BACKGROUND: We tested for upgrading (Gleason grade group [GGG] ≥ 4) and/or upstaging to non-organ-confined stage ([NOC] ≥ pT3/pN1) in intermediate unfavorable-risk (IU) prostate cancer (PCa) patients treated with radical prostatectomy, since both change the considerations for dose and/or type of radiotherapy (RT) and duration of androgen deprivation therapy (ADT). METHODS: We relied on Surveillance, Epidemiology, and End Results (2010-2015). Proportions of (a) upgrading, (b) upstaging, or (c) upgrading and/or upstaging were tabulated and tested in multivariable logistic regression models. RESULTS: We identified 7269 IU PCa patients. Upgrading was recorded in 479 (6.6%) and upstaging in 2398 (33.0%), for a total of 2616 (36.0%) upgraded and/or upstaged patients, who no longer fulfilled the IU grade and stage definition. Prostate-specific antigen, clinical stage, biopsy GGG, and percentage of positive cores, neither individually nor in multivariable logistic regression models, discriminated between upgraded and/or upstaged patients versus others. CONCLUSIONS: IU PCa patients showed very high (36%) upgrading and/or upstaging proportion. Interestingly, the overwhelming majority of those were upstaged to NOC. Conversely, very few were upgraded to GGG ≥ 4. In consequence, more than one-third of IU PCa patients treated with RT may be exposed to suboptimal dose and/or type of RT and to insufficient duration of ADT, since their true grade and stage corresponded to high-risk PCa definition, instead of IU PCa. Data about magnetic resonance imaging were not available but may potentially help with better stage discrimination.

Department of Maternal Child and Urological Sciences Policlinico Umberto 1 Hospital Sapienza University of Rome Rome Italy

Department of Surgical and Diagnostic Integrated Sciences University of Genova Genova Italy

Department of Urology 2nd Faculty of Medicine Charles University Praga Czech Republic

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Division of Experimental Oncology URI Urological Research Institute IRCCS San Raffaele Scientific Institute Milan Italy

Department of Urology Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia

Department of Urology Koc University Hospital Instanbul Turkey

Department of Urology Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany

Department of Urology University Hospital Frankfurt Frankfurt am Main Germany

Department of Urology University Hospital Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Dallas Texas USA

Department of Urology University of Verona Azienda Ospedaliera Universitaria Integrata di Verona Verona Italy

Departments of Urology Weill Cornell Medical College New York New York USA

Division of Urology Cancer Prognostics and Health Outcomes Unit University of Montréal Health Center Montréal Québec Canada

Division of Urology Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman Jordan

Zobrazit více v PubMed

Zumsteg ZS, Spratt DE, Pei I, et al. A new risk classification system for therapeutic decision making with intermediate‐risk prostate cancer patients undergoing dose‐escalated external‐beam radiation therapy. Eur Urol. 2013;64:895‐902. https://pubmed.ncbi.nlm.nih.gov/23541457/ PubMed

Wenzel M, Collà Ruvolo C, Nocera L, et al. Regional differences in patient age and prostate cancer characteristics and rates of treatment modalities in favorable and unfavorable intermediate risk prostate cancer across United States SEER registries. Cancer Epidemiol. 2021;74:101994. PubMed

Zumsteg ZS, Chen Z, Howard LE, et al. Number of unfavorable intermediate‐risk factors predicts pathologic upstaging and prostate cancer‐specific mortality following radical prostatectomy: results from the SEARCH database. Prostate. 2017;77:154‐163. https://pubmed.ncbi.nlm.nih.gov/27683213/ PubMed

Keane FK, Chen MH, Zhang D, et al. The likelihood of death from prostate cancer in men with favorable or unfavorable intermediate‐risk disease. Cancer. 2014;120:1787‐1793. https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.28609 PubMed DOI

Yang DD, Mahal BA, Muralidhar V, et al. Risk of upgrading and upstaging among 10 000 patients with Gleason 3+4 favorable intermediate‐risk prostate cancer. Eur Urol Focus. 2019;5:69‐76. https://pubmed.ncbi.nlm.nih.gov/28753811/ PubMed

Dinh KT, Muralidhar V, Mahal BA, et al. Occult high‐risk disease in clinically low‐risk prostate cancer with ≥50% positive biopsy cores: should national guidelines stop calling them low Risk? Urology. 2016;87:125‐132. https://pubmed.ncbi.nlm.nih.gov/26391387/ PubMed

Patel HD, Tosoian JJ, Carter HB, Epstein JI. Adverse pathologic findings for men electing immediate radical prostatectomy: defining a favorable intermediate‐risk group. JAMA Oncol. 2018;4:89‐92. https://pubmed.ncbi.nlm.nih.gov/28715578/ PubMed PMC

Morlacco A, Cheville JC, Rangel LJ, Gearman DJ, Karnes RJ. Adverse disease features in gleason score 3 + 4 “favorable intermediate‐risk” prostate cancer: implications for active surveillance. Eur Urol. 2017;72:442‐447. https://pubmed.ncbi.nlm.nih.gov/27574819/ PubMed

Martin NE, Chen MH, Zhang D, Richie JP, D'Amico AV. Unfavorable intermediate‐risk prostate cancer and the odds of upgrading to Gleason 8 or higher at prostatectomy. Clin Genitourin Cancer. 2017;15:237‐241. https://pubmed.ncbi.nlm.nih.gov/27426058/ PubMed

Zapatero A, Guerrero A, Maldonado X, et al. High‐dose radiotherapy with short‐term or long‐term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol. 2015;16:320‐327. http://www.thelancet.com/article/S1470204515700458/fulltext PubMed

