EAU 2021: Rapid-Fire Debate: Otherwise Healthy Patient with T1HG Disease plus CIS; What Is the Best Treatment?

(UroToday.com) The 2021 European Association of Urology (EAU) annual meeting had a Controversies in Bladder Cancer 2021: Rapid-fire debates session. The session was introduced by Dr. Ashish Kamat with chairs of the session, Professors Joan Palou and Arnulf Stenzl. There were five rapid-fire debates with case-based discussions, multiple presenters have the opportunity to discuss nuances of common dilemmas facing urologic oncology patients and providers and to use these evidence-based debates to provide clear, rational guidance on the timely management of difficult situations in bladder cancer.

In this rapid fire debate, the focus is on the management of HG T1 bladder cancer with concurrent CIS. Dr. Palou argues for intravesical therapy while Dr. Witjes argues for upfront radical cystectomy.


Case: This is a forty five year old woman, corportate executive, married, 2 children, very fit. Prior history of TB as a child. Active smoker (20 cigs/day, 25 years). She had recurrent urinary tract infections. Referred to her urologist after one year hematuria.

  • Cysto: 3cm+ lesion plus 2 small satellite lesions
  • Cytology negative
  • Imaging: Upper urinary tract normal
  • TURBT – pT1 HG urothelial carcinoma with concurrent CIS. Muscle present in specimen. Micropapillary histology.

Dr. Palao ops for the conservative approach.

First he highlights the importance of quality initial TURBT. You need to see muscle in the specimen and at the time the resection. So if you’re worried about the quality of the initial TURBT, you must go back for re-resection and maximally resect visible tumor.

Under staging at TURBT is a real concern.

  • Re-TURBT can identify T2 disease in ~15-20% of specimens. But this can higher at centers with less experience.
  • Even at his own center, they found a 17% residual tumor.

Next he focused on the micropapillary histology. In a study by Willis et al.1 of patients with cT1 micropapillary UC, patients did better with early cystectomy. Patients with focal micropapillary had much better outcomes than those with extensive micropapillary component (73% 5-year DSS for focal vs, 42% 5-year DSS for extensive). A subsequent paper by Gaya et al.2 demonstrated that incremental increase in micropapillary variant is associated with worse survival – but those with <10% have excellent outcomes, similar to pure urothelial. Those with >50% however, do quite poorly.

With regards to the CIS presence, he notes that CIS in the prostatic urethra (in males) and any CIS in females is a poor prognostic factor and associated with shorter time to progression and worse disease specific survival.3 but, while the presence of CIS is important, should not change upfront management in this patient.

So, in this candidate with established cT1 disease, small percentage micropapillary disease, and CIS, they should stick with intravesical therapy.

Dr. Witjes argues for early cystectomy. He notes that the EAU guidelines recommend discussing early cystectomy with patients at the highest risk of tumor progression (which this patient is) and that the AUA guidelines recommend that in a fit patients with T1 tumors and CIS or variant histology, radical cystectomy should be offered.

His first comment is the risk of upstaging. 10-20% of  pT1 tumors on initial resection are upstaged (per EAU guidelines). He notes that there is increasing data on the use of MRI and VIRADS scoring to help locally stage tumors, and can help differentiate T1 and T2 tumors. But, in this patient, a repeat resection is warranted.

With regards to progression, T1 high grade patients do poorly – 1-5 years progression rates are 11.4-19.8%, which needs to be discussed with this young fit woman. The most important risk factors for progression are CIS, size > 3 cm, older age, LVI and pT1b/c disease – and this patient has multiple risk factors.

He alluded once more to something Dr. Kamat has often shared – disease specific survival in a patient with HG T1 bladder cancer is equal to a man with cT3b GG5 12/12 core positive prostate cancer with PSA 75. Would you plan conservative therapy in that patient?

He notes that over 25 years of practice, he has become much more conservative in his management of prostate cancer, but much more aggressive in his management of high-risk non-muscle invasive bladder cancer.

Presented by:
Ashish Kamat, MD, MBBS, MD Anderson Cancer Center, Houston, Texas
Joan Palou, MD, Fundacio Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain
J. Alfred Witjes, MD, Ph.D., Full professor at the Radboud Institute for Molecular Life Sciences, Faculty of Medical Sciences, Chair of Oncological Urology, Radboud University Medical Centre, Nijmegen, Netherlands


Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.

References:
  1. Willis DL, Fernandez MI, Dickstein RJ, Parikh S, Shah JB, Pisters LL, Guo CC, Henderson S, Czerniak BA, Grossman HB, Dinney CP, Kamat AM. Clinical outcomes of cT1 micropapillary bladder cancer. J Urol. 2015 Apr;193(4):1129-34. doi: 10.1016/j.juro.2014.09.092. Epub 2014 Sep 22. PMID: 25254936; PMCID: PMC4687395.
  2. Gaya JM, Palou J, Algaba F, Arce J, Rodríguez-Faba O, Villavicencio H. The case for conservative management in the treatment of patients with non-muscle-invasive micropapillary bladder carcinoma without carcinoma in situ. Can J Urol. 2010 Oct;17(5):5370-6. PMID: 20974029.
  3. Palou J, Sylvester RJ, Faba OR, Parada R, Peña JA, Algaba F, Villavicencio H. Female gender and carcinoma in situ in the prostatic urethra are prognostic factors for recurrence, progression, and disease-specific mortality in T1G3 bladder cancer patients treated with bacillus Calmette-Guérin. Eur Urol. 2012 Jul;62(1):118-25. doi: 10.1016/j.eururo.2011.10.029. Epub 2011 Oct 25. PMID: 22101115.
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