Clinical trial NCT00773318: SPECT-CT Guided Lymphatic Mapping and Sentinel Lymphadenectomy (LM/SL) in Prostate Cancer
Official title: SPECT-CT Guided Lymphatic Mapping and Sentinel Lymphadenectomy (LM/SL) in Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Prostate Cancer
Keywords: LM/SL
SPECT/low-dose multislice CT
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: London Regional Cancer Program, Canada
name: University of Western Ontario, Canada
First posted: 2008-10-16
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Nodal staging is a key-step in pre-treatment assessment of prostate cancer. In patients with a low probability of nodal metastasis, bilateral pelvic lymphadenectomy is controversial. The large majority of them (\> 80%) are free of nodal disease in obturator and external iliac stations. On the other hand, skip metastases located outside the standard lymphadenectomy may be missed, particularly in more proximal nodal stations (i.e. common iliac nodes and pre-sacral nodes).

In prostate cancer, growing data indicate the potential utility of LM/SL, particularly in patients with a low pre-test probability of nodal disease. However, very few data have been reported on the feasibility and the utility of SPECT/CT following LM/SL. In a pilot study including 11 patients with prostate cancer, Kizu and colleagues used a software image fusion from separate SPECT and CT studies. These authors concluded to the utility of image fusion to localize anatomically the SLNs. They also suggested the use of hardware fusion from a single gantry SPECT/CT device for accurate detection of SLNs. Accordingly, Corvin and colleagues recently reported the suitability of sentinel node detection in a series of 28 patients with prostate cancer; in this study, an integrated single slice SPECT/CT device was used to localize the SLNs.

In the light of the encouraging data from literature and our own preliminary clinical experience, we hypothesized that the use of integrated SPECT/low-dose multislice CT guided LM/SL may be of clinical interest in patients with prostate cancer.

Detailed description: A multidisciplinary team (urologist, oncologist, radiologist, pathologist, and nuclear medicine) will assess the technical feasibility of LM/SL with SPECT/CT as well as its clinical potential for the staging of regional lymph nodes in 30 consecutive patients with AJCC stages I-II-III prostate cancer scheduled for prostatectomy and pelvic lymph node dissection according to the standards of care.

This is a 2-day protocol with a single isotopic tracer (Tc99m-cysteine rhenium colloids, 10-15 nm). The tracer injections will be performed under trans-rectal ultra-sound guidance (1 inj/lobe, 74MBq, 0.2 cc).

The first day or injection day (D0), an early imaging session with planar acquisitions (anterior and posterior views) will be performed within 30 min post-tracer injection. A delayed imaging session with planar and SPECT/CT acquisitions will be also performed 1 to 3 hours after tracer injection. The SPECT/CT device to be used in this research protocol is the Infinia Hawkeye 4-slice from GE Healthcare. This hybrid camera incorporates a low-dose CT with a 2.5 mA current (eff.dose \< 2mSv) on a dual-head gamma camera. SPECT/CT data will be analysed on the Xeleris 2.05v (Volumetrix for Hawkeye Oncology).

The second day (D+1 post-tracer injection), all prostate cancer patients will undergo a radical prostatectomy with complete pelvic lymph node dissection (CLND). Sentinel lymph nodes (SLNs) will be detected intra-operatively by using a gamma probe (Navigator, Tyco Healthcare). In this single tracer study, SLNs are defined as hot nodes only including the hottest node and any hot node ≥ 10% of the hottest node. In this SPECT/CT protocol, additional non-radioactive nodes eventually detected on the CT component and suspicious of tumor involvement (lymphadenopathies \> 1cm) will be also removed, especially lymph nodes located in unpredictable lymphatic basins. Surgery will be performed by the same surgeons.

SLNs and non-SLNs will be analyzed by the same pathologist. For SLNs, a Hematoxylin \& Eosin staining (H-E) will be firstly performed. If negative, 3 more H-E stains levels will be performed and immuno-peroxidase stains for Cytokeratins AE1/AE3, PSA, and PAP. Non-SLNs will be analyzed according to the routine protocol with 3 H-E stained levels only. The SLN features will be noted: number, anatomical localization in vivo, counting rates ex vivo. The pathological characteristics of metastatic SLNs and non-SLNs will be precisely recorded: size, involvement (micro-metastases ≤ 2mm; macro-metastases; isolated tumor cells), % of nodes involved (small \< 25%; moderate = 25-75%; massive \> 75%).

Eligibility criteria: Inclusion Criteria:

* Patients with histologically proven prostate cancer
* Initial staging (Bone scan, CT, or MRI) according to the NCCN guidelines
* Patients with AJCC stages I - II - III prostate cancer including men with clinical T3N0M0 disease, men with PSA \> 10 mg/ml, and men with Gleason score of 8-10 (high grade disease)
* Prostate cancer patients will be scheduled for prostatectomy and pelvic lymph node dissection
* Informed consent signed by the patient

Exclusion Criteria:

* Patients with no histological evidence of prostate cancer
* Patient with regionally advanced disease or metastatic disease (T4, and/or N1, and/or M1)
* Patients with clinically and/or radiologically evident regional lymph node metastases
* Patients who are not scheduled for radical prostatectomy and pelvic lymph node dissection
* Patients with physical and/or psychological contraindications
* Recent studies in Nuclear Medicine with long half-time isotopes (i.e. T ½ \> 48h; 111In, 67Ga, 201Tl, 131I) performed within 1 week preceding the LM/SL

Primary outcomes:
measure: Technical feasibility and clinical utility of LM/SL with SPECT/CT in patients with early stage prostate cancer versus CLND.
timeFrame: 1 year - 2 years
Secondary outcomes:
measure: Tolerability, operating time, and complications rate of SPECT/CT guided LM/SL
timeFrame: 1 year - 2 years
Other outcomes:
Locations:
city: London
country: Canada
facility: University Hospital - Dpt. of Nuclear Medicine
state: Ontario
Study officials:
affiliation: The University of Western Ontario- Nuclear Medicine
name: Irina Rachinsky, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Western Ontario - Nuclear Medicine
name: Albert Driedger, MD, PhD
role: STUDY_CHAIR
affiliation: The University of Western Ontario- Urology
name: Joseph Chin, MD, PhD
role: STUDY_DIRECTOR
affiliation: The University of Western Ontario - Pathology
name: Madeleine Moussa, MD
role: STUDY_DIRECTOR
References:
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citation: Corvin S, Schilling D, Eichhorn K, Hundt I, Hennenlotter J, Anastasiadis AG, Kuczyk M, Bares R, Stenzl A. Laparoscopic sentinel lymph node dissection--a novel technique for the staging of prostate cancer. Eur Urol. 2006 Feb;49(2):280-5. doi: 10.1016/j.eururo.2005.08.021. Epub 2005 Dec 9.
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