Kontroverse ISUP-1-Prostatakarzinom: Ist der Karzinombegriff gerechtfertigt – klinische oder anatomische Definition?

Zusammenfassung

Hintergrund

Die Bezeichnung des Gleason-Score-6 (ISUP-Gradgruppe 1)-Prostatakarzinoms als „Krebs“ ist zunehmend Gegenstand kontroverser Diskussionen. Trotz exzellenter Prognose und geringer Metastasierungsrate führt die Diagnose häufig zu emotionaler Belastung und potenzieller Übertherapie. Die Frage nach einer alternativen, weniger stigmatisierenden Benennung gewinnt daher an Relevanz.

Ziel

Diese Übersichtsarbeit analysiert die Argumente für und gegen eine Umbenennung des ISUP-1-Prostatakarzinoms und beleuchtet, warum die Definition von Indolenz nicht allein durch histologische Kriterien bestimmt werden kann.

Methodik

Basierend auf aktueller Literatur und Konsensuspapieren internationaler Fachgesellschaften (ISUP/GUPS) werden pathologisch-anatomische, klinische, molekularbiologische und bildgebende Kriterien zur Definition von Tumorindolenz kritisch bewertet.

Ergebnisse

Weder morphologische Merkmale noch molekulare Marker oder Bildgebung allein ermöglichen eine verlässliche Identifikation indolenter Karzinome im Biopsat. Die diagnostische Unsicherheit wird durch die Interobservervariabilität zusätzlich verstärkt. Multidisziplinäre Strategien, die klinische, radiologische, molekulare und histopathologische Parameter integrieren, erscheinen erforderlich, um indolente Tumoren sicher zu erkennen und zu klassifizieren.

Schlussfolgerung

Eine bloße Umbenennung des GG1-Prostatakarzinoms in einen benigner klingenden Begriff greift zu kurz. Vielmehr ist eine individualisierte, multidimensionale Risikostratifizierung notwendig. Die Diskussion verdeutlicht, dass die Verantwortung für die Definition eines indolenten Karzinoms nicht allein bei der Pathologie liegen kann.

Abstract

Background

The designation of Gleason score 6 (ISUP Grade Group 1) prostate cancer as “cancer” has become increasingly controversial. Despite its excellent prognosis and minimal risk of metastasis, the diagnosis often leads to emotional distress and potential overtreatment. The question of whether a less alarming nomenclature might be more appropriate is gaining relevance.

Objective

This review analyses the arguments for and against renaming ISUP Grade Group 1 prostate cancer and explains why the definition of indolence cannot be based solely on histological criteria.

Methods

Drawing on current literature and consensus statements from international pathology societies (ISUP/GUPS), this article critically evaluates pathological, clinical, molecular, and imaging criteria used to define tumour indolence.

Results

Neither morphological characteristics, nor molecular markers, nor imaging alone can reliably identify indolent cancers in biopsy specimens. Diagnostic uncertainty is further amplified by significant interobserver variability. Multidisciplinary approaches that integrate clinical, radiological, molecular, and histopathological parameters appear necessary to accurately detect and classify indolent tumours.

Conclusion

Simply renaming GG1 prostate cancer using a less threatening term is insufficient. Instead, individualised, multidimensional risk stratification is essential. The debate underscores that the responsibility for defining indolent prostate cancer cannot rest solely with pathology.

