Prostate Cancer with Isolated Bony Metastasis: Sternal Struggle Mark T

International Journal of Radiation Oncology biology physics

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Prostate Cancer With Isolated Bony Metastasis: Sternal Struggle Mark T. Corkum, MD, MSc

Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada

A 70-year-old man presented with lower urinary tract symptoms including nocturia and frequency. Digital rectal examination revealed a 3þ prostate with bilateral increased ﬁrmness with no nodules, concerning for malignancy. The prostate-speciﬁc antigen (PSA) was elevated at 80 mg/L. There was no bony pain and no constitutional symptoms. Transrectal ultrasound-guided prostate biopsy was performed. Examination of the biopsy specimen revealed Gleason 9 (5 þ 4) prostate adenocarcinoma involving 12 of 12 cores and 90% of prostatic tissue with evidence of perineural and periprostatic fat invasion.

Fig. 1. Total body bone scan demonstrating increased tracer uptake in the sternum. C6 vertebral body tracer uptake was found to be due to osteophytosis, and the remainder of tracer uptake was degenerative.

Conﬂict of interest: none.

AcknowledgmentdThe author thanks Dr Glenn Bauman, Dr David Palma, and Dr Tracy Sexton of the London Regional Cancer Program for reviewing this article.

Int J Radiation Oncol Biol Phys, Vol. 98, No. 3, pp. 492-493, 2017 0360-3016/$ - see front matter Ó 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2017.03.035 Volume 98 Number 3 2017 Gray Zone 493

Fig. 2. Selected sagittal (a) and coronal (b) computed tomography slices demonstrating the sclerotic bone metastasis in the sternum, measuring 2.8 1.8 in the coronal plane.

Bone scan demonstrated a solitary bone metastasis in the sternum. Magnetic resonance imaging of the spine was ordered to characterize C6 vertebral body tracer uptake, determined to be osteophytosis. Other ﬁndings were degenerative. Computed tomography (CT) of the abdomen and pelvis did not demonstrate lymphadenopathy. The patient was given hormone therapy with a GnRH agonist. After discussion with medical oncology, the patient was given docetaxel chemotherapy for 6 cycles, and no adverse events occurred. His PSA became undetectable (<0.1 mg/L) after chemotherapy, and ongoing hormone therapy was planned. His urinary symptoms improved with medical management. A posttreatment bone scan demonstrated decreased but persistent tracer uptake in the sternum (Fig. 1). Repeated CT of the chest, abdomen, and pelvis demonstrated a 2.8 1.8 cm sclerotic metastasis in the sternum without other metastases (Fig. 2). He had mild sternal pain with coughing. His medical history was signiﬁcant for hypertension, dyslipidemia, and type II diabetes without evidence of end-organ damage. A referral to radiation oncology was made. His performance status was excellent, and he was willing to consider all treatment options.

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GRAY ZONE EXPERT OPINIONS

Treat All Known Disease Conflict of interest: none. This patient (1) presents with oligometastatic, Gleason 5 þ 4 adenocarcinoma, with a presenting prostate-specific References antigen level of 80 mg/L. On the basis of the biopsy extension into periprostatic fat, he has T3a disease. He has 1. Corkum MT. Prostate cancer with isolated bony metastasis: Sternal been treated initially with androgen deprivation therapy and struggle. Int J Radiat Oncol Biol Phys 2017;98:492-493. docetaxel. On the basis of the STAMPEDE data, he can 2. James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic expect a median response duration of 3 years and survival acid, or both to first-line long-term hormone therapy in prostate cancer of 6 years (2). He may, however, not achieve this having a (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 2016;387:1163-1177. high-grade tumor, which predicts for a shorter response to 3. Bhattacharya IS, Hoskin PJ. Stereotactic body radiotherapy for spinal androgen deprivation therapy. He is 70 years old with and bone metastases. Clin Oncol (R Coll Radiol) 2015;27:298-306. limited comorbidities, which are unlikely to compromise 4. James ND, Spears MR, Clarke NW, et al. Failure-free survival and his survival over the next 10 years. radiotherapy in patients with newly diagnosed nonmetastatic prostate The patient’s prostate-specific antigen level is currently cancer: Data from patients in the control arm of the STAMPEDE trial. JAMA Oncol 2016;2:348-357. undetectable, which will reflect his response to androgen 5. Hoskin PJ, Rojas AM, Bownes PJ, et al. Randomised trial of external ablation, and his performance status is excellent. The only beam radiotherapy alone or combined with high-dose-rate brachytherapy abnormality is persistent uptake on isotope bone scan in the boost for localised prostate cancer. Radiother Oncol 2012;103:217-222. sternum, which may reflect osteoblastic healing rather than 6. Spratt DE, Zumsteg ZS, Ghadjar P, et al. Comparison of high-dose active tumor. (86.4 Gy) IMRT vs combined brachytherapy plus IMRT for intermediate-risk prostate cancer. BJU Int 2014;114:360-367. In this setting, I would offer the patient radical ablative radiation therapy. Local treatment to the sternum with a stereotactic or electron technique to minimize dose to the heart http://dx.doi.org/10.1016/j.ijrobp.2016.12.006 and lungs delivering 21 Gy in 3 fractions will achieve local control in >90% of cases (3). I would also treat the pelvis with high-dose radiation therapy. The patient’s risk of occult sem- Prostate-Specific Membrane Antigen inal vesicle and lymph node metastases is high, and improved PET Before Aggressive Local Therapy failure-free survival has been demonstrated from nodal radiation therapy in patients with Nþ disease (4).Inhigh-risk to the Sternum disease, the combination of external beam radiation therapy and brachytherapy has a better outcome than external beam In the absence of major competing medical comorbidities, du- radiation therapy alone (5, 6). I would therefore offer radiation rable local control will be a significant issue during the projected therapy to the prostate, seminal vesicles, and regional lymph lifetime of this man (1). In men who present with such high- nodes with intensity modulated radiation therapy delivering volume and high-grade (group 5) prostate disease concur- 46 Gy in 23 fractions, followed by high-dose-rate brachy- rently with lower urinary tract symptoms, insufficient control therapy implanting the prostate, periprostatic tissues, and long term is often observed with medical management alone. seminal vesicles delivering a boost of 15 Gy. Therefore, after discussion at a multidisciplinary tumor board, I would recommend local treatment of the prostate Peter J. Hoskin alone with radiation therapy. A hypofractionated schedule of Mount Vernon Cancer Centre 55 Gy in 20 fractions to the prostate is likely to provide Northwood, UK adequate palliation and is commonplace in Australia and

