Nina-Sophie Schmidt-Hegemann1, Christian Stief2, Tak-Hyun Kim3, Chukwuka Eze4, Simon Kirste3, Iosif Strouthos3, Minglun Li4, Wolfgang Schultze-Seemann5, Harun Ilhan6, Wolfgang Peter Fendler7, Peter Bartenstein6, Anca-Ligia Grosu3, Ute Ganswindt8, Claus Belka4, Philipp T Meyer9, Constantinos Zamboglou3. 1. Ludwig-Maximilians-University (LMU), Germany. 2. Department of Urology, University Hospital, LMU Munich, Germany. 3. Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, Germany. 4. Department of Radiation Oncology, University Hospital, LMU Munich, Germany. 5. Department of Urology, Medical Center - University of Freiburg, Faculty of Medicine, Germany. 6. Department of Nuclear Medicine, University Hospital, LMU Munich, Germany. 7. Department of Nuclear Medicine, University Hospital Essen, Germany. 8. Department of Therapeutic Radiology and Oncology, Innsbruck Medical University, Austria. 9. Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, Germany.
Abstract
Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) detects prostate cancer recurrence at low PSA levels. Radiotherapy with dose escalation to the former prostate bed has been associated with improved biochemical recurrence-free survival (BRFS). Thus, we hypothesized that PSMA PET/CT-guided salvage radiotherapy leads to improved BRFS. Methods: A total of 204 consecutive patients were referred for salvage radiotherapy following radical prostatectomy. PSMA PET/CT scans were performed and patients with PSA persistence (109 patients) or evidence of distant metastases (5 patients) were excluded from this analysis. Thus, the following analysis is based on a total of 90 patients who underwent PSMA PET/CT prior to radiotherapy due to biochemical recurrence and received salvage radiotherapy. In case of PET-positive findings, antiandrogen therapy was commenced before initiation of radiotherapy. BRFS (PSA ≤ 0.2 ng/ml) was defined as the study endpoint. Results: PET-positive lesions were detected in 42/90 (47%) patients: 24/42 (27%) fossa recurrence only, 12/42 (13%) pelvic lymph nodes only and 6/42 (7%) fossa and pelvic lymph node recurrence. Median PSA before radiotherapy was 0.44 (0.11 - 6.24). Cumulatively, a total dose of 70.0 Gy (67.2 - 72 Gy) was delivered to local macroscopic tumor, 66 Gy (59.4 - 70.2 Gy) to the prostatic fossa, 60.8 Gy (54 - 66 Gy) to PET-positive lymph nodes and 50.4 Gy (45 - 50.4 Gy) to the lymphatic pathways. After a median follow-up of 23 months, BRFS was 78%. Antiandrogen therapy was ongoing in 4 patients at last follow-up. No significant difference in BRFS between PET-positive (74%) vs. PET-negative patients (82%; p>0.05) was observed at last follow-up. Two patients had late genitourinary toxicity grade 3 and no patient had gastrointestinal toxicity ≥ 3 (NCI-CTCAE v4.03). Conclusion: PSMA PET/CT-guided salvage radiotherapy is an effective and safe local treatment option. No difference in BRFS between PET-positive and PET-negative patients was observed, indicating effective targeting of PET-positive lesions. PSMA PET/CT when readily available should be offered to patients with PSA recurrence for treatment individualization.
Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) detects prostate cancer recurrence at low PSA levels. Radiotherapy with dose escalation to the former prostate bed has been associated with improved biochemical recurrence-free survival (BRFS). Thus, we hypothesized that PSMA PET/CT-guided salvage radiotherapy leads to improved BRFS. Methods: A total of 204 consecutive patients were referred for salvage radiotherapy following radical prostatectomy. PSMA PET/CT scans were performed and patients with PSA persistence (109 patients) or evidence of distant metastases (5 patients) were excluded from this analysis. Thus, the following analysis is based on a total of 90 patients who underwent PSMA PET/CT prior to radiotherapy due to biochemical recurrence and received salvage radiotherapy. In case of PET-positive findings, antiandrogen therapy was commenced before initiation of radiotherapy. BRFS (PSA ≤ 0.2 ng/ml) was defined as the study endpoint. Results: PET-positive lesions were detected in 42/90 (47%) patients: 24/42 (27%) fossa recurrence only, 12/42 (13%) pelvic lymph nodes only and 6/42 (7%) fossa and pelvic lymph node recurrence. Median PSA before radiotherapy was 0.44 (0.11 - 6.24). Cumulatively, a total dose of 70.0 Gy (67.2 - 72 Gy) was delivered to local macroscopic tumor, 66 Gy (59.4 - 70.2 Gy) to the prostatic fossa, 60.8 Gy (54 - 66 Gy) to PET-positive lymph nodes and 50.4 Gy (45 - 50.4 Gy) to the lymphatic pathways. After a median follow-up of 23 months, BRFS was 78%. Antiandrogen therapy was ongoing in 4 patients at last follow-up. No significant difference in BRFS between PET-positive (74%) vs. PET-negative patients (82%; p>0.05) was observed at last follow-up. Two patients had late genitourinary toxicity grade 3 and no patient had gastrointestinal toxicity ≥ 3 (NCI-CTCAE v4.03). Conclusion: PSMA PET/CT-guided salvage radiotherapy is an effective and safe local treatment option. No difference in BRFS between PET-positive and PET-negative patients was observed, indicating effective targeting of PET-positive lesions. PSMA PET/CT when readily available should be offered to patients with PSA recurrence for treatment individualization.
Authors: William U Shipley; Wendy Seiferheld; Himanshu R Lukka; Pierre P Major; Niall M Heney; David J Grignon; Oliver Sartor; Maltibehn P Patel; Jean-Paul Bahary; Anthony L Zietman; Thomas M Pisansky; Kenneth L Zeitzer; Colleen A F Lawton; Felix Y Feng; Richard D Lovett; Alexander G Balogh; Luis Souhami; Seth A Rosenthal; Kevin J Kerlin; James J Dignam; Stephanie L Pugh; Howard M Sandler Journal: N Engl J Med Date: 2017-02-02 Impact factor: 91.245
Authors: Wolfgang P Fendler; Matthias Eiber; Mohsen Beheshti; Jamshed Bomanji; Francesco Ceci; Steven Cho; Frederik Giesel; Uwe Haberkorn; Thomas A Hope; Klaus Kopka; Bernd J Krause; Felix M Mottaghy; Heiko Schöder; John Sunderland; Simon Wan; Hans-Jürgen Wester; Stefano Fanti; Ken Herrmann Journal: Eur J Nucl Med Mol Imaging Date: 2017-06 Impact factor: 9.236
Authors: Christoph Henkenberens; Christoph A VON Klot; Tobias L Ross; Frank M Bengel; Hans-Jürgen Wester; Hüper Katja; Hans Christiansen; Thorsten Derlin Journal: Anticancer Res Date: 2017-03 Impact factor: 2.480
Authors: Jeremie Calais; Johannes Czernin; Minsong Cao; Amar U Kishan; John V Hegde; Narek Shaverdian; Kiri Sandler; Fang-I Chu; Chris R King; Michael L Steinberg; Isabel Rauscher; Nina-Sophie Schmidt-Hegemann; Thorsten Poeppel; Philipp Hetkamp; Francesco Ceci; Ken Herrmann; Wolfgang P Fendler; Matthias Eiber; Nicholas G Nickols Journal: J Nucl Med Date: 2017-11-09 Impact factor: 10.057