Schlüsselwörter

Prostatakarzinom - Gleason-6 - ISUP 1 - Indolent

Keywords

prostate cancer - Gleason 6 - ISUP 1 - indolent

Publication History

Received: 10 June 2025

Accepted after revision: 15 October 2025

Article published online:
18 December 2025

• Literatur

• 1 Santucci C, Carioli G, Bertuccio P. et al. Progress in cancer mortality, incidence, and survival: a global overview. Eur J Cancer Prev 2020; 29: 367-381
• 2 Goerling U, Hinz A, Koch-Gromus U. et al. Prevalence and severity of anxiety in cancer patients: results from a multi-center cohort study in Germany. J Cancer Res Clin Oncol 2023; 149: 6371-6379
• 3 Labbate CV, Paner GP, Eggener SE. Should Grade Group 1 (GG1) be called cancer?. World J Urol 2022; 40: 15-19
• 4 Hamdy FC, Donovan JL, Lane JA. et al. Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med 2023; 388: 1547-1558
• 5 Eggener SE, Berlin A, Vickers AJ. et al. Low-Grade Prostate Cancer: Time to Stop Calling It Cancer. J Clin Oncol 2022; 40: 3110-3114
• 6 Epstein JI. Is Grade Group 1 (Gleason score 3+3=6) adenocarcinoma of the prostate really cancer?. Curr Opin Urol 2022; 32: 91-95
• 7 Epstein JI, Kibel AS. Renaming Gleason Score 6 Prostate to Noncancer: A Flawed Idea Scientifically and for Patient Care. J Clin Oncol 2022; 40: 3106-3109
• 8 Stroomberg HV, Larsen SB, Kjær Nielsen T. et al. Outcomes of Biopsy Grade Group 1 Prostate Cancer Diagnosis in the Danish Population. Eur Urol Oncol 2024; 7: 770-777
• 9 Totten RS, Heinemann MW, Hudson PB. et al. Microscopic differential diagnosis of latent carcinoma of prostate. AMA Arch Pathol 1953; 55: 131-141
• 10 Gleason DF. Classification of prostatic carcinomas. Cancer Chemother Rep 1966; 50: 125-128
• 11 Epstein JI, Allsbrook WC, Amin MB. et al. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 2005; 29: 1228-1242
• 12 Epstein JI, Egevad L, Amin MB. et al. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System. Am J Surg Pathol 2016; 40: 244-252
• 13 van Leenders GJLH, van der Kwast TH, Grignon DJ. et al. The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma. Am J Surg Pathol 2020; 44: e87-e99
• 14 Esserman LJ, Thompson IM, Reid B. et al. Addressing overdiagnosis and overtreatment in cancer: a prescription for change. Lancet Oncol 2014; 15: e234-e242
• 15 Berman DM, Epstein JI. When is prostate cancer really cancer?. Urol Clin North Am 2014; 41: 339-346
• 16 Eggener SE, Berlin A, Vickers AJ. et al. Low-Grade Prostate Cancer: Time to Stop Calling It Cancer. J Clin Oncol 2022; 40: 3110-3114
• 17 Campbell PA, Conrad RJ, Campbell CM. et al. Papillary urothelial neoplasm of low malignant potential: reliability of diagnosis and outcome. BJU Int 2004; 93: 1228-1231
• 18 Jones TD, Cheng L. Papillary urothelial neoplasm of low malignant potential: evolving terminology and concepts. J Urol 2006; 175: 1995-2003
• 19 Hentschel AE, van Rhijn BWG, Bründl J. et al. Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019?. Urol Oncol 2020; 38: 440-448
• 20 Nikiforov YE, Seethala RR, Tallini G. et al. Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncol 2016; 2: 1023-1029
• 21 Parente DN, Kluijfhout WP, Bongers PJ. et al. Clinical Safety of Renaming Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: Is NIFTP Truly Benign?. World J Surg 2018; 42: 321-326
• 22 Epstein JI, Kibel AS. Renaming Gleason Score 6 Prostate to Noncancer: A Flawed Idea Scientifically and for Patient Care. J Clin Oncol 2022; 40: 3106-3109
• 23 Shah RB, Paner GP, Cheng L. et al. Genitourinary Pathology Society and International Society of Urological Pathology White Paper on Defining Indolent Prostate Cancer: Call for a Multidisciplinary Approach. Eur Urol 2025; 88: 8-10
• 24 Stamey TA, Freiha FS, McNeal JE. et al. Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer 1993; 71: 933-938
• 25 Epstein JI, Walsh PC, Carmichael M. et al. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 1994; 271: 368-374
• 26 Ross HM, Kryvenko ON, Cowan JE. et al. Do adenocarcinomas of the prostate with Gleason score (GS) ≤6 have the potential to metastasize to lymph nodes?. Am J Surg Pathol 2012; 36: 1346-1352
• 27 Kweldam CF, Wildhagen MF, Bangma CH. et al. Disease-specific death and metastasis do not occur in patients with Gleason score ≤6 at radical prostatectomy. BJU Int 2015; 116: 230-235
