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CASE REPORT
Ahead of print publication  

Stereotactic ablative radiotherapy for the primary site in a patient with nonmetastatic castration-resistant prostate cancer


 Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan

Date of Submission17-Feb-2022
Date of Decision05-Apr-2022
Date of Acceptance06-Apr-2022
Date of Web Publication25-May-2022

Correspondence Address:
Atsuto Katano,
Department of Radiology, The University of Tokyo Hospital, Tokyo
Japan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrcr.jrcr_13_22

  Abstract 

There is accumulating evidence regarding the efficacy and feasibility of stereotactic ablative radiotherapy (SABR) for localized prostate cancer. We report a case of nonmetastatic castration-resistant prostate cancer (nmCRPC) that was treated with SABR applied to the prostate. A Japanese 83-year-old man was referred to our hospital for a consultation regarding treatment for castration-resistant prostate cancer with an elevated prostate-specific antigen (PSA) level of 13.5 ng/mL. Pelvic magnetic resonance imaging revealed locally advanced cancer with seminal vesicle invasion. Contrast-enhanced computed tomography and bone scintigraphy showed neither nodal nor distant metastases. Consequently, he was diagnosed with nmCRPC. While receiving leuprolide in our hospital, his serum PSA level continued to increase to 16.6 ng/mL. He agreed to undergo SABR, which consisted of 5 fractions, 8 Gy per fraction, delivered every other day excluding weekends, to a total dose of 40 Gy. Six months after initiating SABR, the PSA level decreased to 0.79 ng/mL. Our report suggests that SABR contributes to the suppression of disease progression in patients with nmCRPC. Further studies are needed to determine the clinical benefit of SABR as a local therapy for nmCRPC.

Keywords: Nonmetastatic castration-resistant prostate cancer, primary site, stereotactic ablative radiotherapy



How to cite this URL:
Katano A. Stereotactic ablative radiotherapy for the primary site in a patient with nonmetastatic castration-resistant prostate cancer. J Radiat Cancer Res [Epub ahead of print] [cited 2022 Dec 4]. Available from: https://www.journalrcr.org/preprintarticle.asp?id=346043


  Introduction Top


The incidence of prostate cancer worldwide is estimated to be approximately 1.4 million per year, which is 14.1% of all male cancers, second only to lung cancer (14.3%).[1] The main treatment modalities for prostate cancer are surveillance, surgery, radiotherapy, hormone therapy, and chemotherapy. Although radiotherapy for prostate cancer is a radical local treatment along with surgery, conventionally fractionated radiotherapy requires a treatment period of approximately 8–9 weeks. With the development of radiotherapy modalities such as intensity-modulated radiotherapy and image-guided radiotherapy, it has become possible to safely perform hypofractionated radiotherapy. Moderate hypofractionated radiotherapy, which requires a treatment period of approximately 4–6 weeks, has been reported to yield similar clinical outcomes with similar radiation-related adverse event rates compared to those of conventionally fractionated radiotherapy.[2]

Ultra-hypofractionated radiotherapy or stereotactic ablative radiotherapy (SABR) is an advanced radiotherapy modality that delivers a high radiation dose in a single session and must be performed under precise image guidance. SABR for localized prostate cancer is conducted in no more than five fractionations, and there is accumulating evidence regarding its efficacy and feasibility. Here, we report a clinical case of nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with SABR for the primary site.


  Case Report Top


A Japanese 83-year-old man was referred to our hospital for a consultation regarding treatment for castration-resistant prostate cancer (CRPC). Seven years before his current visit to our hospital, he had been diagnosed with prostate cancer classified as clinical stage cT4N0M0 with an elevated prostate-specific antigen (PSA) level of 181 ng/mL at another hospital. At that time, he was administered androgen deprivation therapy (ADT) combined with bicalutamide and leuprolide. The PSA level decreased to the lowest level of 0.92 ng/mL; however, the PSA level increased again. One year before his current visit to our hospital, he was diagnosed with CRPC with an elevated PSA level of 9.4 ng/mL during ADT. He then received enzalutamide followed by abiraterone; however, the PSA level continued to increase to 13.5 ng/mL, and he was then referred to our hospital.

Contrast-enhanced computed tomography showed no significant lymph node enlargement or distant metastasis. No bone metastases were shown on bone scintigraphy. Pelvic magnetic resonance imaging showed a reduction in the zonal anatomy of the prostate, which was replaced by low-signal lesions on T2-weighted images [Figure 1]. The right seminal vesicle also showed an abnormal signal, suggesting seminal vesicle invasion from the prostate. Consequently, he was diagnosed with nmCRPC and administered treatment containing leuprolide and flutamide. Soon after, he discontinued flutamide treatment because he experienced discomfort.
Figure 1: Pelvic magnetic resonance image showed that a reduction in the zonal anatomy of the prostate, which was replaced by low-signal lesions on T2-weighted images

