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2016 Max Peters

Salvage for radiorecurrent prostate cancer


Patients undergoing primary radiotherapy for prostate cancer are at risk of recurrent disease. Recurrences are often confined to the prostate and therefore eligible for a second curative ablation, known as salvage. Salvage modalities are usually directed at the entire prostate volume, due to former difficulties in assessing localised recurrences. Because of previous radiation damage to the prostate and surrounding organs at risk (OAR), whole-gland salvage modalities are associated with significant toxicity rates.
As a result of recent developments in assessing prostate cancer location using multi-parametric MRI and different biopsy techniques, the attention has shifted to a focal treatment approach in the salvage setting. This is known as focal salvage. With this approach only the recurrent tumour area is targeted, which seems to maintain cancer control, but decreases toxicity rates.
Focal salvage Iodine-125 brachytherapy appears to be able to provide durable disease control, while minimising late severe genitourinary (GU) and gastrointestinal (GI) toxicity. However, for salvage brachytherapy in general, dose constraints are necessary for OAR to prevent late severe complications. In the primary setting, these are available for both late GU and GI toxicity. These restrictions are probably inaccurate for the salvage setting, since the repair capacity of OAR is compromised by previous radiation damage. The dose restrictions for the rectum, urethra and bladder as found in this thesis are lower than those used for primary brachytherapy.
Before implementation of these restrictions is possible, patients should be adequately selected for salvage. Failure rates for whole-gland salvage are often significant, indicating a role for prediction models assessing which patients are most eligible for treatment. Whole-gland salvage brachytherapy patients can be adequately selected using the disease free survival interval (DFSI) after primary therapy and their PSA-doubling time (PSADT) before salvage.
For focal salvage, there are no multivariable models available because series are usually limited. The model in this thesis for focal salvage high intensity focused ultrasound (HIFU) shows that the DFSI after primary radiotherapy, the pre-treatment PSA, PSADT, prostate volume and T-stage as assessed on MRI can adequately predict biochemical disease free survival up to 3 years follow-up.
Lastly, it seems focal salvage brachytherapy is the most cost-effective option, predominantly driven by the lower treatment costs and reduced toxicity rates for which follow-up treatment is indicated.


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