 Renal angiomyolipomas (AML), 24 gender, 481 Renal cell carcinoma (RCC) grading, 539–540 advanced hereditary disorders, 490–492 adjuvant therapy, 598–599 hereditary leiomyomatosis, 491, 545–546 histology, 597–598 hereditary papillary renal cancer (HPRC), 491 surgical treatment, 597 histological classification, 542 age and gender, 481 history, 501 alcoholic consumption, 483 hypertension, 484–485 analgesics, 488 hysterectomy status, 488 anaplastic lymphoma kinase gene (ALK), 495 IGF-1, 523 angiomyolipoma, 510 imaging, 24, 502 appearance, 24 immune-mediating proteins, 542 autoimmune diseases, 486 immunosuppression with organ transplantation, 486 BAP1 mutations, 492 incidence, 481 biological pathways and markers in, 518 incidence of, 616 Birt-Hogg-Dubé disease (BHD), 491 insulin-like growth factor II mRNA-binding protein blood-based biomarkers, 522 3 (IMP3), 521 866 Index

Renal cell carcinoma (RCC) (cont.) systemic therapy for, 616, 617 intratumoral heterogeneity (ITH) (see Intratumoral thrombocytosis, 522 heterogeneity (ITH) tissue-based biomarkers, 517–520 Ki-67, 521 TNM classification and staging, 507–508 kidney stones, 487 translocation carcinomas, 494 laboratory, 502 trichloroethylene exposure, 488–489 laboratory investigations, 23–24 tuberous sclerosis complex (TSC), 492 LDH, 522 tubulocystic, 547–548 lifestyle factors, 482–484 tumor necrosis, 521 matrix metalloproteinase (MMP), 520–521 ultrasound, 24, 502 medications and medical therapies, 488 urinary tract infections, 486–487 metals exposure, 489 use of biomarkers, 521 metastatic (see Metastatic renal cell carcinoma vascular endothelial growth factor, 541 (mRCC)) vascular endothelial growth factor receptor, 596–597 miRNAs, 523–524 VEGF, 522 MiT family translocation, 550 vimentin, 521 molecular basics, 8–9 Von Hippel-Lindau syndrome, 490–491 molecular biomarkers, 517 See also Advanced renal cell carcinoma mortality, 481 Renal cystic lesions, 509 MRI, 24–25, 503–505 Renal function and stone formation, 459 mucinous tubular and spindle cell carcinoma, 548–549 Renal medullary carcinoma (RMC), 486, 494, 550–551 multilocular cystic renal neoplasm, 544 Renal surgery neutrophils, 522 laparoscopic, 581–586 NGAL, 523 open, 580–581 nomenclature, 539 OPN vs. LPN, 588 nonalcoholic beverage consumption, 483 ORN vs. LRN, 587 occupational and environmental exposures, 488–490 RN vs. PN, 587–588 oncocytoma, 493–494 robotic, 586–587 overall survival and/or progression-free survival, transperitoneal approach, 582 513–517 Renal tumor enucleation, 565 papillary, 493, 544–545 Response Evaluation Criteria In Solid Tumors (RECIST), papillary RCC type 1, 508–510 70–71 paraganglioma syndromes, 492 Retroperitoneal LRN, 583 PET-CT, 505–506 Retroperitoneal lymphadenectomy (RLA), 686 petroleum products exposure, 489 Retroperitoneal sarcomas (RPS), 761–763 physical activity, 483–484 See also Retroperitoneal tumors physical examination, 502 Retroperitoneal tumors polycystic kidney disease, 485–486 AJCC/UICC system, 764, 765 p53 protein, 520 benign and malignant primary retroperitoneal tumors, pregnancies numbers, 487–488 760, 761 prevalence, 479 chemotherapy, 769 primary kidney tumor biopsy, 506–508 clinical presentation and diagnosis, 763–764 prognosis, 616 computed tomography, 763 prognostic markers, 512–513, 540 epidemiology and classification, 760–763 race and ethnicity, 481–482 histological characterization, 764 radiation, 489–490 intraoperative radiation, 768 rapamycin, mechanistic target, 520 postoperative radiation, 768–769 renal medullary