Contemporary Staging for Muscle-Invasive Bladder Cancer: Accuracy and Limitations - Beyond the Abstract

Nearly half of patients undergoing radical cystectomy (RC) are clinically under-staged.1,2 The causes for this are many, but likely contributors include shortcomings in our ability to identify extravesical disease components in the primary tumor with histologic assessment (pT2 vs. pT3a) or bimanual examination (pT2 vs. ≥pT3b) as well as to identify occult nodal metastasis in regional lymph nodes which do not meet radiographic size criteria. The Vesical Imaging Reporting and Data System (VI-RADS) multiparametric MRI scoring system shows promising performance in objectively staging primary bladder tumors with reliable inter-observer agreement in predicting MIBC.3,4 MRI appears to have a similar diagnostic accuracy compared to CT for clinically staging normal-sized or minimally enlarged lymph nodes.


The reference standard treatment for MIBC is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy. Clinical substaging of primary tumors (ie. T2a/b, T3a/b) is arguably a moot point if patients are to be managed with this one-size-fits-all approach. However, attempts at risk-stratified approaches to neoadjuvant therapy5,6 or bladder preservation after clinical response to systemic therapy (as evaluated in the ongoing RETAIN [NCT 02710734], HCRN GU 16-257 [03558087], Alliance A031701 [03609216] trials) place due to emphasis on accurate clinical staging of the primary tumor.

Our patients would also benefit from improved clinical staging after local or systemic therapy to identify the subset of patients who are successfully managed without extirpative radical surgery. These would include patients who are rendered disease free with a complete endoscopic resection alone. These patients, along with those achieving a meaningful clinical response to systemic therapy, would be best managed with bladder preservation. However, imaging modalities which can reliably detect occult extravesical disease components (≥cT3 or cN+) are crucial for this success of this approach in the real-world setting. In the future, it is also possible that biomarkers informative of tumor burden (ie. circulating tumor DNA) and/or predictive of therapeutic response (ie. DNA damage response gene alterations) will better triage patients for these bladder preserving strategies.

Written by: Patrick J. Hensley, MD, & Ashish M. Kamat, MD, MBBS, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

References:

  1. Hollenbeck BK, Miller DC, Dunn RL, Montie JE, Wei JT. The effects of stage divergence on survival after radical cystectomy for urothelial cancer. Urol Oncol. 2005;23(2):77-81.
  2. Fritsche HM, Burger M, Svatek RS, et al. Characteristics and outcomes of patients with clinical T1 grade 3 urothelial carcinoma treated with radical cystectomy: results from an international cohort. Eur Urol. 2010;57(2):300-309.
  3. Barchetti G, Simone G, Ceravolo I, et al. Multiparametric MRI of the bladder: inter-observer agreement and accuracy with the Vesical Imaging-Reporting and Data System (VI-RADS) at a single reference center. Eur Radiol. 2019;29(10):5498-5506.
  4. Del Giudice F, Barchetti G, De Berardinis E, et al. Prospective Assessment of Vesical Imaging Reporting and Data System (VI-RADS) and Its Clinical Impact on the Management of High-risk Non-muscle-invasive Bladder Cancer Patients Candidate for Repeated Transurethral Resection. Eur Urol. 2020;77(1):101-109.
  5. Culp SH, Dickstein RJ, Grossman HB, et al. Refining patient selection for neoadjuvant chemotherapy before radical cystectomy. J Urol. 2014;191(1):40-47.
  6. Hensley PJ, Bree KK, Campbell MT, et al. Progression of Disease after BCG Therapy: Refining Patient Selection for Neoadjuvant Chemotherapy before Radical Cystectomy. J Urol. 2021:101097ju0000000000001943.

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