Management of Locally Advanced Unresectable or Metastatic Urothelial Carcinoma: Expert Opinion from an Indian Panel via Delphi Consensus Method

Senthil Rajappa; T. Raja; Chirag Desai; Amit Joshi; Palanki Satya Dattatreya; Mohit Agarwal; Rahul Sud; Anita Ramesh; A. K. Vaid; Vineet Talwar; Amit Rauthan; Ashish Kaushal; Prabrajya Mohapatra; Akhil Kapoor

doi:10.1055/s-0042-1760317

Indian Journal of Medical and Paediatric Oncology, Table of Contents

CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(05): 365-375
DOI: 10.1055/s-0042-1760317

Review Article

Management of Locally Advanced Unresectable or Metastatic Urothelial Carcinoma: Expert Opinion from an Indian Panel via Delphi Consensus Method

Senthil Rajappa

¹Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India

,

T. Raja

²Department of Medical Oncology, Apollo Specialty Hospital, Chennai, Tamil Nadu, India

,

Chirag Desai

³Hemato-Oncology Clinic, Vedanta Institute of Medical Sciences, Ahmedabad, Gujarat, India

,

Amit Joshi

⁴Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India

,

Palanki Satya Dattatreya

⁵Department of Medical Oncology, Renova Soumya Hospital, Hyderabad, Telangana, India

,

Mohit Agarwal

⁶Department of Medical Oncology, Fortis Hospital, New Delhi, India

,

Rahul Sud

⁷Department of Medical Oncology, Command Hospital Airforce, Bangalore, Karnataka, India

,

Anita Ramesh

⁸Department of Medical Oncology, Saveetha Medical College and Hospital, Chennai, Tamil Nadu, India

,

A. K. Vaid

⁹Department of Medical Oncology and Haematology, Medanta Cancer Institute, Medanta – The Medicity, Gurgaon, Haryana, India

,

Vineet Talwar

¹⁰Department of Medical Oncology, Rajiv Gandhi Cancer Institute, Delhi, India

,

Amit Rauthan

¹¹Department of Medical Oncology, Hemato-Oncology and Transplant, Manipal Hospital, Bangalore, Karnataka, India

,

Ashish Kaushal

¹²Aagam Clinic, KD Hospital, Ahmedabad, Gujarat, India

,

Prabrajya Mohapatra

¹³Department of Medical Oncology, Apollo Gleneagles Hospital, Kolkata, West Bengal, India

,

Akhil Kapoor

¹⁴Department of Medical Oncology, Tata Memorial Hospital (TMH) (Homi Bhabha Cancer Hospital [HBCH] and Mahamana Pandit Madan Mohan Malaviya Cancer Centre [MPMMCC]), Varanasi, Uttar Pradesh, India

› Author Affiliations

Abstract

Introduction Currently, there are no guidelines for the management of locally advanced unresectable or metastatic urothelial carcinoma (mUC) from an Indian perspective. There is a lack of consensus on the utility of treatment options in first-line (1L) and second-line (2L) settings, especially in cisplatin- and platinum-unfit mUC patient subgroups.

Objective This articles aims to develop evidence-based practical consensus recommendations for the management of mUC in Indian settings.

Methods Modified Delphi consensus methodology was considered to arrive at a consensus. An expert scientific committee of 15 medical oncologists from India constituted the panel. Twelve clinically relevant questions were grouped into five categories for presentation and discussion: (1) cisplatin and platinum ineligibility criteria; (2) programmed death ligand 1 and fibroblast growth factor receptor (FGFR) testing in mUC patients; (3) treatment options in 1L settings; (4) role of switch maintenance; and (5) treatment options in 2L. Statements that reached high (≥ 80%) and moderate (60–79%) levels of consensus in the first round (electronic survey) did not undergo the second Delphi round. The questions that received a low level of consensus (< 60%) were discussed during the virtual meeting.

Results Renal impairment (creatinine clearance [CrCl] < 60 mL/min) and New York Heart Association class 3 heart failure are important assessment criteria for determining cisplatin ineligibility. Patients are unfit for any platinum-based chemotherapy in case of Eastern Cooperative Oncology Group performance status> 3 or severe renal impairment (CrCl < 30 mL/min). Gemcitabine and platinum with cisplatin over carboplatin were preferred in 1L settings. In patients unfit for cisplatin-based regimens, carboplatin–gemcitabine chemotherapy was preferred over immunotherapy (atezolizumab or pembrolizumab). Selected patients who are platinum ineligible may be considered for immunotherapy. Post-induction chemotherapy, those who do not progress may be strongly considered for avelumab maintenance. Experts recommended erdafitinib in FGFR-positive mUC patients in 2L settings. In FGFR-negative patients, immunotherapy (pembrolizumab, nivolumab, or avelumab) may be preferred over chemotherapy (paclitaxel, docetaxel, or vinflunine). Enfortumab vedotin and sacituzumab govitecan may be considered for further lines of therapy.

Conclusion Expert panel consensus will offer expert guidance to oncologists/clinicians on the management of mUC in Indian settings.

Key Points

In 1L settings, the experts preferred gemcitabine and platinum with cisplatin over carboplatin in mUC patients.
In patients unfit for cisplatin-based regimens, carboplatin–gemcitabine chemotherapy was preferred over immunotherapy (atezolizumab or pembrolizumab). Selected patients who are platinum ineligible (cisplatin and carboplatin) may be considered for immunotherapy (atezolizumab or pembrolizumab) in 1L. Post-induction chemotherapy, those who do not progress should be strongly considered for avelumab switch maintenance.
Erdafitinib was recommended in FGFR-positive mUC patients in 2L.
In FGFR-negative patients, platinum-based chemotherapy was suggested in 2L for those relapsing late, immunotherapy (pembrolizumab, nivolumab, or avelumab) for those who did not receive targeted immunotherapy in 1L, and single-agent chemotherapy (paclitaxel, docetaxel, or vinflunine) for other mUC patients.

Keywords

bladder cancer - metastatic urothelial carcinoma - locally advanced - India - management - consensus - Delphi

Full Text

References

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Supplementary Material