The role of radiation therapy in metastatic kidney cancer remains controversial. Recently, a prospective study evaluated the feasibility of definitive radiotherapy instead of systemic therapy for oligometastatic kidney cancer, and whether progression-free survival (PFS) can be prolonged and systemic therapy delayed. Recently, the findings were published in the prestigious international journal Lancet Oncology
[1]。 Will radiation therapy be one of the standard therapies for oligometastatic kidney cancer? Or just around the corner.
background
The prognosis for metastatic kidney cancer is poor, with a 5-year survival rate of about 9.5%. Over the past 20 years, a better understanding of biology and the development of clinical research have made targeted molecular therapies the new standard for metastatic kidney cancer. Referring to the role of radiation therapy in metastatic kidney cancer, the protection of healthy tissues around tumor tissue has been significantly improved due to the increasing use of stereotactic radiation therapy (SRBT). In addition, radiation therapy plays a key role in palliative care of metastatic patients [2].
New precision imaging methods make it possible to differentiate oligometastatic kidney cancer (i.e., five or fewer metastatic lesions). However, the role of radiotherapy and systemic therapy in oligomettasis is unclear.
Based on this, the researchers conducted a prospective study to evaluate the feasibility of deterministic radiotherapy instead of systemic therapy for oligomettasis kidney cancer, and whether PFS can be prolonged and systemic therapy can be delayed.
method
This is a single-arm Phase II feasibility trial conducted at Anderson Cancer Center in the United States, which included < 5 metastatic lesions in ≥ 18-year-old patients with AN ECOG PS of 0 to 2, who had previously received up to one systemic treatment. After enrolling patients, stereotactic radiation therapy (defined as 5 ≤ sessions ≥7 Gy) is given to all lesions and maintained to systemic therapy. When lesion location prevents safe stereotactic radiation therapy, patients receive large-segment radiotherapy (60-70 Gy/10 or 52.5 to 67.5 Gy/15). The common primary endpoints are feasibility and PFS.
outcome
From 13 July 2018 to 18 September 2020, a total of 30 patients were enrolled, of whom 6 were women (20%). All patients were diagnosed with clear cell type heterochrystal oligometastatic kidney cancer and underwent nephrectomy prior to enlistment.
Table 1 Baseline features of patients
The researchers believe that radiation therapy is feasible because all patients have completed at least one round of radiation therapy, and unplanned < a 7-day delay in treatment. No patients reduced doses or discontinued due to adverse events. During the first round of radiation therapy, the most commonly treated sites are the lungs, followed by bones and lymph nodes.
Table 2 Radiotherapy characteristics
At a median follow-up of 17.5 months, 13 patients (43%) had disease progression, with a median PFS of 22.7 months and a 1-year PFS rate of 64%. Of these 13 patients, 1 patient had paraortic lymphatic outcome failure and had received radiotherapy (52.5 Gy/15 doses). In all other cases, disease progression is due to the development of new lesions, with a local control rate of 97% for radiotherapy and a 67% incidence of no new lesions at 12 months. At the end of the data cut-off, all patients were alive, with a 100% OS rate at 12 months.
Seven patients (23%) were initiated on systemic therapy, and the 1-year survival rate without systemic treatment was 82%.
Figure 1 PFS and survival without systemic treatment
Adjusted 1-year system-free treatment survival rate was 86%.
Fig. 2 Swimming chart of patient baseline and treatment characteristics, toxicity, and outcomes
Serious adverse events occurred in 3 (10%) patients: 2 and 1 patient had grade 3 (back pain and muscle weakness) and grade 4 (hyperglycemia) adverse events, respectively.
Discussion and conclusions
Sequential radiotherapy may help delay systemic therapy and may allow interruption of systemic therapy in patients with selective oligometastatic kidney cancer. To date, this is the first prospective clinical study of sequential local radiotherapy as a single treatment modality for the treatment of oligomettasis kidney cancer. The results suggest that sequential radiotherapy is a viable strategy for delaying systemic therapy, showing encouraging PFS and OS in patients with low tumor burden heterochronic oligometeroma kidney cancer who have previously undergone surgery. Large randomized controlled studies are needed to further evaluate efficacy in the future.
But there are still questions to be solved, one is, can prolonged systemic therapy be used as a good research endpoint? Second, there is no research data on radiation therapy combined with molecular therapy (synchronous or sequential), and until more data is available, the cornerstone of metastatic kidney cancer is still molecularly targeted therapy.
bibliography:
[1] Definitive radiotherapy in lieu of systemic therapy for oligometastatic renal cell carcinoma: a single-arm, single-centre, feasibility, phase 2 trial. ttps://doi.org/10.1016/ S1470-2045(21)00528-3
[2] oligometastatic renal cell carcinoma: radiotherapy as a new standard of care?