Accuracy of lymph node imaging in prostate cancer: A prospective cohort study to determine the concordance between two imaging modalities, *Combidex* magnetic resonance imaging (Nano MRI) and 68Ga-PSMA positron emission tomography (PET).

Following curative intended therapy in prostate cancer patients, a high
proportion of patients (approx. 25%) relapse with local and/or distant
recurrence [1]. The metastasis of a lymph node (LN) in a patient with prostate
cancer means that the disease has become systemic with the increased risk of
disease progression. Therefore the ability to detect the presence of LN
metastasis is important in terms of disease prognosis and treatment options. In
the past, patients with LN metastasis have had poor prognoses due to the
scarcity of accurate staging techniques and toxic treatment regimens such as
radiotherapy. For those patients with a medium to high risk of having LN
metastasis, the current procedure is a bilateral pelvic lymph node dissection
(PLND). This is the standard procedure prior to curative treatment with either
radical prostatectomy or radiation therapy. However, the procedure is not
optimal due to the frequent inability to remove all positive lymph nodes within
the dissection area. 41% of metastatic LN disease is not found [2], due to
these LN being outside the routine surgery field. As a result, some urologists
will perform an extended lymphadenectomy (e-PLND), which leads to extended
operating times and the risk of complications [3]. Also, therapy of LN
metastases has limitations: more than 50% of metastatic LN are outside the
routine (RTOG-CTV) radiation field [4]. Thus the effect of standard LN
radiotherapy is limited [5]. Currently used imaging techniques such as CT and
conventional MRI are also not sensitive enough to detect prostate cancer
metastases due to the small size of the nodes (< 8mm) [6]. Finally, 11C-Choline
PET/CT fails to detect metastatic LN, when they are smaller than 6 mm [7] since
a minimum amount of tracer needs to be present in the LN to be detected.

However, patients with metastatic LN *8 mm have a significantly better 5-year
distant metastases-free (79% vs 16%) and overall survival (81% vs 36%), than
patients with larger positive lymph nodes [8]. Thus detection and localization
of most small LN and subsequent focused, patient tailored treatment of these
small metastatic LN may reduce side effects and enable cure [9-10].

An accurate non-invasive imaging modality in combination with existing
treatment techniques, may lead to a therapeutic shift for patients who have in
the past been restricted to palliative treatment. Recently developed imaging
modalities to detect small lymph node metastases, which offer promise, include
Nano Magnetic Resonance (Combidex) Lymphography (Nano MRL) and
68Gallium-Prostate Specific Membrane Antigen (PSMA) Positron Emission
Tomography Imaging (68Ga-PSMA PET).

1. To compare the following imaging technologies to the current practice of
histology of pelvic lymph node dissection:
a. PSMAGa68 PET
b. Nano MR Lymphography and an enhanced arterial map (Nano MRL / EAM) to locate
the position of the lymph nodes

2. Determine whether CONCORDANCE of these two imaging technologies (PSMAGa68
PET - functional imaging, and Nano MR - anatomical imaging) is worse, better or
equal to lymph-node dissection, the current gold standard

This study will be a prospective, one arm, non-randomised cohort study,
conducted at the Radboud University Medical Centre, Nijmegen, NL.

See paragraph E9. The nature and extent of the risks for participation in this
study according to the 'Normenkader' (NFU) is supposed to be negligible.