Carlo A Bravi1, Nicola Fossati1, Giorgio Gandaglia1, Nazareno Suardi2, Elio Mazzone1, Daniele Robesti1, Daniar Osmonov3, Klaus-Peter Juenemann3, Luca Boeri4, R Jeffrey Karnes5, Alexander Kretschmer6, Alexander Buchner6, Christian Stief6, Andreas Hiester7, Alessandro Nini8, Peter Albers7, Gaëtan Devos9, Steven Joniau9, Hendrik Van Poppel9, Shahrokh F Shariat10, Axel Heidenreich11, David Pfister11, Derya Tilki12, Markus Graefen12, Inderbir S Gill13, Alexander Mottrie14, Pierre I Karakiewicz15, Francesco Montorsi1, Alberto Briganti16. 1. Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. 2. Department of Urology, Policlinico San Martino Hospital, University of Genova, Genova, Italy. 3. Department of Urology and Pediatric Urology, University Hospital Schleswig Holstein, Campus Kiel, Germany. 4. Department of Urology, Mayo Clinic, Rochester, MN, USA; Department of Urology, IRCCS Foundation Ca Granda, Maggiore Policlinico Hospital, University of Milan, Milan, Italy. 5. Department of Urology, Mayo Clinic, Rochester, MN, USA. 6. Department of Urology, Ludwig-Maximilians University, Munich, Germany. 7. Department of Urology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany. 8. Department of Urology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Department of Urology and Pediatric Urology, Saarland University Medical Center, Saarland University, Homburg, Germany. 9. Department of Urology, University Hospitals Leuven, Leuven, Belgium. 10. Department of Urology, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. 11. Department of Urology, University of Cologne, Cologne, Germany. 12. Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany. 13. USC Institute of Urology, University of Southern California, Los Angeles, CA, USA. 14. Department of Urology, OLV Ziekenhuis Aalst, Melle, Belgium. 15. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, QC, Canada. 16. Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: briganti.alberto@hsr.it.
Abstract
BACKGROUND: Long-term outcomes of patients treated with salvage lymph node dissection (sLND) for nodal recurrence of prostate cancer (PCa) remain unknown. OBJECTIVE: To investigate long-term oncological outcomes after sLND in a large multi-institutional series. DESIGN, SETTING, AND PARTICIPANTS: The study included 189 patients who experienced prostate-specific antigen (PSA) rise and nodal-only recurrence after radical prostatectomy (RP) and underwent sLND at 11 tertiary referral centers between 2002 and 2011. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga prostate-specific membrane antigen ligand. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome of the study was cancer-specific mortality (CSM). The secondary outcomes were overall mortality, clinical recurrence (CR), biochemical recurrence (BCR), and androgen deprivation therapy (ADT)-free survival after sLND. The probability of freedom from each outcome was calculated using Kaplan-Meier analyses. Cox regression analysis was used to predict the risk of prostate CSM after accounting for several parameters, including the use of additional treatments after sLND. RESULTS AND LIMITATIONS: At long term, 110 and 163 patients experienced CR and BCR, respectively, with CR-free and BCR-free survival at 10 yr of 31% and 11%, respectively. After sLND, a total of 145 patients received ADT, with a median time to ADT of 41 mo. At a median (interquartile range) follow-up for survivors of 87 (51, 104) mo, 48 patients died. Of them, 45 died from PCa. The probabilities of freedom from cancer-specific and all-cause death at 10 yr were 66% and 64%, respectively. Similar results were obtained in sensitivity analyses in patients with pelvic-only positive PET/CT scan, as well as after excluding men on ADT at PET/CT scan and patients with PSA level at sLND higher than the 75th percentile. At multivariable analyses, patients who had PSA response after sLND (hazard ratio [HR]: 0.45; p = 0.001), and those receiving ADT within 6 mo from sLND (HR: 0.51; p = 0.010) had lower risk of death from PCa. CONCLUSIONS: A third of men treated with sLND for PET-detected nodal recurrence of PCa died at long term, with PCa being the main cause of death. Salvage LND alone was associated with durable long-term outcomes in a minority of men who significantly benefited from additional treatments after surgery. Taken together, all these data argue against the use of metastasis-directed therapy alone for patients with node-only recurrent PCa. These men should instead be considered at high risk of systemic dissemination already at the time of sLND. PATIENT SUMMARY: We assessed long-term outcomes of patients treated with salvage lymph node dissection (sLND) for node-recurrent prostate cancer (PCa). In contrast with prior evidence, we found that the majority of these men recurred after sLND and eventually died from PCa. A significant survival benefit associated with the administration of androgen deprivation therapy after sLND suggests that sLND should be considered part of a multimodal approach rather than an exclusive treatment strategy.
BACKGROUND: Long-term outcomes of patients treated with salvage lymph node dissection (sLND) for nodal recurrence of prostate cancer (PCa) remain unknown. OBJECTIVE: To investigate long-term oncological outcomes after sLND in a large multi-institutional series. DESIGN, SETTING, AND PARTICIPANTS: The study included 189 patients who experienced prostate-specific antigen (PSA) rise and nodal-only recurrence after radical prostatectomy (RP) and underwent sLND at 11 tertiary referral centers between 2002 and 2011. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga prostate-specific membrane antigen ligand. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome of the study was cancer-specific mortality (CSM). The secondary outcomes were overall mortality, clinical recurrence (CR), biochemical recurrence (BCR), and androgen deprivation therapy (ADT)-free survival after sLND. The probability of freedom from each outcome was calculated using Kaplan-Meier analyses. Cox regression analysis was used to predict the risk of prostate CSM after accounting for several parameters, including the use of additional treatments after sLND. RESULTS AND LIMITATIONS: At long term, 110 and 163 patients experienced CR and BCR, respectively, with CR-free and BCR-free survival at 10 yr of 31% and 11%, respectively. After sLND, a total of 145 patients received ADT, with a median time to ADT of 41 mo. At a median (interquartile range) follow-up for survivors of 87 (51, 104) mo, 48 patients died. Of them, 45 died from PCa. The probabilities of freedom from cancer-specific and all-cause death at 10 yr were 66% and 64%, respectively. Similar results were obtained in sensitivity analyses in patients with pelvic-only positive PET/CT scan, as well as after excluding men on ADT at PET/CT scan and patients with PSA level at sLND higher than the 75th percentile. At multivariable analyses, patients who had PSA response after sLND (hazard ratio [HR]: 0.45; p = 0.001), and those receiving ADT within 6 mo from sLND (HR: 0.51; p = 0.010) had lower risk of death from PCa. CONCLUSIONS: A third of men treated with sLND for PET-detected nodal recurrence of PCa died at long term, with PCa being the main cause of death. Salvage LND alone was associated with durable long-term outcomes in a minority of men who significantly benefited from additional treatments after surgery. Taken together, all these data argue against the use of metastasis-directed therapy alone for patients with node-only recurrent PCa. These men should instead be considered at high risk of systemic dissemination already at the time of sLND. PATIENT SUMMARY: We assessed long-term outcomes of patients treated with salvage lymph node dissection (sLND) for node-recurrent prostate cancer (PCa). In contrast with prior evidence, we found that the majority of these men recurred after sLND and eventually died from PCa. A significant survival benefit associated with the administration of androgen deprivation therapy after sLND suggests that sLND should be considered part of a multimodal approach rather than an exclusive treatment strategy.
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