Authors: Thomas A Hope; Rahul Aggarwal; Bryant Chee; Dora Tao; Kirsten L Greene; Matthew R Cooperberg; Felix Feng; Albert Chang; Charles J Ryan; Eric J Small; Peter R Carroll Journal: J Nucl Med Date: 2017-05-18 Impact factor: 10.057
Authors: Rahul D Tendulkar; Shree Agrawal; Tianming Gao; Jason A Efstathiou; Thomas M Pisansky; Jeff M Michalski; Bridget F Koontz; Daniel A Hamstra; Felix Y Feng; Stanley L Liauw; Matthew C Abramowitz; Alan Pollack; Mitchell S Anscher; Drew Moghanaki; Robert B Den; Kevin L Stephans; Anthony L Zietman; W Robert Lee; Michael W Kattan; Andrew J Stephenson Journal: J Clin Oncol Date: 2016-10-20 Impact factor: 44.544
Authors: Colleen A F Lawton; Jeff Michalski; Issam El-Naqa; Mark K Buyyounouski; W Robert Lee; Cynthia Menard; Elizabeth O'Meara; Seth A Rosenthal; Mark Ritter; Michael Seider Journal: Int J Radiat Oncol Biol Phys Date: 2008-10-22 Impact factor: 7.038
Authors: Christina Bluemel; Fraenze Linke; Ken Herrmann; Iva Simunovic; Matthias Eiber; Christian Kestler; Andreas K Buck; Andreas Schirbel; Thorsten A Bley; Hans-Juergen Wester; Daniel Vergho; Axel Becker Journal: EJNMMI Res Date: 2016-10-26 Impact factor: 3.138
Authors: Nina-Sophie Schmidt-Hegemann; Chukwuka Eze; Minglun Li; Paul Rogowski; Christian Schaefer; Christian Stief; Alexander Buchner; Constantinos Zamboglou; Wolfgang Peter Fendler; Ute Ganswindt; Clemens Cyran; Peter Bartenstein; Claus Belka; Harun Ilhan Journal: J Nucl Med Date: 2018-12-14 Impact factor: 10.057
Authors: Francesco Ceci; Lorenzo Bianchi; Marco Borghesi; Giulia Polverari; Andrea Farolfi; Alberto Briganti; Riccardo Schiavina; Eugenio Brunocilla; Paolo Castellucci; Stefano Fanti Journal: Eur J Nucl Med Mol Imaging Date: 2019-09-06 Impact factor: 9.236
Authors: Vincent Beck; Boris Schlenker; Annika Herlemann; Maria Apfelbeck; Alexander Buchner; Christian Gratzke; Christian G Stief; Stefan Tritschler Journal: World J Urol Date: 2018-09-17 Impact factor: 4.226
Authors: Felipe Couñago; Ana Aurora Díaz Gavela; Gemma Sancho; Irene Ortiz; Francisco José Marcos; Manuel Recio; Julio Fernández; Raquel Cano; Mar Jiménez; Israel J Thuissard; David Sanz-Rosa; Juan Castro Nováis; Eduardo Pardo; Yolanda Molina; Hugo Pérez García; Elia Del Cerro Journal: Rep Pract Oncol Radiother Date: 2019-08-08
Authors: Elisa Perry; Arpit Talwar; Kim Taubman; Michael Ng; Lih-Ming Wong; Russell Booth; Tom R Sutherland Journal: Eur J Nucl Med Mol Imaging Date: 2021-01-05 Impact factor: 9.236
Authors: M Unterrainer; C Eze; H Ilhan; S Marschner; O Roengvoraphoj; N S Schmidt-Hegemann; F Walter; W G Kunz; P Munck Af Rosenschöld; R Jeraj; N L Albert; A L Grosu; M Niyazi; P Bartenstein; C Belka Journal: Radiat Oncol Date: 2020-04-21 Impact factor: 3.481
Authors: Marco M E Vogel; Stephanie G C Kroeze; Christoph Henkenberens; Nina-Sophie Schmidt-Hegemann; Simon Kirste; Jessica Becker; Irene A Burger; Thorsten Derlin; Peter Bartenstein; Michael Mix; Christian la Fougère; Matthias Eiber; Hans Christiansen; Claus Belka; Anca L Grosu; Arndt-Christian Müller; Matthias Guckenberger; Stephanie E Combs Journal: Eur J Nucl Med Mol Imaging Date: 2020-03-16 Impact factor: 9.236
Authors: Christoph Oehler; Michel Zimmermann; Lukas Adam; Juergen Curschmann; Marcin Sumila; Räto T Strebel; Richard Cathomas; Qiyu Li; Uwe Schneider; Daniel R Zwahlen Journal: BMC Urol Date: 2019-09-09 Impact factor: 2.264