PSMA-Radioguided Surgery in Localized Recurrent Prostate Cancer: Current and Future Aspects: Beyond the Abstract

Salvage therapy might be considered as a valid treatment option in selected prostate cancer patients experiencing biochemical failure after primary treatment – especially when they present in good performance status. It is crucial, however, that in these cases recurrent disease is detected early and reliably. Anatomical imaging (CT or MRI), but also positron emission tomography (PET) with currently most widely used tracers like radiolabeled choline-derivatives show severe limitations in this regard and often underestimate the extent of metastatic spread.

Recently, 68Gallium-labelled ligands of the prostate-specific membrane antigen (PSMA) that exhibit a significant overexpression of PSMA at the cell surface of most prostate cancer cells have been introduced in PET imaging of prostate cancer. These tracers made it possible to detect recurrencies even at low PSA values. However, detected suspicious lymph nodes are often small-sized and located atypically hindering surgical resection.

Thus, based on PSMA PET imaging we developed a novel method (PSMA-radioguided surgery) to radioactively label prostate cancer cells for detection during surgery. After preoperative injection of PSMA tracers that were labelled with γ-emitting isotopes like 111Indium or 99mTechnetium a gamma probe is used intraoperatively to localize the small unobtrusive and/or atypically located metastatic lymph nodes and to guide resection. First results show that PSMA-radioguided surgery is a sensitive and specific method to track suspicious lesions and to facilitate complete removal.

Follow-up data from 55 consecutive patients show a PSA reduction >50% and >90% in 44 (80%) and 29 (53%) patients, respectively. In 34 (62%) patients a complete biochemical response (PSA drop below 0.2ng/mL) was observed. 15 of 55 (27%) patients received further prostate cancer-specific treatment after median 110 days after PSMA-radioguided surgery (range: 48 – 454 days), the remaining 40 (73%) patients remained treatment-free at a median follow-up of 195 days (range: 43 – 591 days).

In summary, PSMA-RGS seems to be of high value in patients with localised prostate cancer recurrence since it allows exact localisation and resection of metastatic tissue using intraoperative as well as ex vivo gamma-probe measurements. Thus, this new salvage method has the potential to influence further disease progression positively. However, prerequisite for preoperative patient selection is – apart from clinical parameters – a PSMA PET scan with preferably only solitary soft tissue or lymph node recurrency. Greater patient cohorts as well as long-term follow-up are needed to confirm these initial, but encouraging results.

Written By: Tobias Maurer MD1, Isabel Rauscher MD2, Matthias Eiber MD2,3
1Department of Urology, Technical University of Munich, Munich, Germany
2Department of Nuclear Medicine, Technical University of Munich, Munich, Germany
3Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

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References:
Rauscher I, Eiber M, Jilg CA, Gschwend JE, Maurer T. [PSMA-radioguided surgery in localized recurrent prostate cancer : Current and future aspects]. Urologe A.  2016 Nov 24. [Epub ahead of print] German. PubMed PMID: 27885455. 

Rauscher I, Düwel C, Wirtz M, Schottelius M, Wester HJ, Schwamborn K, Haller B, Schwaiger M, Gschwend JE, Eiber M, Maurer T. Value of (111) In-prostate-specific membrane antigen (PSMA)-radioguided surgery for salvage lymphadenectomy in recurrent prostate cancer: correlation with histopathology and clinical follow-up. BJU Int. 2016 Nov 10. doi: 10.1111/bju.13713. [Epub ahead of  print] PubMed PMID: 27862863.   

Maurer T, Weirich G, Schottelius M, Weineisen M, Frisch B, Okur A, Kübler H, Thalgott M, Navab N, Schwaiger M, Wester HJ, Gschwend JE, Eiber M. Prostate-specific membrane antigen-radioguided surgery for metastatic lymph nodes in prostate cancer. Eur Urol. 2015 Sep;68(3):530-4. doi: 10.1016/j.eururo.2015.04.034. PubMed PMID: 25957851.   
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