carcinoma, 550–551 preoperative radiation, 767–768 renal medullary carcinoma (RMC), 494 radiation therapy, 767–769 reproductive and hormonal factors, 487–488 recurrence and follow-up, 769–770 risk factors for, 616 risk factors and prognosis, 764–766 SAA, 522–523 surgical resection with negative surgical margins, sarcomatoid tumors, 494–495 766–767 sickle cell disease, 486 Retroperitoneum, defined, 760 staging, 539 Robot-assisted radical cystectomy (RARC), 352 subtypes, 542–551 challenges ahead, 360 succinate dehydrogenase-deficient, 549–550 characteristics, 358–359 survivin, 520 complications after, 359 symptomatology, 500–501 oncologic outcomes after, 359–360 Index 867

Robotic-assisted inguinal lymphadenectomy, 838 partial vs. total nephrectomy, 572–573 Robotic renal surgery, 586–587 percutaneous radiotherapy, 564 RTOG-EORTC radiation toxicity scoring criteria, 218 radiofrequency ablation (RFA), 561 renal tumor enucleation, 565 surgery, 565 S watchful waiting, 560 SAA, 522–523 Social counseling and professional rehabilitation, 464 Safety, in clinical trials, 41 Social medical assessment, 464–466 Salvage brachytherapy, 223, 235 Sorafenib, 605, 607 Salvage cryosurgical ablation of the prostate (SCAP), Sotos and Perlman syndrome, 775 235–236 SPOP, 173 Salvage HIFU Ablation, 236 Squamous cell carcinoma (SCC) Salvage lymph node dissection (SLND), 236 bladder cancer, 296 Salvage radiation therapy (SRT), 232–234 needle biopsy, 163 advanced penile SCC, 802 See also Advanced penile squamous cell carcinoma Salvage radical prostatectomy (SRP), 234–235 Stage III germ cell cancer, 697–700 Sarcomatoid squamous cell carcinoma, 790 Stage T1 bladder cancer Sarcomatoid tumors, 494–495 diagnosis, 328–330 Sarcomatoid urothelial carcinomas, 418–419 treatment, 330–332 Saturation biopsy, prostate cancer, 145–146 Statistical analysis plan (SAP), 41 Scandinavian Prostate Cancer Group 4 Trial (SPCG-4), Stereotactic body radiotherapy (SBRT), 214, 222–223, 185, 192–193 632, 633 Secondary urethral carcinoma (SUC) Steroidal antiandrogens, 259 definition, 738 STHLM3 model, 102 etiology and risk factors, 738 Stoma care, 449–450 follow-up, 742–743 Stone formation, renal function and, 459 urethral-sparing treatment, 742 Stress incontinence, insufficient pelvic floor, 442 urethrectomy for, 742 SUC, see Secondary urethral carcinoma (SUC) Selection bias, 53 Succinate dehydrogenase-deficient, 549–550 Selective reporting bias, 55 Succinate dehydrogenase-deficient renal cell carci nomas SelectMDx®,115 (sdhRCCs), 549–550 Self-fulfilling prophecy bias, 54 Sunitinib, 604–605, 607 Seminoma, 660, 702 Superiority trial, 41 advanced, PC-RPLND, 709–710 Surgical lymph node staging, 837 clinical stage II A/B treatment, 690–692 Surrogate variable, 41 Sentinel node biopsy, 837–838 Surveillance, Epidemiology, and End Results (SEER) Serine peptidase inhibitor, Kazal type 1 (SPINK1), 170 program, 292 Sertoli cell tumors, 663 Survivin, 520 Severity of illness bias, 54 Sexual dysfunction, 271 Sexual function disturbances, 450 T Short bowel syndrome, 460 Tc99m diphosphonate, 22 Sickle cell disease, 486 Telomerase, 10 Single nucleotide polymorphism (SNP), 5 Temsirolimus, 606 Single photon emission computed tomography (SPECT Teratoma, 663 CT), 810–811 Testicular cancer, 684, 698 SIOP RTSG UMBRELLA protocol, 773, 778, 779 bone scan, 33 Sipuleucel-T, 249 clinical aspects, 31 Small renal masses clinical examination, 668 active surveillance (AS), 559–560 clinical presentation, 31–32 brachytherapy, 564–565 clinical stage II disease treatment, 689–695 clinical practice, 565 contralateral testis, biopsy of, 674 cryoablation, 562 CT scan, 33 diagnosis, 558–559 examination, 32 guideline-based ablation procedures, 560–561 follow-up for high-intensity focused ultrasound (HIFU), 562–563 anamnesis, 725 irreversible electroporation (IRE), 563 bone scan, 726 microwave ablation (MWA), 563–564 chest X-ray, 726 partial nephrectomy, 565 clinical examination, 725 868 Index

