Androgen deprivation therapy (ADT) is historically the standard of care for patients with oligorecurrent, hormone-sensitive prostate cancer — a setting where a small number of metastases emerge at some point following local treatment of the primary tumor. However, many men opt to postpone ADT due to substantial side effects of the therapy, and there is an unmet need for alternative therapeutic approaches that preserve patients’ quality of life while deferring systemic treatment.

A new wave of imaging technologies now allows for the direct detection of oligometastases and removal through local ablative techniques such as stereotactic body radiotherapy (SBRT); some of these technologies are emerging as new metastasis-directed therapies (MDTs) for patients with prostate cancer.

Indeed, a small number of prospective studies investigating the use of MDT — mostly SBRT — in men with oligorecurrent disease have suggested that the treatment is safe, and in 1 study, up to 50% of patients did not require ADT or other forms of systemic treatment for 2 years following MDT.1 Such findings have led to the idea that MDT could serve as an intermediate treatment between surveillance and systemic ADT.

While clinical trials are still investigating the long-term survival benefits of conducting upfront MDT prior to standard-of-care systemic therapy, a recent study estimated the cost-effectiveness of such a treatment approach and compared it to 2 hypothetical systemic approaches — ADT alone, or combining more advanced hormone therapies with ADT.2


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Computational cost-effectiveness models suggested that at 10 years, upfront MDT followed by standard-of-care systemic therapy was similarly cost-effective as the other treatment approaches, suggesting that it could be a viable treatment strategy, particularly for patients who wish to defer systemic therapy. The findings were published in the International Journal of Radiation Oncology, Biology, Physics.

“Sometimes we think using fancy radiation is just adding cost, but it might actually be cost-effective if we are delaying the onset of more expensive other drugs,” said Amar U. Kishan, MD, an assistant professor and vice chair of clinical and translational research for the department of radiation oncology at the David Geffen School of Medicine at the University of California, Los Angeles, and a coauthor of the study.

In the study, Dr Kishan and his colleagues compared 3 hypothetical treatment strategies. In the first, patients with oligorecurrent, hormone-sensitive disease were to receive upfront SBRT, and upon progression, antihormonal drugs abiraterone acetate plus prednisone (AAP) together with ADT, followed by docetaxel chemotherapy plus ADT — combination approaches that have been associated with survival benefits in patients with de novo diagnoses of metastatic hormone-sensitive prostate cancer.3,4 In the second treatment scenario, patients received upfront AAP with ADT, followed by salvage docetaxel plus ADT. The third strategy entailed upfront treatment with docetaxcel plus ADT followed by salvage abiraterone plus ADT.

The team used Markov modeling to simulate how patients on each of these 3 treatments would progress through different health states over time — based largely on data from randomized clinical studies — and to predict the cost-effectiveness of each series of treatment at 10 years, including the costs of follow-up visits and diagnostic test imaging, in addition to the costs of the treatments themselves.

Probabilistic sensitivity analysis — whereby simulations were repeated 1 million times while varying model parameters to better reflect the variability in a real patient population — revealed that upfront MDT followed by systemic therapy was the most cost-effective strategy in nearly 54% of simulations. Total cost estimates for this approach ranged from $76,000 to $180,000, compared with ranges of $124,000 to $224,000 for the second approach, and $103,000 to $181,000 for the third approach.

Dr Kishan and his colleagues chose the now-generic drug abiraterone as an advanced therapy in their model, whereas other advanced agents, such as enzalutamide or apalutamide, would produce different results. If those had been employed instead of abiraterone in the study, upfront MDT may potentially appear even more cost-effective than the results suggested, they wrote.

The paper is “very provocative” in that it examines how different treatment approaches could potentially preserve oncologic outcomes, said Jennifer Cullen, PhD, MPH, associate director for cancer population sciences at the Case Comprehensive Cancer Center in Cleveland, Ohio, who wasn’t involved in the research. “It’s really being thoughtful about [whether] we are really preserving meaningful quantity of life, while we’re certainly causing declining quality of life.”

However, trials are needed before these findings can be adopted into practice, she added. “Because it’s based on modeling, and not actual observation of patients or randomized clinical trial data, I would be hesitant to get too excited and adopt this as the new thinking,” she added. Limitations of the study acknowledged by the authors included, for instance, uncertainties around whether trial data from patients with de novo metastatic disease would apply to patients with oligorecurrent disease, and various assumptions, such as assuming that all patients whose disease did not respond to systemic therapy would have similar outcomes irrespective of the prior treatments they had received.

Whether upfront MDT actually improves long-term survival outcomes and causes a meaningful delay in disease progression still needs to be studied in clinical trials, Dr Kishan said. “Is there a penalty someone would incur because they delayed these [systemic] drugs? Would those patients do worse, because they started these drugs later?,” he asked. “The converse is also true: we don’t know if there might be a meaningful benefit to doing this type of treatment, and maybe delaying the need to use 1 of these advanced drugs and maybe extending the time that that drug could be effective. From an effectiveness-against-the-cancer standpoint, [our study] is quite preliminary.”

Disclosure: Some of the investigators disclosed various financial ties to the pharmaceutical industry in this study. For a full list of disclosures, please refer to the original paper.

References

  1. Bowden P, See AW, Frydenberg M et al. Fractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: interim outcomes of a prospective clinical trial. Int J Cancer. 2020;146(1):161-168.
  2. Parikh NR, Chang EM, Nickols NG et al. Cost-effectiveness of metastasis-directed therapy in oligorecurrent hormone-sensitive prostate cancer [published online January 13, 2020]. Int J Radiat Oncol Biol Phys. doi: 10.1016/j.ijrobp.2020.06.009
  3. Clarke NW, Ali A, Ingleby FC et al. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019;30(12):1992-2003.
  4. Hoyle AP, Ali A, James ND et al. Abiraterone in “high-“ and “low-risk” metastatic hormone-sensitive prostate cancer. Eur Urol. 2019;76(6):719-728.

This article originally appeared on Cancer Therapy Advisor