EUROPEAN UROLOGY 67 (2015) 850–851
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority – Editorial Referring to the article published on pp. 839–849 of this issue
Salvage Lymph Node Dissection for Biochemical Recurrence Following Radical Prostatectomy: Is the Evidence There? Ofer Yossepowitch * Department of Urology, Rabin Medical Center, Petach-Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Early on, urologists were reluctant to offer surgery to men with high-risk prostate cancer (PCa). Those presumed to have extraprostatic disease based on the time-honored Partin tables were generally relegated to radiation therapy, not because the surgery was considered ineffective but because treating patients with urinary incontinence and impotence who were not cured of cancer was perceived as unattractive. Evidently, the practice of PCa has changed. Numerous studies are now available to substantiate the role of radical prostatectomy in managing high-risk PCa and to attest to its relative advantage over radiation therapy in this setting [1,2]. The inevitable consequence, however, is an increased proportion of surgically treated patients destined to oncologic failure. For some of these high-risk tumors, a postoperative rising prostate-specific antigen (PSA) level may indicate the presence of retained lymph node metastasis. With the understanding that metastatic PCa remains incurable, the quest for novel strategies that might improve clinical outcomes in these patients is germane. The elegant review by Abdollah and colleagues in this month’s issue of European Urology represents an example of the latter, addressing the merits of a highly controversial procedure: salvage lymph node dissection (SLND) in men with biochemical recurrence following radical prostatectomy whose cancer relapse is allegedly confined to the pelvic and retroperitoneal lymph nodes [3]. The importance of adequate lymph node dissection for diagnostic and, possibly, therapeutic purposes cannot be overstated; therefore, SLND should be regarded as a corollary of a suboptimal initial operation. At least in theory, the same suspicious lymph nodes could have been removed during prostatectomy. Moreover, although some men with microscopic nodal involvement may survive 10 yr
or longer after prostatectomy [4], whether we can truly cure metastatic PCa by using a surgical modality remains elusive. Short of a clinical trial, offering an additional operation to men who have been treated surgically for PCa and failed must be supported by robust data proving not only safety but also an unequivocal clinical advantage. In this distinct setting, the purported oncologic benefits must be carefully weighed against potential surgical morbidity as well as other available treatment alternatives. Salvage radical prostatectomy, for instance, has often been refuted by the urologic community at large [5], not because the surgery was considered more difficult compared with that for radiation-naı¨ve patients but because many felt the associated morbidity (rendering many patients incontinent) was unjustified if modifying the natural course of the disease favorably cannot be guaranteed. The merits of SLND should be analyzed in the same manner. Before considering its widespread adoption, three pertinent questions must be entertained: What is the clinical indication (to whom), what is the ultimate benefit to patients (why), and what should be the extent of dissection (how)? 1.
What is the clinical indication?
SLND has been advocated for patients with postprostatectomy-isolated pelvic and/or retroperitoneal lymph node relapse in the absence of additional metastatic deposits (eg, remote lymph nodes, bony or visceral metastasis). To select the appropriate candidates accordingly, the ideal diagnostic modality must have high (approaching 100%) positive predictive value to detect lymph node metastasis and high specificity to identify extralymphatic involvement. One should clearly avoid performing SLND to retrieve
DOI of original article: http://dx.doi.org/10.1016/j.eururo.2014.03.019. * Department of Urology, Rabin Medical Center – Beilinson, Petach-Tikva, 49100, Israel. Tel. +972 3 9376553; Fax: +972 3 9376569. E-mail address:
[email protected]. http://dx.doi.org/10.1016/j.eururo.2014.04.021 0302-2838/# 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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EUROPEAN UROLOGY 67 (2015) 850–851
reactive lymph nodes or offer the procedure to men who are likely to develop bone metastasis shortly after the operation. Do we possess the necessary tools to identify these patients? In their review, Abdollah and colleagues summarize the data addressing the utility of 11C-choline positron emission tomography/computed tomography (PET/CT) and diffusionweighted magnetic resonance imaging (MRI) in selecting patients for SLND. The limitations are substantial. First, there is a positive predictive value of 75–85% for 11C-choline PET/ CT, which translates into 15–25% of interventions being superfluous. Second, none of the available imaging modalities has proven sufficiently accurate in identifying microscopic bone involvement. Third, the reliability of MRI in detecting lymph node metastasis, while reassuring in general, has never been tested in a salvage setting, thus the likelihood of a false-positive or false-negative outcome in a region where lymph node dissection was performed requires further investigation. Fourth, the sensitivity of the aforementioned diagnostic modalities remains unknown because none of the patients with negative findings has undergone SLND. Clinical factors such as life expectancy, PSA level or PSA doubling time prior to intervention, and pathologic Gleason score may help refine the selection of patients but remain to be defined. Taken together, we clearly need to enhance our ability to choose the right candidates for SLND. Future advances in the use of ultrasmall superparamagnetic iron oxide particles to detect lymph node metastasis may provide us with the desirable solution [6].
