Even though the treatment results of radiotherapy for local prostate cancer are good in general terms (only some 5 % progress to the metastatic stage within five years), the scientific community still wants to improve the prognosis especially as regards patients with the most high-risk disease. Docetaxel chemotherapy given adjuvantly with external radiotherapy and androgen-deprivation therapy is one method that has been researched. However, docetaxel therapy includes the risk of serious side-effects that could be detrimental to the quality of life of the patient, including neuropathic pain, blood cell effects and potentially life-threatening infections.
In the American NRG Oncology RTOG 0521 trial, adjuvant docetaxel improved the survival of patients with a very high-risk disease. However, in other trials, the results have been negative, including the Scandinavian SPCG-13 trial which included patients with a high- or intermediate-risk disease.
“My research showed that in the SPCG-13 participants, patients who received adjuvant docetaxel had a worse total quality of life at six months compared to those who did not, and the same applied to functional ability and physical well-being. However, there were no significant differences in a long-term follow-up of 1−4 years,” Miikka Lehtonen says.
Even though many new therapies have emerged in the past decade, docetaxel is the most common therapy in the treatment of late-stage castration-resistant and metastatic prostate cancer. The randomised and international PROSTY trial examined the biweekly docetaxel regimen in the standard triweekly dosing with an equal cumulative dose between the groups.
“Previous results have shown that the biweekly dosing decreases the risk of serious side-effects and even improves survival. In my research, I demonstrated that both treatments are equal for total quality of life, but a biweekly regimen can have small benefits as comes to, eg, emotional well-being,” Lehtonen mentions.
Local prostate cancer patients in a better shape than general male population
Lehtonen also compared the quality of life of patients, who received external radiotherapy for local prostate cancer without a hormonal treatment, to the general male population. In many respects, patients with local prostate cancer were in a better shape than their healthy peers. However, the patients experienced psychiatric symptoms – such as depression and distress – and bowel discomfort more frequently during the treatment, which had a negative impact on their quality of life. Moreover, at three months or later, the symptoms no longer occurred, but, as sexual side-effects are a known and adverse effect of radiotherapy, the sexual quality of the patients’ life was worse than that of their peers also in a long-term follow-up.
“New techniques – such as stereotactic body radiotherapy and intensity-modulated hypofractionated radiotherapy – have transformed the radiotherapy of prostate cancer, meaning fewer health visits and decreased costs. Our study included patients who were treated with these novel techniques. However, the long-term effects of stereotactic body radiation have not been researched from the perspective of quality of life, and thus far, international guidelines have not recommended it as a preferred treatment modality,” Lehtonen explains.
Lehtonen also researched the impact of comorbidity and performance status on the treatment results of external radiotherapy for local prostate cancer.
“Our novel finding was that comorbidity was a risk factor for worse overall survival even when performance status was included in the models as a confounding factor. This finding could benefit future research when we try to find the patients who do not benefit from aggressive treatment,” Lehtonen says.
Public defence on Friday 29 September
The doctoral dissertation of Licentiate of Medicine Miikka Lehtonen in the field of oncology and radiotherapy titled Quality of Life in Prostate Cancer Patients after External Beam Radiotherapy, Docetaxel Chemotherapy and Combined Therapy: And the Impact of Comorbidity and Performance Status on the Survival after External Beam Radiotherapy will be publicly examined at the Faculty of Medicine and Health Technology of Tampere University at 12.00 on Friday 29 September 2023. The venue is auditorium F114 of Arvo building on the Kauppi campus, address Arvo Ylpön katu 34. The Opponent will be docent Hanna Mäenpää from Tampere University while professor emerita Pirkko-Liisa Kellokumpu-Lehtinen from Tampere University will act as the custos.
The doctoral dissertation is available online.
The public defence can be followed via a remote connection.
Photo: Henri Peltola