© 2009 THE AUTHORS 206 JOURNAL COMPILATION © 2 0 0 9 B J U I N T E R N A T I O N A L | 1 0 6 , 2 0 6 – 2 11 | doi:10.1111/j.1464-410X.2009.09100.x 2009 THE AUTHORS. JOURNAL COMPILATION 2009 BJU INTERNATIONAL Urological Oncology PATHOLOGY REVIEW IN pT1 BLADDER CANCER VAN RHIJN ET AL. Pathological stage review is indicated in primary pT1 bladder cancer Bas W.G. van Rhijn* † , Theo H. van der Kwast ‡§ , David M. Kakiashvili*, Neil E. Fleshner*, Madelon N.M. van der Aa † , Sultan Alkhateeb*, Chris H. Bangma † , Michael A.S. Jewett* and Alexandre R. Zlotta ¶ *Department of Surgical Oncology, Division of Urology, ‡ Department of Surgical Pathology, University Health Network, ¶ Department of Urology, Mount Sinai Hospital, Toronto, Canada, and Departments of † Urology and § Pathology, Erasmus MC, Rotterdam, the Netherlands Accepted for publication 9 September 2009 multivariate analyses compared the predictive value of age, gender, hospital, carcinoma in situ (CIS), tumour-size, reviewed grade and reviewed stage. RESULTS With a mean follow-up of 6.4 years, there was disease progression in 48 (29%) patients and 26 (16%) died from BC. Associated CIS was found in 55 (34%) patients. After reviewing the slides, 24 (15%) tumours were downstaged to pTa, 134 (82%) remained pT1 and six (4%) were upstaged to ≥pT2. The grade review resulted in 74 G2, 90 G3, 37 low-grade and 127 high-grade lesions for the two systems used. In multivariate analyses, reviewed stage (both P < 0.001) and CIS (P = 0.017 and 0.023) had independent significance for progression and disease-specific survival, respectively. CONCLUSION A stage review is indicated in pT1 BC, as almost 20% of pT1 tumours were up- or downstaged, and the reviewed stage predicted the patient’s prognosis. Hence, pathology review identified patients with different prognoses who might benefit from other treatment strategies than BCG. We confirmed that CIS is an unfavourable sign in pT1 bladder cancer. KEYWORDS bladder cancer, grade, stage, pathology review, pT1 Study Type – Diagnosis (case series) Level of Evidence 4 OBJECTIVE To evaluate the effect of a pathology review on the clinical outcome of patients with primary pT1 bladder cancer (BC), as the clinical course of such patients is variable. PATIENTS AND METHODS The slides of 164 primary (first diagnosis) pT1 bladder tumours from two university hospitals were reviewed by one pathologist for stage and grade (World Health Organization 1973 and 2004). Patients were initially managed conservatively with bacille Calmette-Guérin (BCG). Uni- and INTRODUCTION Up to 80% of bladder cancers (BC) are not muscle-invasive (NMI) at first diagnosis. In NMI BC, ≈70% initially present with pTa, 20% as pT1 (invasion of the subepithelial connective tissue, i.e. lamina propria) and 10% as carcinoma in situ (CIS) lesions [1,2]. These tumours represent a heterogeneous group with variable oncological outcomes [3–5]. Recurrence is the main problem for patients with pTa NMI BC, whereas progression to MI is the main threat in pT1 and CIS [3]. Adjuvant intravesical treatment with BCG has a protective effect against progression and is considered the treatment of first choice in most patients with high- risk NMI BC [6–8]. In pT1 BC the 5-year progression rates are reported as 20–40% [9,10], but driven by the high progression rates in pT1, the questionable long-term efficacy of BCG [6,7] and a lower response to BCG for pT1 than for pTa and CIS [11], there is controversy on the timing of radical cystectomy in patients with pT1 BC [10] and the search for prognostics variables continues. Several studies have shown that histological grade has significant prognostic information, especially for predicting progression [3,4]. The high interobserver variation (up to 50%) renders its use less suitable for predicting the prognosis in individual cases [5,12–14]. The WHO adopted a new classification system for grade in 2004 (papillary urothelial neoplasm of low malignant potential, LMP; low-grade, LG, and high-grade, HG, urothelial cancer) to improve the accuracy of grading [15]. Until the new system has been fully validated against the WHO 1973 system [16] that consists of three grades (G1–3), the European Association of Urology guideline recommends the use of both systems [8]. As outlined by Lopez-Beltran and Cheng [17], recognition of early invasion (stage pT1) in urothelial neoplasia is one of the most challenging areas in bladder pathology, and reproducibility between pathologists is a major issue. This, together with the proposal by some urologists to treat early invasive tumours more aggressively, makes the accurate detection of pT1 lesions even more relevant in clinical practice [17]. In recent years, the morphological features and patterns of invasion of tumour into the lamina propria have been more accurately characterized and standardized, and although some of the features are subtle, they can be of BJUI BJU INTERNATIONAL