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Four months after the initial consultation at our hospital, the PSA level continued to increase to 16.6 ng/mL, and he agreed to undergo SABR for the prostate. He received five fractions of radiotherapy, 8 Gy per fraction, delivered every other day, excluding weekends, to a total dose of 40 Gy. The clinical target volume (CTV) was delineated as the entire prostate gland and seminal vesicle. The planning target volume (PTV) expanded the CTV with a 5 mm expansion in all directions, except 3 mm in the posterior direction. Radiotherapy planning was optimized to ensure that at least 95% of the PTV received the prescribed dose [Figure 2]. He experienced grade 1 urinary frequency as an acute adverse event, graded according to the Common Terminology Criteria for Adverse Events version 5.0. The PSA level decreased after the completion of radiotherapy and remained low even 1 year after SABR [Figure 3]. Neither late gastrointestinal nor genitourinary adverse events were experienced by him.
Figure 2: Dose distribution of the stereotactic ablative radiotherapy dose for prostate cancer. The isodose colors in centigray (cGy) are presented in the upper left corner

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Figure 3: Time course of the serum prostate-specific antigen (PSA) level. The serum level of PSA was 16.6 ng/mL before stereotactic ablative radiotherapy. Six months after initiating radiotherapy, the PSA level decreased to 0.79 ng/mL

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  Discussion Top


There are two patterns of nmCRPC: first, the disease progresses after hormone therapy for PSA elevation recurrence after radical prostatectomy or radiotherapy, and second, the disease progresses after hormone therapy without radical therapy, as in our case.[3] Recently, clinical evidence of antiandrogen therapy for patients with nmCRPC has accumulated.

A phase III trial, called the SPARTAN trial, revealed that ADT plus apalutamide significantly improves metastasis-free survival compared with that associated with ADT plus placebo (median: 40.5 vs. 16.2 months) in patients with nmCRPC (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.23–0.35, P < 0.001).[4] Another phase III trial, called the ARAMIS trial, evaluated the safety and efficacy of darolutamide in patients with nmCRPC. This trial showed that darolutamide plus ADT is associated with a significantly lower risk of death than that associated with ADT plus placebo (HR: 0.69, 95% CI: 0.53–0.88, P = 0.003).[5] The PROSPER trial, another phase III trial, compared ADT plus enzalutamide with ADT plus placebo in patients with nmCRPC. The metastasis-free survival was significantly longer in the enzalutamide group than that in the placebo group (median: 36.6 vs. 14.7 months) (HR: 0.29, 95% CI: 0.24–0.35, P < 0.001).[6]

Diagnostic imaging is becoming increasingly important to confirm the absence of distant metastases to identify nmCRPC. Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) has been attracting attention as a new diagnostic method. PSMA is a membrane protein expressed on the cell membrane, and prostate cancer cells express high levels of PSMA. Hofman et al. reported that gallium-68 PSMA-11 PET-CT yields a higher sensitivity and specificity than those of conventional methods for imaging pelvic nodal or distant metastases in prostate cancer.[7]

We described a clinical case of nmCRPC that was treated with SABR. King et al. revealed that SABR is associated with favorable outcomes with respect to the 5-year biochemical relapse-free survival rate compared to those of other treatment modalities in patients with low-to intermediate-risk prostate cancer.[8] Kishan et al. reported that SABR for low-and intermediate-risk prostate cancer sufficiently suppresses biochemical failure without increasing severe genitourinary or gastrointestinal toxic late adverse events.[9] Moreover, dose-escalated SABR achieved a favorable outcome in high-risk prostate cancer cases.[10] Our report suggests that SABR may contribute to the suppression of disease progression in patients with nmCRPC. Further studies are needed to determine the clinical benefit of SABR as a local therapy for nmCRPC.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.  Back to cited text no. 1
    
2.
Incrocci L, Wortel RC, Alemayehu WG, Aluwini S, Schimmel E, Krol S, et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): Final efficacy results from a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 2016;17:1061-9.  Back to cited text no. 2
    
3.
Mateo J, Fizazi K, Gillessen S, Heidenreich A, Perez-Lopez R, Oyen WJG, et al. Managing nonmetastatic castration-resistant prostate cancer. Eur Urol 2019;75:285-93.  Back to cited text no. 3
    
4.
Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378:1408-18.  Back to cited text no. 4
    
5.
Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med 2020;383:1040-9.  Back to cited text no. 5
    
6.
Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, et al. Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2020;382:2197-206.  Back to cited text no. 6
    
7.
Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): A prospective, randomised, multicentre study. Lancet 2020;395:1208-16.  Back to cited text no. 7
    
8.
King CR, Freeman D, Kaplan I, Fuller D, Bolzicco G, Collins S, et al. Stereotactic body radiotherapy for localized prostate cancer: Pooled analysis from a multi-institutional consortium of prospective phase II trials. Radiother Oncol 2013;109:217-21.  Back to cited text no. 8
    
9.
Kishan AU, Dang A, Katz AJ, Mantz CA, Collins SP, Aghdam N, et al. Long-term outcomes of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. JAMA Netw Open 2019;2:e188006.  Back to cited text no. 9
    
10.
Hannan R, Salamekh S, Desai NB, Garant A, Folkert MR, Costa DN, et al. SAbR for high-risk prostate cancer – A prospective multilevel MRI-based dose escalation trial. Int J Radiat Oncol Biol Phys. 2021 Nov 11;S0360-3016(21)03047-9. [doi: 10.1016/j.ijrobp.2021.10.137].  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

 
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