Trends in Management of Oligometastatic Hormone-Sensitive Prostate Cancer
Purpose of Review
Systemic therapy for patients with hormone-sensitive oligometastatic prostate cancer is non-curative and associated with toxicities. Meanwhile, this population presents unique clinical opportunities to improve outcomes, including the demonstrated benefits of radiotherapy to the primary tumor or oligometastatic sites.
Recently published randomized studies have demonstrated benefits with the addition of radiotherapy to the primary disease or metastatic lesions in patients with synchronous or metachronous disease. The introduction of novel PET imaging has improved the sensitivity and specificity for detecting metastatic disease and provides an opportunity to better select patients who will benefit from local therapy.
The data presented in this review supports revisiting practice guidelines for patients with hormone-sensitive metastatic prostate cancer, particularly in relation to the role of radiotherapy to the primary tumor and sites of oligometastatic disease. Future trials will aim to further establish the role of metastasis-directed therapies in metachronous, synchronous, and castrate-resistant disease.
KeywordsOligometastases Metastasis directed therapy SBRT Prostate cancer
Alison C. Tree and Nicholas J. van As “This paper represents independent research supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.”
Compliance with Ethical Standards
Conflict of Interest
Gargi Kothari declares that he has no conflict of interest.
Piet Ost declares that he has no conflict of interest.
Patrick Cheung is supported by an investigator-initiated industry research grant (to fund a current Phase I/II trial in hormone-sensitive oligometastatic prostate cancer) from AbbVie.
Pierre Blanchard has received research support through grants from Astellas and Amgen.
Alison C. Tree has received research support through grants from MSD and Elekta, and has received compensation from Bayer, Astellas, Janssen, and Ferring Pharmaceuticals for service as a consultant.
Nicholas J. van As has received both research grants as well as compensation for service as a consultant from Accuray.
Simon S. Lo served as an expert group member for the Elekta ICON and also received partial research support from Elekta for the International Oligometastasis Consortium (ended in July 2016).
Drew Moghanaki has received reimbursement for travel expenses and compensation for service as a consultant from Varian Medical Systems.
Andrew Loblaw has received research support through grants from AbbVie, Astellas, Janssen, Sanofi, AstraZeneca, and TerSera Therapeutics; has received compensation from AbbVie, Bayer, Astellas, Janssen, Sanofi, AstraZeneca, and TerSera Therapeutics for service as a consultant; has received non-financial support from Astellas, Janssen, AstraZeneca, and TerSera Therapeutics; and has a patent issued on a prostate immobilization device.
Shankar Siva has received research support through grants from Varian Medical Systems and MSD; has received compensation from AstraZeneca, Bristol-Myers Squibb, Astellas, Roche, and Janssen for service on advisory boards; and has received reimbursement for travel expenses from AstraZeneca Bristol-Myers Squibb, and Astellas.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 3.Lecouvet FE, Oprea-Lager DE, Liu Y, Ost P, Bidaut L, Collette L, et al. Use of modern imaging methods to facilitate trials of metastasis-directed therapy for oligometastatic disease in prostate cancer: a consensus recommendation from the EORTC imaging group. Lancet Oncol. 2018;19(10):e534–e45. https://doi.org/10.1016/s1470-2045(18)30571-0.CrossRefPubMedGoogle Scholar
- 4.Palma DA, Olson RA, Harrow S, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic ablative radiation therapy for the comprehensive treatment of oligometastatic tumors (SABR-COMET): results of a randomized trial. Int J Radiat Oncol Biol Phys. 2018;102(3):S3–4. https://doi.org/10.1016/j.ijrobp.2018.06.105.CrossRefGoogle Scholar
- 7.• Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, Multicenter Phase II. Trial J Clin Oncol. 2018;36(5):446–53. https://doi.org/10.1200/JCO.2017.75.4853 First randomized Phase II trial of observation versus metastasis directed therapy in patients with hormone sensitive oligometastatic prostate cancer which showed improved ADT-free survival in metastasis directed therapy arm (21 vs 13 months, HR 0.60, 80% CI 0.40–0.90, p = 0.11). CrossRefPubMedGoogle Scholar
- 10.James ND, Spears MR, Clarke NW, Dearnaley DP, Mason MD, Parker CC, et al. Failure-free survival and radiotherapy in patients with newly diagnosed nonmetastatic prostate cancer: data from patients in the control arm of the STAMPEDE trial. JAMA Oncol. 2016;2(3):348–57. https://doi.org/10.1001/jamaoncol.2015.4350.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Rusthoven CG, Carlson JA, Waxweiler TV, Raben D, Dewitt PE, Crawford ED, et al. The impact of definitive local therapy for lymph node-positive prostate cancer: a population-based study. Int J Radiat Oncol Biol Phys. 2014;88(5):1064–73. https://doi.org/10.1016/j.ijrobp.2014.01.008.CrossRefPubMedGoogle Scholar
- 13.Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018;36(11):1080–7. https://doi.org/10.1200/JCO.2017.75.3657.CrossRefPubMedGoogle Scholar
- 14.James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163–77. https://doi.org/10.1016/S0140-6736(15)01037-5.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Nair B, Wilt T, MacDonald R, Rutks I. Early versus deferred androgen suppression in the treatment of advanced prostatic cancer. Cochrane Database Syst Rev. 2002;(1):CD003506. https://doi.org/10.1002/14651858.CD003506.