Int J Radiation Oncol Biol Phys, Vol. 98, No. 3, pp. 494-496, 2017 0360-3016/$ - see front matter Ó 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2017.01.029 Volume 98 Number 3 2017 Gray Zone Expert Opinions 495 the United Kingdom. As the sternal disease is asymptomatic, bony and nodal targets is associated with high local control however, I would first arrange functional imaging and minimal toxicity (1). The use of SBRT to defer treatment with positron emission tomography (PET) before entertaining with androgen deprivation therapy (ADT) (median 28 months a more aggressive treatment paradigm. PETwith 68Ga-labeled in reference [1]) suggests a significant quality of life benefit. prostate-specific membrane antigen (PSMA) is a highly Retrospective population-based studies suggest im- promising imaging technique with higher sensitivity for provements in disease-specific and overall survival with metastatic disease than 18F-fluoromethylcholine PET (2). This definitive prostatic management (surgery or radiation would be the ideal choice for detection of additional disease therapy) in metastatic disease; however, there is likely that is occult on conventional radiographic modalities. significant selection bias, with <5% of the presenting If the sternum truly had an isolated “oligometastasis” on population treated (2). Randomized data are lacking. PSMA-PET, then one could consider treating this with Prostate SBRT is a convenient treatment approach for stereotactic body radiation therapy. Given the high-grade patients with metastatic disease but is unproven for high- disease, worrisome PSA level elevation, and synchronous risk disease, and concerns regarding potential gastrointes- presentation with metastases, it is highly unlikely that this tinal toxicity with inclusion of pelvic lymph nodes were patient will have long-term disease control, and he must be noted in the only reported prospective series. fully informed prior to embarking on this treatment Our patient (3) has already been exposed to systemic approach. Our institution has observed through a prospec- chemotherapy and ongoing ADT, thus the ability to defer these tive clinical trial that a single fraction of 20 Gy is associ- treatments (and toxicities) has passed. In the absence of data ated with local control rates >90% and minimal toxicity in showing a convincing benefit to treating the primary cancer in patients with bony prostate oligometastases (3). upfront oligometastatic disease (such as the ongoing study NCT01751438), we are concerned about potential toxicity in Shankar Siva, PhD, MBBS, FRANZCR treating his significant primary disease. With his ongoing ADT Department of Radiation Oncology Peter MacCallum Cancer Centre (and expected excellent palliative benefit to conventional ra- Melbourne, Victoria, Australia diation), we also have no benchmark to assess the efficacy of Sir Peter MacCallum Department of Oncology SBRT in this patient once delivered. Had he presented with University of Melbourne delayed and isolated sternal metastasis after primary man- Melbourne, Victoria, Australia agement, we would have considered SBRT (30 Gy in 3 fractions). At present, we recommend ADT and conventional Conflict of interest: none. palliative radiation therapy if symptoms warrant. References Kevin L. Stephans, MD Rupesh Kotecha, MD 1. Corkum MT. Prostate cancer with isolated bony metastasis: Sternal Department of Radiation Oncology, Taussig Cancer Center struggle. Int J Radiat Oncol Biol Phys 2017;98:492-493. Cleveland Clinic, Cleveland, Ohio 2. Afshar-Oromieh A, Zechmann CM, Malcher A, et al. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline- Conflict of interest: none. based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2014;41:11-20. 3. Siva S, Hofman MS, Kron T, et al. Sodium fluoride (NaF) PET/CT References response assessment in a prospective pilot study of oligometastases from prostate cancer treated with stereotactic ablative radiosurgery 1. Ost P, Jereczek-Fossa BA, As NV, et al. Progression-free survival (POPSTAR). Asia Pac J Clin Oncol 2016;12:42. following stereotactic body radiotherapy for oligometastatic prostate cancer treatment-naive recurrence: A multi-institutional analysis. Eur http://dx.doi.org/10.1016/j.ijrobp.2017.01.029 Urol 2016;69:9-12. 2. Rusthoven CG, Jones BL, Flaig TW, et al. Improved survival with prostate radiation in addition to androgen deprivation therapy for men with newly diagnosed metastatic prostate cancer. JClinOncol2016;34:2835-2842. Intriguing, but Not the Right Setting 3. Corkum MT. Prostate cancer with isolated bony metastasis: Sternal struggle. Int J Radiat Oncol Biol Phys 2017;98:492-493. Stereotactic body radiation therapy (SBRT) offers an http://dx.doi.org/10.1016/j.ijrobp.2017.01.215 intriguing treatment option for men with oligometastatic prostate cancer. Several series document that treatment of 496 Gray Zone Expert Opinions International Journal of Radiation Oncology Biology Physics