• 28 Gleason DF. Undergrading of prostate cancer biopsies: a paradox inherent in all biologic bivariate distributions. Urology 1996; 47: 289-291
• 29 Launer BM, Ellis TA, Scarpato KR. A contemporary review: mpMRI in prostate cancer screening and diagnosis. Urol Oncol 2025; 43: 15-22
• 30 Ahdoot M, Wilbur AR, Reese SE. et al. MRI-Targeted, Systematic, and Combined Biopsy for Prostate Cancer Diagnosis. N Engl J Med 2020; 382: 917-928
• 31 Gandaglia G, Ploussard G, Valerio M. et al. The Key Combined Value of Multiparametric Magnetic Resonance Imaging, and Magnetic Resonance Imaging-targeted and Concomitant Systematic Biopsies for the Prediction of Adverse Pathological Features in Prostate Cancer Patients Undergoing Radical Prostatectomy. Eur Urol 2020; 77: 733-741
• 32 Inoue LYT, Trock BJ, Partin AW. et al. Modeling grade progression in an active surveillance study. Stat Med 2014; 33: 930-939
• 33 Allsbrook WC, Mangold KA, Johnson MH. et al. Interobserver reproducibility of Gleason grading of prostatic carcinoma: general pathologist. Hum Pathol 2001; 32: 81-88
• 34 Allsbrook WC, Mangold KA, Johnson MH. et al. Interobserver reproducibility of Gleason grading of prostatic carcinoma: urologic pathologists. Hum Pathol 2001; 32: 74-80
• 35 Kweldam CF, Nieboer D, Algaba F. et al. Gleason grade 4 prostate adenocarcinoma patterns: an interobserver agreement study among genitourinary pathologists. Histopathology 2016; 69: 441-449
• 36 Stroomberg HV, Larsen SB, Kjær Nielsen T. et al. Outcomes of Biopsy Grade Group 1 Prostate Cancer Diagnosis in the Danish Population. Eur Urol Oncol 2024; 7: 770-777
• 37 Haffner MC, Mosbruger T, Esopi DM. et al. Tracking the clonal origin of lethal prostate cancer. J Clin Invest 2013; 123: 4918-4922
• 38 Baca SC, Prandi D, Lawrence MS. et al. Punctuated evolution of prostate cancer genomes. Cell 2013; 153: 666-677
• 39 Mosquera J-M, Mehra R, Regan MM. et al. Prevalence of TMPRSS2-ERG fusion prostate cancer among men undergoing prostate biopsy in the United States. Clin Cancer Res 2009; 15: 4706-4711
• 40 Trock BJ, Fedor H, Gurel B. et al. PTEN loss and chromosome 8 alterations in Gleason grade 3 prostate cancer cores predicts the presence of un-sampled grade 4 tumor: implications for active surveillance. Mod Pathol 2016; 29: 764-771
• 41 Salami SS, Hovelson DH, Kaplan JB. et al. Transcriptomic heterogeneity in multifocal prostate cancer. JCI Insight 2018; 3: e123468
• 42 Klein EA, Santiago-Jiménez M, Yousefi K. et al. Molecular Analysis of Low Grade Prostate Cancer Using a Genomic Classifier of Metastatic Potential. J Urol 2017; 197: 122-128
• 43 Cheng L, Poulos CK, Pan C-X. et al. Preoperative prediction of small volume cancer (less than 0.5 ml) in radical prostatectomy specimens. J Urol 2005; 174: 898-902
• 44 Nguyen JK, Magi-Galluzzi C. Unfavorable Pathology, Tissue Biomarkers and Genomic Tests With Clinical Implications in Prostate Cancer Management. Adv Anat Pathol 2018; 25: 293-303
• 45 Nguyen JK, Harik LR, Klein EA. et al. Proposal for an optimised definition of adverse pathology (unfavourable histology) that predicts metastatic risk in prostatic adenocarcinoma independent of grade group and pathological stage. Histopathology 2024; 85: 598-613
• 46 Ayala G, Tuxhorn JA, Wheeler TM. et al. Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer. Clin Cancer Res 2003; 9: 4792-4801
• 47 Porten SP, Whitson JM, Cowan JE. et al. Changes in prostate cancer grade on serial biopsy in men undergoing active surveillance. J Clin Oncol 2011; 29: 2795-2800
• 48 Tosoian JJ, Mamawala M, Epstein JI. et al. Active Surveillance of Grade Group 1 Prostate Cancer: Long-term Outcomes from a Large Prospective Cohort. Eur Urol 2020; 77: 675-682
• 49 Brisbane WG, Priester AM, Ballon J. et al. Targeted Prostate Biopsy: Umbra, Penumbra, and Value of Perilesional Sampling. Eur Urol 2022; 82: 303-310
• 50 Eggener SE, Rumble RB, Armstrong AJ. et al. Molecular Biomarkers in Localized Prostate Cancer: ASCO Guideline. J Clin Oncol 2020; 38: 1474-1494
• 51 Cornford P, van den Bergh RCN, Briers E. et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2024; 86: 148-163