had an initial ‘‘standard’’ lymph node dissection; in others, it may have been omitted (particularly if managed initially with a minimally invasive technique); and in some instances, the targeted nodal tissue may have been treated with radiation. Guiding the extent of dissection by imaging abnormities rather than using predetermined templates may theoretically reduce unwarranted morbidity but is justified only if the diagnostic tool has been proven to be perfectly accurate. Awaiting further data, the optimal technique for SLND will remain subject to individual biases and experience. In summary, SLND might represent a therapeutic option for very well-selected patients with moderately aggressive tumors (which remain to be defined) who had limited or no lymph node dissection during prostatectomy. Until its safety and efficacy have been better delineated by further studies, I believe SLND should be considered experimental and offered to patients in the setting of an approved clinical trial. Conflicts of interest: The author has nothing to disclose.
References [1] Zelefsky MJ, Eastham JA, Cronin AM, et al. Metastasis after radical prostatectomy or external beam radiotherapy for patients with clinically localized prostate cancer: a comparison of clinical cohorts adjusted for case mix. J Clin Oncol 2010;28:1508–13. [2] Sooriakumaran P, Nyberg T, Akre O, et al. Comparative effectiveness of radical prostatectomy and radiotherapy in prostate cancer: observational study of mortality outcomes. BMJ 2014;348:g1502.
2.
What is the clinical benefit?
[3] Abdollah F, Briganti A, Montorsi F, et al. Contemporary role of salvage lymphadenectomy in patients with recurrence following
The sought clinical benefit of SLND should be nothing short of improved survival. Interim end points such as PSA response rate and freedom from secondary interventions (postponing the use of adjuvant deprivation therapy) are important but remain limited. One study did demonstrate an encouraging complete PSA response following SLND alone in 30% of patients who were followed for a minimum of 5 yr [7]; however, the percentage of men who were treated with adjuvant hormonal therapy was not indicated and thus follow-up is warranted to determine whether SLND may truly affect the natural course of PCa. 3.
What should be the extent of dissection?
radical prostatectomy. Eur Urol 2015;67:839–49. [4] Abdollah F, Karnes RJ, Suardi N, et al. Predicting survival of patients with node-positive prostate cancer following multimodal treatment. Eur Urol 2014;65:554–62. [5] Tran H, Kwok J, Pickles T, Tyldesley S, Black PC. Underutilization of local salvage therapy after radiation therapy for prostate cancer. Urol Oncol 2014;32:701–6. [6] Birkhauser FD, Studer UE, Froehlich JM, et al. Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusionweighted magnetic resonance imaging facilitates detection of metastases in normal-sized pelvic lymph nodes of patients with bladder and prostate cancer. Eur Urol 2013;64:953–60. [7] Suardi N, Gandaglia G, Gallina A, et al. Long-term outcomes of salvage lymph node dissection for clinically recurrent prostate cancer: results of a single-institution series with a minimum follow-up of 5 years. Eur Urol 2015;67:299–309.
The topography of lymph node metastasis in PCa and the anatomic extent of dissection are matters of ongoing research. We no longer accept sampling of lymphatic tissue overlying the external iliac veins as adequate and uniformly agree that standard node dissection should comprise the external iliac, hypogastric, and obturator lymph nodes. A growing body of evidence indicates that the common iliac (up to the ureteral crossing or aortic bifurcation) and presacral nodes may also be involved [8]. Extending the boundaries of dissection to include the retroperitoneal nodes has also been reported [9,10], but its long-term benefit has never been supported by adequate data. Standardizing the extent of dissection in an SLND setting is even more challenging because some patients may have
[8] Heck MM, Retz M, Bandur M, et al. Topography of lymph node metastases in prostate cancer patients undergoing radical prostatectomy and extended lymphadenectomy: results of a combined molecular and histopathologic mapping study. Eur Urol 2014;66: 222–9. [9] Schiavina R, Concetti S, Brunocilla E, et al. First case of F-FACBC PET/CT-guided salvage retroperitoneal lymph node dissection for disease relapse after radical prostatectomy for prostate cancer and negative (11)C-choline PET/CT: new imaging techniques may expand pioneering approaches. Urol Int 2014;92:242–5. [10] Passoni NM, Suardi N, Abdollah F, et al. Utility of [11C]choline PET/CT in guiding lesion-targeted salvage therapies in patients with prostate cancer recurrence localized to a single lymph node at imaging: results from a 2014;32:38.e9–16.
pathologically validated series. Urol
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