Bolla M, Maingon P, Carrie C, et al. Short androgen suppression and radiation dose escalation for intermediate‐ and high‐risk localized prostate cancer: results of EORTC trial 22991. J Clin Oncol. 2016;34:1748‐1756. https://pubmed.ncbi.nlm.nih.gov/26976418/ PubMed

Mohler JL, Antonarakis ES, Armstrong AJ, et al. Prostate cancer, version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2019;17:479‐505. https://jnccn.org/view/journals/jnccn/17/5/article-p479.xml PubMed

Roach M, Moughan J, Lawton CAF, et al. Sequence of hormonal therapy and radiotherapy field size in unfavourable, localised prostate cancer (NRG/RTOG 9413): long‐term results of a randomised, phase 3 trial. Lancet Oncol. 2018;19:1504‐1515. https://pubmed.ncbi.nlm.nih.gov/30316827/ PubMed PMC

Pommier P, Chabaud S, Lagrange JL, et al. Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Update of the long‐term survival results of the GETUG‐01 randomized study. Int J Radiat Oncol Biol Phys. 2016;96:759‐769. https://pubmed.ncbi.nlm.nih.gov/27788949/ PubMed

Shakespeare TP, Wilcox SW, Aherne NJ. Can we avoid high levels of dose escalation for high‐risk prostate cancer in the setting of androgen deprivation? Onco Targets Ther. 2016;9:2819‐2824. https://pubmed.ncbi.nlm.nih.gov/27274277/ PubMed PMC

Partin AW, Kattan MW, Subong EN, et al. Combination of prostate‐specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer: a multi‐institutional update. JAMA. 1997;277:1445‐1451. https://jamanetwork.com/journals/jama/fullarticle/416070 PubMed

Ohori M, Kattan MW, Koh H, et al. Predicting the presence and side of extracapsular extension: a nomogram for staging prostate cancer. J Urol. 2004;171:1844‐1849. PubMed

Ward JF, Slezak JM, Blute ML, Bergstralh EJ, Zincke H. Radical prostatectomy for clinically advanced (cT3) prostate cancer since the advent of prostate‐specific antigen testing: 15‐year outcome. BJU Int. 2005;95:751‐756. https://pubmed.ncbi.nlm.nih.gov/15794776/ PubMed

Luzzago S, Palumbo C, Rosiello G, et al. The effect of radical cystectomy on survival in patients with metastatic urothelial carcinoma of the urinary bladder. J Surg Oncol. 2019;120:1266‐1275. https://pubmed.ncbi.nlm.nih.gov/31562831/ PubMed

Lantz A, Falagario UG, Ratnani P, et al. Expanding active surveillance inclusion criteria: a novel nomogram including preoperative clinical parameters and magnetic resonance imaging findings. Eur Urol Oncol. 2020; S2588‐9311(20): 30125‐5. https://pubmed.ncbi.nlm.nih.gov/32891599/ PubMed

Diamand R, Ploussard G, Roumiguié M, et al. External validation of a multiparametric magnetic resonance imaging‐based nomogram for the prediction of extracapsular extension and seminal vesicle invasion in prostate cancer patients undergoing radical prostatectomy. Eur Urol. 2021;79:180‐185. https://pubmed.ncbi.nlm.nih.gov/33023770/ PubMed

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. PubMed

Sorce G, Stabile A, Lucianò R, et al. Multiparametric magnetic resonance imaging of the prostate underestimates tumour volume of small visible lesions. BJU Int. 2021. (2):201‐207. “Mar, 09:59 AM” class=“new” updatedon=“29 Mar, 09:59 AM” mytype=“content” id=“ca89382c‐c342‐4748‐9807‐8c3ac0930ab2”>29(2):201‐207. https://pubmed.ncbi.nlm.nih.gov/34038039/ PubMed

Priester A, Natarajan S, Khoshnoodi P, et al. Magnetic resonance imaging underestimation of prostate cancer geometry: use of patient specific molds to correlate images with whole mount pathology. J Urol. 2017;197:320‐326. https://pubmed.ncbi.nlm.nih.gov/27484386/ PubMed PMC

Xue AL, Kalapara AA, Ballok ZE, et al. 68 Ga‐prostate‐specific membrane antigen positron emission tomography maximum standardized uptake value as a predictor of Gleason pattern 4 and pathological upgrading in intermediate‐risk prostate cancer. J Urol. 2021;207:341‐349. https://pubmed.ncbi.nlm.nih.gov/34546815/ PubMed

Koseoglu E, Kordan Y, Kilic M, et al. Diagnostic ability of Ga‐68 PSMA PET to detect dominant and non‐dominant tumors, upgrading and adverse pathology in patients with PIRADS 4‐5 index lesions undergoing radical prostatectomy. Prostate Cancer Prostatic Dis. 2021;24:202‐209. https://pubmed.ncbi.nlm.nih.gov/32826958/ PubMed

Mazzone E, Stabile A, Sorce G, et al. Age and gleason score upgrading between prostate biopsy and radical prostatectomy: is this still true in the multiparametric resonance imaging era? Urol Oncol. 2021;39:784.e1‐784.e9. https://pubmed.ncbi.nlm.nih.gov/33865687/ PubMed

Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI‐targeted or standard biopsy for prostate‐cancer diagnosis. N Engl J Med. 2018;378:1767‐1777. https://www.nejm.org/doi/full/10.1056/nejmoa1801993 PubMed DOI PMC

Panebianco V, Valerio MC, Giuliani A, et al. Clinical utility of multiparametric magnetic resonance imaging as the first‐line tool for men with high clinical suspicion of prostate cancer. Eur Urol Oncol. 2018;1:208‐214. https://moh-it.pure.elsevier.com/en/publications/clinical-utility-of-multiparametric-magnetic-resonance-imaging-as PubMed