Feasibility and safety of radical prostatectomy for oligo‐metastatic prostate cancer: the Testing Radical prostatectomy in men with prostate cancer and oligo‐Metastases to the bone (TRoMbone) trial

Abstract

Objectives To test the feasibility of randomisation to radical prostatectomy (RP) plus pelvic lymphadenectomy in addition to standard‐of‐care (SOC) systemic therapy in men with newly diagnosed oligo‐metastatic prostate cancer. Patients and Methods A prospective, randomised, non‐blinded, feasibility clinical trial with an embedded QuinteT Recruitment Intervention (QRI) to optimise recruitment was conducted in nine nationwide tertiary care centres undertaking high‐volume robotic surgery. We aimed to randomise 50 men with synchronous oligo‐metastatic prostate cancer within an 18‐month recruitment period to SOC systemic therapy vs SOC plus RP (intervention arm). The main outcome measures were: ability to randomise patients, optimised by a QRI; EuroQoL five Dimensions five Levels (EQ‐5D‐5L) questionnaires to capture quality‐of‐life (QoL) data at baseline and 3 months post‐randomisation; routine clinicopathological assessment to capture adverse events and prostate‐specific antigen in both arms, plus standard perioperative parameters in the surgical arm. Results A total of 51 men were randomised within 14 months (one was subsequently deemed ineligible), with 60–83% accrual rate in centres that recruited at least two patients. All patients completed the trial follow‐up; one patient in the intervention arm subsequently did not undergo the surgical intervention and one in the SOC arm refused all therapies. The QRI positively impacted recruitment. QoL data showed similarly high functioning in both study arms. Surgery for men with oligo‐metastatic prostate cancer was found to be safe and had similar impact on early functional outcomes as surgery for standard indication. Conclusion It is feasible to randomise men with synchronous oligo‐metastatic prostate cancer to a surgical intervention in addition to standard systemic therapies. While surgery appeared safe with no substantial impact on QoL in this feasibility study, a large randomised controlled trial is now warranted to examine treatment effectiveness of this additional component in the multimodality management of oligo‐metastatic prostate cancer.

The current role of precision surgery in oligometastatic prostate cancer

“… 56 Overall, perioperative complication rates for CRP ranged between 12% and 34%. 60 , 67 , 68 , 72 Comparing CRP to RPx in nonmetastatic PCa in a population-based cohort, CRP was associated with slightly higher overall complication rates (14.9% versus 12.3%), but the inherent limitations of population-based databases were a bias. 73 In a retrospective study that assessed perioperative outcomes in patients undergoing robot-assisted CRP for omPCa, 5.3% of the men experienced Clavien–Dindo classification (CDC) grade III complications but no grade IV or grade V complications.…”

“…Recently, the TRoMbone trial successfully randomized 51 patients with newly diagnosed omPCa to CRP plus SOC versus SOC (ADT ± docetaxel) alone. 72 The study showed that it is feasible to randomize patients with de novo omHSPC to a surgical intervention providing the groundwork for larger trials. 72 In addition, there was no difference in the QOL between the two groups confirming the results of retrospective studies that did not find a significant difference in QOL outcomes in men undergoing CRP compared to men with localized PCa at the time of surgery.…”

“…Several retrospective studies and the Testing Radical prostatectomy in men with prostate cancer and oligoMetastases to the bone (TRoMbone) trial showed that open and robot-assisted CRP were technically feasible in omPCa. 60 , 67 , 68 , 72 In the TRoMbone trial, all surgeries were carried out robot-assisted and completed without conversion. 72 The 90-day complication rate after CRP in the study by Sooriakumaran et al .…”

“… 60 , 67 , 68 , 72 In the TRoMbone trial, all surgeries were carried out robot-assisted and completed without conversion. 72 The 90-day complication rate after CRP in the study by Sooriakumaran et al . was 20.8%.…”

Defining Oligometastatic Disease in the New Era of PSMA-PET Imaging for Primary Staging of Prostate Cancer

“…As with many critical clinical trials that have taken place before the widespread use of emerging PET radiotracers for prostate cancer staging, these definitions rely primarily on findings as seen on CT, MRI, and 99m Tc-methyl diphosphonate (MDP) skeletal scintigraphy. Through these trials (and others, including the STAMPEDE and HORRAD trials), many important conclusions were made regarding the prognosis and treatment of patients with oligometastatic prostate cancer at the time, often utilizing a combination of systemic therapy, targeted radiotherapy, and/or surgical resection with varying definitions of oligometastatic disease [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. However, as the utilization of PET-based molecular imaging for prostate cancer staging has increased, there is increasing uncertainty on how to apply the conclusions of these important clinical trials, performed in the past relying on conventional staging imaging modalities to disease detected through higher sensitivity, more novel PET imaging.…”