EAU 2024: Synchronous mHSPC: What are the Treatment Options and What Are the Goals of Treatment? What Is the Evidence for Surgery?

(UroToday.com) The 2024 European Association of Urology (EAU) annual congress held in Paris, France was host to a joint session of the EAU and the Advanced Prostate Cancer Consensus (APCCC). Professor Nicola Fossati discussed the current evidence for surgery in the treatment of patients with synchronous metastatic hormone-sensitive prostate cancer (mHSPC).

What is the rationale for cytoreductive radical prostatectomy? The ‘seed and soil’ hypothesis suggests that disease in the primary site acts as a nidus for metastatic deposits. As such, removing the prostate gland minimizes, in theory, additional micrometastatic shedding from the primary site. As the number of metastatic sites increases, the odds of a benefit for primary cytoreductive prostatectomy decrease given the ability of the individual metastatic deposits to each act a ‘nidus’ themselves. Thus, the focus of this topic should be among patients with oligometastatic disease.

An additional reason to consider cytoreductive radical prostatectomy is that patients undergoing PET-based imaging may have false-positive findings (i.e., PET demonstrates nodal disease, with underlying pathology negative for nodal involvement). In the 2021 study by Hope et al., 277 patients staged with PSMA PET underwent a radical prostatectomy with pelvic lymph node dissection. Of these 277 patients, 40 had evidence of nodal disease on imaging (i.e., miN+), of whom 10 had false positive findings with node negative disease on pathology. This suggests that the false positive rate of imaging may be as higher as 25% in this setting.1

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Do false positive findings extend to bone lesions as well? In a study by Kuten et al. in 2021, 406 patients underwent a radical prostatectomy at a single institution. Of these 406 patients, 15 (3.7%) had equivocal or highly suspicious bone lesions at PSMA PET imaging (27 total lesions). Of these 27 lesions, 24 were ultimately classified as negative for disease (i.e., false positive), as defined by post-operative PSA levels and radiologic follow-up.2

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What is the current evidence for cytoreductive radical prostatectomy? Professor Fossati noted that, to date, there are no randomized controlled trials in this space, and the largest studies have only included up to 116 patients. Notably, most of the studies of cytoreductive radical prostatectomy have utilized conventional imaging for staging purposes. Additionally, the majority (60 – 100%) of such patients received concomitant systemic therapy. 

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Recently, Rajwa et al. published the results of a multi-institutional analysis of 116 patients treated with cytoreductive nephrectomy at 13 European Centers.3 Oligometastatic prostate cancer was defined as miM1a and/or miM1b with ≤5 osseous metastases and/or miM1c with ≤3 lung lesions on PSMA-PET. Overall, 16%, 82%, and 2.6% of patients had miM1a, miM1b, and miM1c disease on imaging. With regards to peri-operative outcomes, the median estimated blood loss for these patients was 250 ml. 69% of patients did not experience any complications, with only 11% having grade two or worse complications. 5% of patients underwent re-operation, and the median hospital stay was 7 days.

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Functional outcomes appear to be similar to those of patients who undergo radical prostatectomy in the non-metastatic setting. One-year continence, defined as 0–1 pads/day, was achieved by 82% of patients in the cohort.3 

There is a concerted effort to prospectively evaluate the role of cytoreductive prostatectomy in these patients. Summarized below is a list of ongoing trials in this setting:

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Professor Fossati concluded as follows:

  • Cytoreductive radical prostatectomy is technically feasible
  • There are comparable peri-operative and functional outcomes for patients treated with locally advanced disease
  • The current level of evidence is low (ongoing clinical trials in this space)
  • Optimized patient selection is mandatory
  • The definition of the optimal multi-modal strategy remains uncertain

Presented by: Nicola Fossati, Department of Urology, Ospedale Regionale di Lugano, Civico USI - Università della Svizzera Italiana, Lugano, Switzerland 

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 European Association of Urology (EAU) annual congress, Paris, France, April 5th - April 8th, 2024 

References:

  1. Hope TA, Eiber M, Armstrong WR, et al. Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial. JAMA Oncol. 2021 Nov 1;7(11):1635-1642.
  2. Kuten J, Dekalo S, Mintz I, et al. The significance of equivocal bone findings in staging PSMA imaging in the preoperative setting: validation of the PSMA-RADS version 1.0. EJNMMI Res. 2021;11(1): 3.
  3. Rajwa P, Robesti D, Chaloupka M, et al. Outcomes of Cytoreductive Radical Prostatectomy for Oligometastatic Prostate Cancer on Prostate-specific Membrane Antigen Positron Emission Tomography: Results of a Multicenter European Study. Eur Urol Oncol. 2023: S2588-9311(23)00197-9.