Sternum First, Perhaps Pelvis Later CA200551). While data are retrospective and limited, single-fraction SBRT with a minimum dose of 18 to 20 Gy To consider the questions regarding further management is associated with high local control rates and favorable and consideration of radiation therapy, additional patient logistics. The discussion with the patient should acknowl- history and evaluation may be appropriate including the edge there is no high-level evidence of the superiority of following: SBRT over conventional external beam radiation therapy for pain control. To avoid unnecessary lung irradiation, one History of urinary obstructive symptoms before and after may consider delivery with proton irradiation if available systemic therapy with the International Prostate Symp- and, if feasible, affordable and within the context of a tom Score. prospective clinical trial or registry study. Measurement of the serum testosterone level to document If the patient (3) has demonstrated worsening urinary effective androgen deprivation and the castrate testos- obstructive symptoms, there are retrospective data sup- terone level. porting the use of high-dose prostate radiation therapy to Measurement of chromogranin A levels. If incomplete provide local control and prevent the development of uri- response to androgen deprivation is observed, suspicion nary retention or worsening obstructive symptoms. While of the development of neuroendocrine dedifferentiation radiotherapeutic management of patients with oligometa- should be addressed. Chromogranin A levels may iden- static disease is an active area of investigation (2), delivery tify such dedifferentiation. of prophylactic radiation therapy to the primary and adja- Advanced positron emission tomography (PET) imaging cent nodal sites outside the scope of a clinical trial would as available that may include 11Cor18F choline, 68Ga not be routinely recommended for such a patient at this prostate specific membrane antigen, 18F fluciclovine, or point in time. 11C acetate to determine if there is evidence of active nodal, visceral disease, or other sites of bone Brian J. Davis, MD, PhD metastases. If other sites appear involved, then biopsy, if Sean S. Park, MD, PhD feasible, should be considered. In the context of an un- Department of Radiation Oncology detectable prostate-specific antigen level, active disease Mayo Clinic on PET and biopsy may confirm neuroendocrine dedif- Rochester, Minnesota ferentiation or a second malignancy. If further evidence of neuroendocrine dedifferentiation of prostate cancer is Conflict of interest: none. identified, then fluorodeoxyglucose PET may also be useful. References If all other workup findings are unremarkable and the clinical picture of an isolated symptomatic bone metastasis 1. Lutz S, Balboni T, Jones J, et al. Palliative radiation therapy for bone is confirmed, then delivering palliative radiation therapy metastases: Update of an ASTRO Evidence-Based Guideline. Pract consistent with updated American Society for Radiation Radiat Oncol 2017;7:4-12. Oncology guidelines would be recommended (1). At our 2. Corbin KS, Hellman S, Weichselbaum RR. Extracranial oligometa- institution, the preferred method would be to deliver ste- stases: A subset of metastases curable with stereotactic radiotherapy. reotactic body radiation therapy (SBRT) to the sternal J Clin Oncol 2013;31:1384-1390. 3. Corkum MT. Prostate cancer with isolated bony metastasis: Sternal lesion with the patient being entered into a registry study struggle. Int J Radiat Oncol Biol Phys 2017;98:492-493. or an ongoing phase 2 prospective trial for 11C choline PETepositive lesions (National Cancer Institute http://dx.doi.org/10.1016/j.ijrobp.2017.04.020

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