Testicular cancer (cont.) Toxicity, radiation, 217–219 CT scan, 726 TP53 gene, 12–13, 173, 746 duration and intervals, 727 Traditional transrectal ultrasound (TRUS), 142–144 duration to relapse, 728 Transforming growth factor-α (TGFα) group 1, 728–729 in kidney cancers, 8 group 2, 729, 730 in penile cancer, 11 group 3A, 729–730 Translocation carcinomas, 494 group 3B, 730–731 Transmembrane protease serine 2:ERG, 116–117 MRI, 726 Transperineal biopsy, prostate cancer, 144–145 recommendations, 725 Transrectal ultrasound, 21, 29 recurrence rate, 728 Transurethral resection of bladder tumors (TURBT), schedules, 724, 727–731 306, 330 target region, 728 anesthesia, 310 tumor markers, 726–727 antibiotic prophylaxis, 310 ultrasound, 725–726 biopsies during, 312–313 inguinal orchiectomy, 673–674 in bladder diverticulum, 312 inguinal surgical exploration, 669–670 in bladder dome, 312 magnetic resonance imaging, 668 complications, 313 molecular basics, 11–13 initial, 376 MRI, 33 narrow band imaging (NBI), 313–314 orchiectomy, 669–670 photodynamic diagnosis (PDD), 313–314 positron emission tomography, 34 preoperative diagnostics, 310 residual tumor management, 701–704 restaging, 379–380 serum tumor markers, 669 re-TURBT role, 314–315 staging diagnostics, 670 surgical technique, 310–312 symptoms, 668 treatment, 330 testicular prosthesis, 675 ureteral orifices involvement, 312 testis-sparing surgery, 674–675 Treatment effect, 41 tumor markers, 33 Treatment emergent, 41 ultrasonography, 32–33 Trichloroethylene exposure, 488–489 ultrasound, 668 Tuberous sclerosis complex (TSC), 492 See also Germ cell tumor of the testis (GCT) Tubulocystic renal cell carcinoma (tcRCC) Testicular dysgenesis syndrome (TDS), 658–659 definition, 547 Testicular germ cell tumor (TGCT), 11–13 histopathology, 547–548 Testicular intraepithelial neoplasia (TIN), see Germ cell immunohistochemistry, 547–548 neoplasia in situ (GCNIS) macroscopy, 547 Testicular prosthesis, 675 molecular pathology, 547–548 Testis-sparing surgery, 674–675 Tumor-infiltrating lymphocytes (TILs), 524 Testosterone-lowering therapy (Castration) Tumor necrosis, 521 bilateral orchiectomy, 258 Tumor suppressor genes, 4 medical androgen depletion, 258 Testosterone suppression, 256 The Cancer Genome Atlas (TCGA) U renal cell carcinomas, 492–493 UCLA-UISS risk model, 646 Third-generation TKIs, 607–608 Ultrasound Thrombocytosis, 522 advanced penile SCC, 797 Time lag bias, 55–56 prostate cancer, 29, 148 Tissue-based biomarkers renal cell carcinomas, 24, 502 carbonic anhydrase IX (CAIX), 519–520 testicular cancer, 32–33 C-met, 519 transducer types, 21 hypoxia-inducible factor (HIF-α) degradation, 519 types, 21 vascular endothelial growth factor (VEGF), 519 urothelial cancer, 26 Von Hippel-Lindau (VHL) gene, 517, 519 Ultrasound-guided fine needle aspiration cytology, 836–837 TMPRSS2-ERG fusion, 28, 169, 170 Upper urinary tract urothelial carcinoma (UTUC), 328 TNFRSF1A, 12 Ureteral orifices involvement, 312 TNM classification and staging, renal cell carcinomas, Urethral anastomosis complications, 463–464 507–508 Urethral carcinoma Tolerability, in clinical trials, 41 AJCC staging system, 739, 740 Tomotherapy, 213 bioptic assessment, 740 Index 869

