SPECT-CT Guided Lymphatic Mapping and Sentinel Lymphadenectomy (LM/SL) in Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

SPECT-CT Guided Lymphatic Mapping and Sentinel Lymphadenectomy (LM/SL) in Prostate Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00773318
• Other study ID #: R-06-433
• Secondary ID: 12638
• Status: Terminated
• Phase: N/A
• First received: July 25, 2008
• Last updated: March 2, 2012
• Start date: April 2008
• Est. completion date: February 2012

Study information

• Verified date: March 2012
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

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%).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Procedure:
• SPECT/CT guided LM/SL
Detection, localization, and removal of sentinel lymph node (s) from prostate cancer guided by an integrated SPECT/low-dose multislice CT

Locations

Country	Name	City	State
Canada	University Hospital - Dpt. of Nuclear Medicine	London	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Lawson Health Research Institute	London Regional Cancer Program, Canada, University of Western Ontario, Canada

Country where clinical trial is conducted

Canada, 

References & Publications (10)

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. Epub 2005 Dec 9. — View Citation

de Bonilla-Damiá A, Roberto Brouwer O, Meinhardt W, Valdés-Olmos RA. Lymphatic drainage in prostate carcinoma assessed by lymphoscintigraphy and SPECT/CT: its importance for the sentinel node procedure. Rev Esp Med Nucl Imagen Mol. 2012 Mar-Apr;31(2):66-70. doi: 10.1016/j.remn.2011.09.003. Epub 2011 Nov 3. — View Citation

Kizu H, Takayama T, Fukuda M, Egawa M, Tsushima H, Yamada M, Ichiyanagi K, Yokoyama K, Onoguchi M, Tonami N. Fusion of SPECT and multidetector CT images for accurate localization of pelvic sentinel lymph nodes in prostate cancer patients. J Nucl Med Technol. 2005 Jun;33(2):78-82. — View Citation

Krengli M, Ballarè A, Cannillo B, Rudoni M, Kocjancic E, Loi G, Brambilla M, Inglese E, Frea B. Potential advantage of studying the lymphatic drainage by sentinel node technique and SPECT-CT image fusion for pelvic irradiation of prostate cancer. Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):1100-4. Epub 2006 Sep 11. — View Citation

Rousseau C, Rousseau T, Bridji B, Pallardy A, Lacoste J, Campion L, Testard A, Aillet G, Mouaden A, Curtet C, Kraeber-Bodéré F. Laparoscopic sentinel lymph node (SLN) versus extensive pelvic dissection for clinically localized prostate carcinoma. Eur J Nucl Med Mol Imaging. 2012 Feb;39(2):291-9. doi: 10.1007/s00259-011-1975-x. Epub 2011 Nov 16. — View Citation

Scardino P. Update: NCCN prostate cancer Clinical Practice Guidelines. J Natl Compr Canc Netw. 2005 Nov;3 Suppl 1:S29-33. — View Citation

Schumacher MC, Burkhard FC, Thalmann GN, Fleischmann A, Studer UE. Is pelvic lymph node dissection necessary in patients with a serum PSA<10ng/ml undergoing radical prostatectomy for prostate cancer? Eur Urol. 2006 Aug;50(2):272-9. Epub 2006 Feb 28. — View Citation

Vermeeren L, Valdés Olmos RA, Meinhardt W, Bex A, van der Poel HG, Vogel WV, Sivro F, Hoefnagel CA, Horenblas S. Value of SPECT/CT for detection and anatomic localization of sentinel lymph nodes before laparoscopic sentinel node lymphadenectomy in prostate carcinoma. J Nucl Med. 2009 Jun;50(6):865-70. doi: 10.2967/jnumed.108.060673. Epub 2009 May 14. — View Citation

Weckermann D, Dorn R, Trefz M, Wagner T, Wawroschek F, Harzmann R. Sentinel lymph node dissection for prostate cancer: experience with more than 1,000 patients. J Urol. 2007 Mar;177(3):916-20. — View Citation

Weckermann D, Goppelt M, Dorn R, Wawroschek F, Harzmann R. Incidence of positive pelvic lymph nodes in patients with prostate cancer, a prostate-specific antigen (PSA) level of < or =10 ng/mL and biopsy Gleason score of < or =6, and their influence on PSA progression-free survival after radical prostatectomy. BJU Int. 2006 Jun;97(6):1173-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Technical feasibility and clinical utility of LM/SL with SPECT/CT in patients with early stage prostate cancer versus CLND.		1 year - 2 years	Yes
Secondary	Tolerability, operating time, and complications rate of SPECT/CT guided LM/SL		1 year - 2 years	Yes

External Links

•   Lawson Health Research Institute
•   The University of Western Ontario