- 19.Mottet N, van den Bergh RCN, Briers E, Bourke L, Cornford P, De Santis M, et al. EAU - ESTRO - ESUR - SIOG Guidelines on Prostate Cancer 2018. European Association of Urology Guidelines. 2018 Edition. Arnhem: European Association of Urology Guidelines Office; 2018.Google Scholar
- 20.Duchesne GM, Woo HH, Bassett JK, Bowe SJ, D'Este C, Frydenberg M, et al. Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. Lancet Oncol. 2016;17(6):727–37. https://doi.org/10.1016/S1470-2045(16)00107-8.CrossRefPubMedGoogle Scholar
- 28.• Boeve LMS, Hulshof M, Vis AN, Zwinderman AH, Twisk JWR, Witjes WPJ, et al. Effect on survival of androgen deprivation therapy alone compared to androgen deprivation therapy combined with concurrent radiation therapy to the prostate in patients with primary bone metastatic prostate cancer in a prospective randomised clinical trial: data from the HORRAD trial. Eur Urol. 2018. https://doi.org/10.1016/j.eururo.2018.09.008 First randomized Phase III trial of ADT +/− prostate radiotherapy in patients with synchronous oligometastatic prostate cancer, which showed an overall survival benefit to the addition of radiotherapy, although this was not statistically significant. An unplanned subgroup analysis showed a greater effect size for survival in patients with low volume metastatic disease (not statistically significant).
- 29.• Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392:2353–66. https://doi.org/10.1016/S0140-6736(18)32486-3 Randomized Phase III trial of ADT +/- prostate radiotherapy which showed a statistically significant overall survival benefit in patients with low volume metastatic disease.CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Satkunasivam R, Kim AE, Desai M, Nguyen MM, Quinn DI, Ballas L, et al. Radical prostatectomy or external beam radiation therapy vs no local therapy for survival benefit in metastatic prostate cancer: a SEER-Medicare analysis. J Urol. 2015;194(2):378–85. https://doi.org/10.1016/j.juro.2015.02.084.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Loppenberg B, Dalela D, Karabon P, Sood A, Sammon JD, Meyer CP, et al. The impact of local treatment on overall survival in patients with metastatic prostate cancer on diagnosis: a National Cancer Data Base Analysis. Eur Urol. 2017;72(1):14–9. https://doi.org/10.1016/j.eururo.2016.04.031.CrossRefPubMedGoogle Scholar
- 35.Pompe RS, Tilki D, Preisser F, Leyh-Bannurah SR, Bandini M, Marchioni M, et al. Survival benefit of local versus no local treatment for metastatic prostate cancer-impact of baseline PSA and metastatic substages. Prostate. 2018;78(10):753–7. https://doi.org/10.1002/pros.23519.CrossRefPubMedGoogle Scholar
- 36.Fossati N, Trinh QD, Sammon J, Sood A, Larcher A, Sun M, et al. Identifying optimal candidates for local treatment of the primary tumor among patients diagnosed with metastatic prostate cancer: a SEER-based study. Eur Urol. 2015;67(1):3–6. https://doi.org/10.1016/j.eururo.2014.08.056.CrossRefPubMedGoogle Scholar
- 40.Porres D, Pfister D, Thissen A, Kuru TH, Zugor V, Buettner R, et al. The role of salvage extended lymph node dissection in patients with rising PSA and PET/CT scan detected nodal recurrence of prostate cancer. Prostate Cancer Prostatic Dis. 2017;20(1):85–92. https://doi.org/10.1038/pcan.2016.54.CrossRefPubMedGoogle Scholar
- 42.Oderda M, Joniau S, Melloni G, Falcone M, Munegato S, Tosco L, et al. Outcomes of salvage lymph node dissection for prostate cancer with clinical nodal relapse: results of a multicentric, retrospective study. EMJ. 2016;1(2):108–15.Google Scholar
- 45.Suardi N, Gandaglia G, Gallina A, Di Trapani E, Scattoni V, Vizziello D, 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(2):299–309. https://doi.org/10.1016/j.eururo.2014.02.011.CrossRefPubMedGoogle Scholar
- 47.Rigatti P, Suardi N, Briganti A, Da Pozzo LF, Tutolo M, Villa L, et al. Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography. Eur Urol. 2011;60(5):935–43. https://doi.org/10.1016/j.eururo.2011.07.060.CrossRefPubMedGoogle Scholar