clinical presentation, 739 microcystic, 417 follow-up, 742–743 micropapillary carcinomas, 415–416 histopathological grading, 739, 740 molecular basics, 6–7 histopathology of, 738 needle biopsy, 163 radiological imaging, 740 nested-type/large nested, 416–417 TNM staging system, 739 non-papillary, 6 treatment options, 740–741 papillary, 6 urine cytology, 739–740 plasmacytoid, 414–415 Urethral-sparing treatment, 742 sarcomatoid, 418–419 Urethra pressure profile, 441 Urothelial dysplasia, 338 Urethrectomy, 742 US-based Prostate, Lung, Colon, and Ovary (PLCO) Urinary continence trial, 184 functional outcomes, 280 US Preventive Services Task Force (USPSTF), 102 nerve-sparing techniques and, 198 Urinary cytology (UC) bladder cancer, 305 V non-muscle-invasive bladder cancer, 329 Vacuum erection device (VED), 452–455 Urinary diversion, 363–364 Vascular endothelial growth factor (VEGF), 8, 519, metabolic changes, 456 522, 541 Urinary incontinence Vemurafenib, 62 change in lifestyle, 448 Vena cava tumor thrombus instrumental urinary diversion and urostomy, 442–450 perioperative complications, 590 physiology under resting conditions, 440 prognostic factors, 589–590 physiology under stress, 441 surgical techniques, 588–589 qualified multimodal continence training, 442–448 survival, 590 (see also Multimodal continence training) Verrucous carcinoma, 789 stress incontinence, insufficient pelvic floor, 442 Vested interest bias, 54 supplies, postoperative phase, 441–442 Video endoscopic lymphadenectomy, 838 Urinary marker tests Vimentin, 521 bladder cancer, 305 Vitamin B12 deficiency, 458 non-muscle-invasive bladder cancer, 329–330 Vitamin D deficiency, 458 Urinary morbidity, chronic, 221 Von Hippel-Lindau (VHL) gene, 517, 519 Urinary toxicity Von Hippel-Lindau (VHL) syndrome acute, 221 molecular basics, 8 subacute, 221 renal cell carcinomas, 490–491 Urinary tract infection after cystectomy, 455–456 renal cell carcinomas, 486–487 W Urinary tract urothelial carcinoma (UTUC), 26 WAGR-syndrome, 775 Urine tests, bladder cancer, 305 Warty-basaloid carcinoma, 791 Urologic tumors, in childhood, 773–780 Warty carcinoma, 790–791 UroNav, 152 Warty PeIN, 786 Urostation®, 151–152 Watchful waiting, 560 Urostomy, instrumental urinary diversion and, White light cystoscopy (WLC), 306 442–450 WHO blue book, 479 Urothelial cancer WHO/International Society of Urological Pathology clinical aspects, 25 (ISUP) grading system, 539 clinical presentation, 25 Wilms tumor (WT) CT urography, 25–26 associated syndromes/risk factors, 775–776 imaging, 25 biology, 776 laboratory investigations, 25 classic triphasic, 776 MR urography, 27 computed tomography, 777, 778 ultrasonography, 26 diagnosis, 777–778 Urothelial carcinoma epidemiology, 774–775 bone metastases with, 87 histopathological classification, 776 classification, 414 laparoscopic-assisted approach, 780 clear cell, 417–418 magnetic resonance imaging, 777 giant cell, 417 nephron-sparing surgery, 779 lymphoepithelioma-like, 418–419 prognosis, 780 870 Index

Wilms tumor (WT) (cont.) X radiation therapy, 780 X-ray, 20 SIOP classification, 776 renal cell carcinomas, 506 survival rates, 774, 775 testicular cancer, 726 treatment, 778–780 ultrasound, 777 Withdrawal bias, 55 Y Wnt/βÀcatenin pathway, 746 Yolk sac tumor, 661, 663 World Health Organization, 478, 480, 659 World Medical Association (WMA), 60, 61 Wrong design bias, 54