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Traveling the prostate cancer timeline in chase of treatment paradigms Can we cure the incurable?

Boek - Dissertatie

Summary In this thesis, we travelled the PCa timeline in search for treatment paradigms, and re-introduced radiotherapy in different disease settings. In Chapter 3 we investigated the benefit of adding elective para-aortic lymph node irradiation to the prostate (bed), pelvic lymph nodes irradiation and long-term hormonal treatment in the PART study, a multicentre single-arm phase 2 trial. We tried to answer to the question if adding elective para-aortic lymph node radiotherapy can improve clinical progression-free survival and if this treatment is feasible in terms of toxicity. At time of the dissertation the PART trial was still ongoing, with 93 patients included in the trial. Our preliminary results demonstrate that extended RT fields used in the treatment of pN1 prostate cancer do not result in an excess of GU or GI toxicity. Hematological toxicity was acceptable, however substantial acute and late grade 3 lymphopenia was seen. At time of last follow-up, recuperation to baseline ALC was seen in only 10% of the patients. Whether this treatment approach will result in better CSS survival is to be awaited. In Chapter 4 we focussed on the patients with pN0 disease, who experienced biochemical recurrence (BCR) after treatment of the primary tumor with radical prostatectomy (RP) and lymph node dissection. Salvage radiotherapy (SRT) is the only curative treatment at that moment. Many questions remain about the optimal duration of hormonal treatment. We therefore developed a randomized controlled trial to evaluate the effect on distant metastasis-free survival (DMFS) of short (6 months) versus long-term (24 months) duration of androgen deprivation therapy (ADT) as adjuvant treatment to high dose SRT, for patients who experience BCR after radiotherapy (RT) and who have a pN0 status. In Chapter 5 we focussed on the optimal treatment for oligorecurrent prostate cancer, as it has been shown in prospective randomized controlled trials that the use of metastasis-directed therapy (MDT) can postpone the start of palliative ADT. However, because of the long natural history of PCa, it remains difficult to determine the effect on novel treatment options. In this chapter we reported on long-term palliative ADT and metastatic castration-refractory prostate cancer (mCRPC)-free survival of oligorecurrent post-RP patients treated by MDT at the University Hospitals of Leuven. Estimated median palliative-ADT free survival was 66 months (95% CI 58-164) and estimated median mCRPC-free survival was not reached (mean 117 months, 95% CI 103-132). In total, 314 MDTs were performed and 25 patients (13%) received ≥3 MDTs. This study demonstrated that (repeated) MDT is feasible and holds promise in terms of palliative ADT-free and mCRPC-free survival for patients with oligorecurrent PCa. In the last chapter, Chapter 6, we investigated on the use of MDT for oligoprogressive mCRPC, in order to evaluate of we can perform MDT for patients presenting with oligoprogressive disease, while continuing otherwise successful ongoing systemic treatment. Will this lead to a substantial postponement of next-line systemic treatment (NEST)? Firstly, we performed a retrospective analysis on patients in the mCRPC setting treated with MDT for oligoprogression at the University Hospitals of Leuven and the University Hospitals of Ghent. With a median NEST-free survival of 16 months (95% confidence interval [CI] 10-22) and progression-free survival of 10 months (95% CI 6-15) with only minor radiotherapy- or surgery-related toxicity, results were very promising. This led to the initiation of the MEDCARE trial phase 2, with the aim to prospectively confirm the retrospective findings and serve as a base for a randomised phase 3 trial. Preliminary results of the MEDCARE trial confirm the promising results of treatment of oligoprogressive lesions with MDT with negligible toxicity. Imaging with PSMA PET-CT provides some additional information, with change of management in the majority (83%) of the cases.
Jaar van publicatie:2021
Toegankelijkheid:Closed