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Advanced Bladder Cancer. Aspects of Diagnosis and Treatment.

Abrahamsson, Johan LU (2021) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Treatment of bladder cancer has seen few advancements in recent decades until the introduction of checkpoint inhibitors during the last few years. Bladder cancer diagnostics have been similarly impaired and the likely advent of novel treatments in the neoadjuvant setting will require new diagnostic tools in the preoperative setting in muscleinvasive bladder cancer.
This thesis evaluates three diagnostic tools with a particular focus on guiding treament before or during neoadjuvant or induction chemotherapy. Firstly, we show that presence of a single CTC with CellSearch is associated with earlier progression in patients with advanced bladder cancer as well as metastatic disease on FDG-PET-CT. A significant proportion of bladder cancer... (More)
Treatment of bladder cancer has seen few advancements in recent decades until the introduction of checkpoint inhibitors during the last few years. Bladder cancer diagnostics have been similarly impaired and the likely advent of novel treatments in the neoadjuvant setting will require new diagnostic tools in the preoperative setting in muscleinvasive bladder cancer.
This thesis evaluates three diagnostic tools with a particular focus on guiding treament before or during neoadjuvant or induction chemotherapy. Firstly, we show that presence of a single CTC with CellSearch is associated with earlier progression in patients with advanced bladder cancer as well as metastatic disease on FDG-PET-CT. A significant proportion of bladder cancer cells express EpCAM and can be detected using EpCAM-antigen based methods.
Secondly, in the setting of induction chemotherapy, complete metabolic response with FDG-PET-CT is associated with survival compared to a partial response during chemotherapy followed by radical cystectomy in patients with nodepositive
bladder cancer. In a similar vein, we find that the CellSearch method is not feasible in monitoring chemosensitivity due to the low sensitivity of the method. Finally, bladder cancers of the luminal-like (GU- and Uro) subtypes display improved outcomes following cisplatin-based neoadjuvant chemotherapy compared to the Ba/Sq
subtype. The methods presented in this thesis are not mutually exclusive but rather constitute reciprocal biomarkers providing information about risk of occult metastatic disease, predicted and actual response to chemotherapy at time-points where
such information can be clinically useful. Novel neoadjuvant treatment options for bladder cancer will likely result in a renaissance in preoperative diagnostics as alternative treatments will allow for randomized study designs for biomarkers. Future diagnostic workups will likely entail an extended suite of such biomarkers and diagnostic tools to provide all aspects of a patient’s disease. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • professor Thalmann, George, Department of Urology, University of Bern, Inselspital ,Bern, Switzerland
organization
publishing date
type
Thesis
publication status
published
subject
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2021:137
pages
59 pages
publisher
Lund University, Faculty of Medicine
defense location
Agardh föreläsningssal, CRC, Jan Waldenströms gata 35, Skånes Universitetssjukhus i Malmö. Join by Zoom: https://lu-se.zoom.us/j/66845426043
defense date
2021-12-01 13:00:00
ISSN
1652-8220
ISBN
978-91-8021-144-4
language
English
LU publication?
yes
id
e32c8a61-43c5-4c9b-86f1-3082117679b3
date added to LUP
2021-11-22 16:10:17
date last changed
2023-02-06 11:22:53
@phdthesis{e32c8a61-43c5-4c9b-86f1-3082117679b3,
  abstract     = {{Treatment of bladder cancer has seen few advancements in recent decades until the introduction of checkpoint inhibitors during the last few years. Bladder cancer diagnostics have been similarly impaired and the likely advent of novel treatments in the neoadjuvant setting will require new diagnostic tools in the preoperative setting in muscleinvasive bladder cancer.<br/>This thesis evaluates three diagnostic tools with a particular focus on guiding treament before or during neoadjuvant or induction chemotherapy. Firstly, we show that presence of a single CTC with CellSearch is associated with earlier progression in patients with advanced bladder cancer as well as metastatic disease on FDG-PET-CT. A significant proportion of bladder cancer cells express EpCAM and can be detected using EpCAM-antigen based methods.<br/>Secondly, in the setting of induction chemotherapy, complete metabolic response with FDG-PET-CT is associated with survival compared to a partial response during chemotherapy followed by radical cystectomy in patients with nodepositive<br/>bladder cancer. In a similar vein, we find that the CellSearch method is not feasible in monitoring chemosensitivity due to the low sensitivity of the method. Finally, bladder cancers of the luminal-like (GU- and Uro) subtypes display improved outcomes following cisplatin-based neoadjuvant chemotherapy compared to the Ba/Sq<br/>subtype. The methods presented in this thesis are not mutually exclusive but rather constitute reciprocal biomarkers providing information about risk of occult metastatic disease, predicted and actual response to chemotherapy at time-points where<br/>such information can be clinically useful. Novel neoadjuvant treatment options for bladder cancer will likely result in a renaissance in preoperative diagnostics as alternative treatments will allow for randomized study designs for biomarkers. Future diagnostic workups will likely entail an extended suite of such biomarkers and diagnostic tools to provide all aspects of a patient’s disease.}},
  author       = {{Abrahamsson, Johan}},
  isbn         = {{978-91-8021-144-4}},
  issn         = {{1652-8220}},
  language     = {{eng}},
  number       = {{2021:137}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Advanced Bladder Cancer. Aspects of Diagnosis and Treatment.}},
  url          = {{https://lup.lub.lu.se/search/files/110008923/Advanced_Bladder_Cancer.pdf}},
  year         = {{2021}},
}