- 48.Fossati N, Suardi N, Gandaglia G, Bravi CA, Soligo M, Karnes RJ, et al. Identifying the optimal candidate for salvage lymph node dissection for nodal recurrence of prostate cancer: results from a large, multi-institutional analysis. Eur Urol. 2019;75(1):176–83. https://doi.org/10.1016/j.eururo.2018.09.009.CrossRefPubMedGoogle Scholar
- 51.• Siva S, Bressel M, Murphy DG, Shaw M, Chander S, Violet J, et al. Stereotactic abative body radiotherapy (SABR) for oligometastatic prostate cancer: a prospective clinical trial. Eur Urol. 2018;74(4):455–62. https://doi.org/10.1016/j.eururo.2018.06.004 Single arm prospective trial of single fraction SBRT in patients with hormone sensitive oligometastatic prostate cancer, which showed 2-year local PFS of 93%, 2-year distant PFS of 39% and 2-year ADT-free survival of 48%. CrossRefPubMedGoogle Scholar
- 52.• Tran P, Radwan N, Phillips R, Ross A, Rowe S, Gorin M, et al. OC-0505: interim results of a randomized trial of observation versus SABR for oligometastatic prostate cancer. Radiother Oncol. 2018;127:S261. https://doi.org/10.1016/s0167-8140(18)30815-6 Interim results of phase II randomized trial of observation versus SBRT for hormone sensitive oligometastatic prostate cancer showed progression at 6 months of 67% in observation versus 33% in SBRT arm. CrossRefGoogle Scholar
- 54.Ost P, Bossi A, Decaestecker K, De Meerleer G, Giannarini G, Karnes RJ, et al. Metastasis-directed therapy of regional and distant recurrences after curative treatment of prostate cancer: a systematic review of the literature. Eur Urol. 2015;67(5):852–63. https://doi.org/10.1016/j.eururo.2014.09.004.CrossRefPubMedGoogle Scholar
- 55.Kneebone A, Hruby G, Ainsworth H, Byrne K, Brown C, Guo L, et al. Stereotactic body radiotherapy for oligometastatic prostate cancer detected via prostate-specific membrane antigen positron emission tomography. Eur Urol Oncol. 2018;1(6):531–7. https://doi.org/10.1016/j.euo.2018.04.017.CrossRefGoogle Scholar
- 56.Moghanaki D, Turkbey B, Vapiwala N, Ehdaie B, Frank SJ, McLaughlin PW, et al. Advances in prostate cancer magnetic resonance imaging and positron emission tomography-computed tomography for staging and radiotherapy treatment planning. Semin Radiat Oncol. 2017;27(1):21–33. https://doi.org/10.1016/j.semradonc.2016.08.008.CrossRefPubMedGoogle Scholar
- 59.Evangelista L, Bertoldo F, Boccardo F, Conti G, Menchi I, Mungai F, et al. Diagnostic imaging to detect and evaluate response to therapy in bone metastases from prostate cancer: current modalities and new horizons. Eur J Nucl Med Mol Imaging. 2016;43(8):1546–62. https://doi.org/10.1007/s00259-016-3350-4.CrossRefPubMedGoogle Scholar
- 60.Fanti S, Minozzi S, Castellucci P, Balduzzi S, Herrmann K, Krause BJ, et al. PET/CT with (11)C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data. Eur J Nucl Med Mol Imaging. 2016;43(1):55–69. https://doi.org/10.1007/s00259-015-3202-7.CrossRefPubMedGoogle Scholar
- 63.Fendler WP, Calais J, Allen-Auerbach M, Bluemel C, Eberhardt N, Emmett L, et al. (68)Ga-PSMA-11 PET/CT interobserver agreement for prostate cancer assessments: an international multicenter prospective study. J Nucl Med. 2017;58(10):1617–23. https://doi.org/10.2967/jnumed.117.190827.CrossRefPubMedGoogle Scholar
- 64.Corfield J, Perera M, Bolton D, Lawrentschuk N. (68)Ga-prostate specific membrane antigen (PSMA) positron emission tomography (PET) for primary staging of high-risk prostate cancer: a systematic review. World J Urol. 2018;36(4):519–27. https://doi.org/10.1007/s00345-018-2182-1.CrossRefPubMedGoogle Scholar
- 65.Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, specificity, and predictors of positive 68Ga–prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;70(6):926–37.CrossRefGoogle Scholar
- 70.Lohaus F, Zophel K, Lock S, Wirth M, Kotzerke J, Krause M, et al. Can local ablative radiotherapy revert castration-resistant prostate cancer to an earlier stage of disease? Eur Urol. 2018. https://doi.org/10.1016/j.eururo.2018.11.050.