Although several prominent randomized clinical trials have revolutionized the use of local therapy in so-called oligometastatic patients, data regarding long-term outcomes remain to be defined. Additionally, the refinement of these clinical strategies specific to each histology may ultimately be necessary given that the underlying disease biology may affect clinical responses to oligometastasis-directed therapy.

In that context, the current clinical trial sought to evaluate hormone therapy and local metastasis-directed therapy to oligometastatic prostate cancer. This prospective study treated 29 patients with fractionated radiotherapy and ADT. About half the subjects had de novo oligometastatic disease and half had oligorecurrence. Over a 10-year median follow-up, PFS was approximately 2 years. However, ~60% of patients had durable local control of the treated lesions at last follow-up. De novo metastatic patients did better than oligorecurrent patients, suggesting different biology between the 2 disease states.

Overall, rather than being groundbreaking itself, this study fits as an orthogonal validation to larger studies showing the benefit of local therapy in oligometastatic patients.

Reference (Pub-Med Link): Hao, C., Ladbury, C., Lyou, Y., Manoukian, S., et al. (2022). Long-Term Outcomes of Patients on a Phase II Prospective Trial of Oligometastatic  Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation and External Beam Radiation. International Journal of Radiation Oncology, Biology, Physics, 114(4), 705–710. https://doi.org/10.1016/j.ijrobp.2022.06.085

Key Institution: City of Hope, Los Angeles, CA

Keywords: Oligometastases, Prostate

This is a prospective single-arm phase 2 study conducted at 8 US medical centers enrolling men 50 years of age and older with biopsy confirmed, unilateral, MRI-visible, intermediate risk, treatment naïve, primary prostate adenocarcinoma. Patients were treated with MRI-guided focused ultrasound. The co-primary endpoints were oncological outcomes (absence of GG2+ and higher cancer at 6- and 24-months after treatment) and safety (AEs up to 24 months after treatment). At 2 years, 88% of men had no evidence of GG2+ prostate cancer in the treated area. 60% had no evidence of GG2+ disease in the whole-gland on biopsy at 24 months. There were no G4/5 AEs reported. There was one grade 3 UTI reported. This study demonstrates that partial gland, focused US can be used to treat carefully selected men with intermediate risk prostate cancer with an acceptable side effect profile. However, the high rates of progression in the untreated areas of the prostate cast doubt on the utility of this approach. Nevertheless, this can be presented in the “T” area of a SWOT analysis for prostate cancer radiotherapy.

Reference (Pub-Med Link): Ehdaie, B., Tempany, C. M., Holland, F., et al.  (2022). MRI-guided focused ultrasound focal therapy for patients with intermediate-risk prostate cancer: a phase 2b, multicentre study. The Lancet. Oncology, 23(7), 910–918. https://doi.org/10.1016/S1470-2045(22)00251-0

Key Institution: Multi-institutional, USA

Keywords: Prostate

This is a retrospective patterns of care study of 352 randomly selected patient records of patients with ALK+ NSCLC on 1st-line ALK inhibitor monotherapy. The primary outcome was brain-directed local treatment within 4 months. Of the 352 patients, 146 had brain metastases. 104/146 received CNS-directed local therapy, predominantly RT alone. SRS monotherapy was more common than WBRT monotherapy (53% vs 39%). Multivariable analysis demonstrated that patients who had their first brain metastasis during or after 2017 had a decreased rate of receiving brain directed therapy, adjusted incidence ratio of 0.63 (95% CI: 0.41 – 0.95, p=0.026). There was no change in the proportion receiving SRS vs WBRT. This study demonstrates a decreasing use of CNS directed therapy for patients with NSCLC brain metastasis on first line ALK inhibitors. This study provides evidence in support of general observations that the use of radiotherapy for brain metastases is declining with the advent of systemic agents with increasing intracranial activity. It remains to be seen, however, which patients are most appropriate for this approach.

(Open Access)

Reference (Pub-Med Link): Kumar, S., Wang, X., Pittell, H., Calip, G. S., Weiss, S. E., Meyer, J. E., & Royce, T. J. (2022). Real-world Use of Radiation for Newly Diagnosed Brain Metastases in Patients With ALK-positive Lung Cancer Receiving First-line ALK Inhibitor. International Journal of Radiation Oncology, Biology, Physics, 114(4), 627–634. https://doi.org/10.1016/j.ijrobp.2022.07.010

Key Institution: Multi-institutional, USA

Keywords: Brain, Metastasis

This trial was a randomized, multicenter, phase 3 trial that included patients with a persistently detectable or initially undetectable and rising PSA of between 0.1 and 2.0 after prostatectomy. Patients had pT2 or pT3 disease, Gleason score of 9 or less, and good performance status. These patients were randomized to prostate bed radiation therapy to 64.8 Gy-70.2 Gy at 1.8 Gy per fraction daily alone, or the same regimen plus short-term ADT or prostate bed radiation plus lymph node radiation to 45 Gy at 1.8 Gy per fraction and then a cone down to the PTV for 19.8-25.2 Gy plus ADT.

Authors looked at a primary end point of freedom from progression, defined as biochemical failure per the Phoenix definition, clinical failure, or death. 1716 were eligible for the final evaluation and at the interim analysis, the Haybittle-Peto boundary for 5-year freedom from progression was exceeded when group 1 was compared with group 3 (p<0.0001). The difference between groups 2 and 3 did not exceed the boundary (p=0·0063). The 5-year freedom from progression rates in all patients were 70.9%, 81.3%, and 87.4% in groups 1, 2, and 3 respectively. Adverse events were more common in group 3, but late toxicities were similar between the three groups.

The authors conclude that the addition of ADT to salvage prostate bed radiation improves outcomes, and the addition of pelvic lymph node irradiation further improves outcomes without any significant differences in late toxicities.

Reference (Pub-Med Link): Pollack, A., Karrison, T. G., Balogh, A. G., et al. (2022). The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial. Lancet (London, England), 399(10338), 1886–1901. https://doi.org/10.1016/S0140-6736(21)01790-6

Key Institution: Multi-Center, International

Keywords: Prostate