Tag Archive for: aotw 10-07-19

Posts

Article of the week: 68Ga‐PSMA PET/CT predicts complete biochemical response from RP and lymph node dissection in intermediate‐ and high‐risk PCa

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this month, it should be this one.

Gallium‐68‐prostate‐specific membrane antigen (68Ga‐PSMA) positron emission tomography (PET)/computed tomography (CT) predicts complete biochemical response from radical prostatectomy and lymph node dissection in intermediate‐ and high‐risk prostate cancer

 

Pim J. van Leeuwen*, Maarten Donswijk, Rohan Nandurkar, Phillip Stricker§¶Bao Ho**, Stijn Heijmink††, Esther M.K. Wit*, Corinne Tillier*, Erik van Muilenkom*, Quoc Nguyen§, Henk G. van der Poel* and Louise Emmett§**

 

*Department of Urology, Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands, Faculty of Medicine, University of New South Wales Sydney, §The Australian Prostate Cancer Research Centre-NSW, The Garvan Institute of Medical Research, St Vincents Clinic, **Department of Theranostics and Nuclear Medicine, St Vincents Hospital Sydney, Sydney, New South Wales, Australia and ††Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

Abstract

Objective

To determine the value of gallium‐68‐prostate‐specific membrane antigen (68Ga‐PSMA)‐11 positron emission tomography (PET) /computed tomography (CT) in men with newly diagnosed prostate cancer.

Patients and methods

We analysed results of 140 men with intermediate‐ and high‐risk prostate cancer. All men underwent 68Ga‐PSMA‐11 PET/CT and multiparametric magnetic resonance imaging (mpMRI) before radical prostatectomy (RP) with extended pelvic lymph node (LN) dissection. For each patient, the clinical and pathological features were recorded. Prostate‐specific antigen (PSA) was documented at staging scan, and after RP, at a median (interquartile range) of 110 (49–132) days. A PSA level of ≥0.03 ng/mL was classified as biochemical persistence (BCP). Logistic regression was performed for association of clinical variables and BCP.

Results

In these 140 patients with intermediate‐ and high‐risk prostate cancer, 27.1% had PSMA PET/CT‐positive findings in the pelvic LNs. Sensitivity and specificity for detection of LN metastases were 53% and 88% (PSMA PET/CT) and 14% and 99% (mpMRI), respectively. The overall BCP rate was 25.7%. The BCP rate was 16.7% in men who were PSMA PET/CT LN‐negative compared to 50% in men who were PSMA PET/CT LN‐positive (P < 0.05). The presence of PSMA‐positive pelvic LNs was more predictive of BCP after RP than cT‐stage, PSA level, and the Gleason score, adjusted for surgical margins status.

Conclusions

68Ga‐PSMA‐11 PET/CT is highly predictive of BCP after RP, and should play an important role informing men with intermediate‐ or high‐risk prostate cancer.

 

Editorial: Preoperative PSMA‐targeted PET imaging: more than just a tool for prostate cancer staging?

The presence of lymph node metastases at the time of prostate cancer diagnosis has significant implications for treatment. According to current guidelines from the National Comprehensive Cancer Network, men with positive lymph nodes on initial staging imaging should be offered treatment with androgen deprivation (± abiraterone) along with consideration for external beam radiation therapy [1]. In contrast, men with clinically localised high‐ or very‐high‐risk prostate cancer have the option of undergoing radical prostatectomy. Unfortunately, currently available diagnostic imaging modalities (i.e. contrast‐enhanced CT and MRI) fall short in their ability to accurately identify lymph node metastases, which are often small and difficult to discern from other structures within the pelvis. Thus, there exists a conundrum: if we cannot accurately detect lymph node involvement, how can we appropriately manage it?

In this edition of the BJUI, Leeuwen et al. [2] report on the utility of molecular imaging with 68Ga‐PSMA‐11 positron emission tomography (PET)/CT in the preoperative staging of men with prostate cancer. To date, the greatest clinical utility of PSMA‐targeted PET has been in the management of men with biochemically recurrent prostate cancer [3]. In the present study by Leeuwen et al. [2], 140 patients with newly diagnosed intermediate‐ or high‐ risk prostate cancer underwent 68Ga‐PSMA‐11 PET/CT before radical prostatectomy with extended pelvic lymph node dissection. Surgical pathology served as the reference standard to which findings on 68Ga‐PSMA‐11 PET/CT were compared. In total, 27.1% of men were found to have radiotracer uptake in their pelvic lymph nodes, resulting in a sensitivity of 53% and a specificity of 88%. In contrast, multiparametric MRI had a sensitivity of only 14%, albeit with a higher specificity of 99%. These findings are in line with prior studies evaluating the diagnostic performance of PSMA‐targeted PET imaging for preoperative prostate cancer staging [4]. Of greater interest, however, is the authors’ observation that positivity on 68Ga‐PSMA‐11 PET/CT was strongly associated with postoperative PSA persistence (i.e. failure to cure). More specifically, after controlling for Gleason score, surgical margin status, and preoperative PSA level, positivity on PET/CT had an odds ratio of 5.87 (95% CI 1.30–26.59) for biochemical persistence. Furthermore, men with pN1 disease and a positive preoperative PET/CT (i.e. true positives) were over three times more likely to experience biochemical persistence than patients with pN1 disease and negative imaging (71.4% vs 21.4%). Thus, PSMA‐targeted PET not only stands to inform clinical staging, but also has the potential to offer independent prognostic information.

A future line of investigation is to explore the biological basis of the authors’ observation regarding PSMA as a prognostic marker. One explanation is that PET/CT identified men with higher volume lymph node metastases (a known prognostic factor), whilst patients with smaller more curable nodes were negative on imaging. After all, the authors state that the imaging test did not detect any pathologically positive lymph nodes <2 mm. Furthermore, only 27% of positive lymph nodes between 2 and 4 mm showed radiotracer uptake. Unfortunately, the authors did not account for differences in the volume of nodal metastases in their analysis. A second possible explanation for the authors’ observation is that PSMA is upregulated through the same signaling pathways that drive an aggressive prostate cancer phenotype, allowing for PSMA expression to provide prognostic information independent of tumour volume. Indeed, others have previously shown that PSMA expression, as measured by immunohistochemistry, corresponds with increasing tumour grade, stage and risk of biochemical failure [5]. Of course, these concepts are not mutually exclusive and further investigation is needed in order for PSMA‐targeted imaging to be rationally applied as a prognostic test.

References

  1. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer (Version 4.2018)2018. Accessed November 2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.
  2. Leeuwen, PJDonswijk, MNandurkar, R et al. Gallium‐68‐prostate‐specific membrane antigen (68Ga‐PSMA) positron emission tomography (PET)/computed tomography (CT) predicts complete biochemical response from radical prostatectomy and lymph node dissection in intermediate‐ and high‐risk prostate cancer. BJU Int 201912462– 8
  3. Han, SWoo, SKim, YJSuh, CHImpact of 68Ga‐PSMA PET on the management of patients with prostate cancer: a systematic review and meta‐analysis. Eur Urol 201874179– 90
  4. Gorin, MARowe, SPPatel, HD et al. Prostate specific membrane antigen targeted 18F‐DCFPyL positron emission tomography/computerized tomography for the preoperative staging of high risk prostate cancer: results of a prospective, phase II, single center study. J Urol 2018199126– 32
  5. Minner, SWittmer, CGraefen, M et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate 201171281– 8

 

© 2021 BJU International. All Rights Reserved.