MDT without ADT delays systemic therapy initiation in recurrent prostate cancer

In patients with solitary metastatic recurrences of prostate cancer, metastasis-directed therapy (MDT without androgen deprivation therapy (ADT) can lead to delayed initiation of systemic therapy, according to a study.

“Surgical MDT delayed median radiographic progression by nearly 15 months and median time to initiation of systematic therapy by 18 months,” the researchers said. “Stereotactic body radiation therapy (SBRT) delayed median radiographic progression by nearly 12 months and median time to initiation of systematic therapy by 17 months.”

Some 124 consecutive prostate cancer patients from 2008 to 2018 with a solitary oligorecurrent metastatic lesion on positron emission tomography imaging and who were treated with MDT without ADT were identified from the Mayo Clinic C-11 choline registry. MDT included either SBRT or surgical excision.

Of the patients, 67 underwent surgery (median follow-up 54 months) and 57 SBRT (median follow-up 53 months). Among those treated with surgery, 80.5 percent had >50-percent decline in prostate-specific antigen at first follow-up, and the rate of radiographic progression-free survival at 3 years was 29 percent. Median initiation of systemic therapy was 18.5 months. [J Urol 2022;208:1240-1249]

Among patients who underwent SBRT, 40.3 percent had >50-percent decline in prostate-specific antigen at first follow-up, and the rate of radiographic progression-free survival was 17 percent. Likewise, initiation of systemic therapy in this cohort had a median of 17.8 months.

“Surgical MDT was primarily utilized in patients with a solitary lymph node metastasis, while SBRT was used nearly exclusively for solitary bone metastasis. For this reason, we did not compare the two treatment modalities and instead present both as options in their own unique clinical scenarios,” the researchers said.

“While radiographic progression of disease was delayed in both surgical and SBRT cohorts, these results need to be interpreted separately as the natural history of lymph node and bone metastasis differ,” they added. [Front Oncol 2020;10(3446):627379]

Revision of guidelines

To date, MDT is not recommended as part of guideline-based care by both the American Urological Association and the National Comprehensive Cancer Network (NCCN). Recently, however, the NCCN has allowed the consideration of MDT to improve progression-free survival. [J Urol 2021;205:14-21; J Natl Compr Canc Netw 2019;17:479-505]

“Our report, along with upcoming clinical trials such as the STORM trial suggests a revision of the guidelines to allow for MDT in carefully selected patients,” the researchers said.

Traditionally, the standard of care was immediate or delayed ADT with biochemical or radiographic recurrence, irrespective of disease volume. Only recently has MDT with surgical resection or SBRT been considered as a management strategy in oligometastatic prostate cancer. [Eur Urol 2017;71:630-642; Eur Urol 2018;73:178-211; Eur Urol 2018;73:178-211]

“While the American Urological Association Guidelines don’t currently specify a role for MDT in metastatic castrate-sensitive prostate cancer, European Association of Urology guidelines allow for salvage lymph node dissection in lymph node only metastatic disease,” the researchers noted. [J Urol 2021;205:14-21; Eur Urol 2017;71:630-642]

“The benefits of MDT in oligometastatic disease include potential for a cure, avoidance of side effects from systemic therapy, and delayed time to castration resistance. Despite the suggestion that MDT may provide an oncologic benefit compared to standard ADT, this remains highly debated,” they added. [J Clin Oncol 2018;36:446-453; Eur Urol 2019;76:493-504]