Bounce effect or local recurrence after low-dose-rate brachytherapy of the prostate? When prostate-specific membrane antigen positron emission tomography–computed tomography is false positive: a case report

Abstract

Introduction

Low-dose-rate brachytherapy has been increasingly utilized as a minimally invasive treatment option in patients with low- and intermediate-risk prostate cancer. Following 1–2 years of treatment, a “bounce phenomenon” might occur in approximately 30% of patients undergoing low-dose-rate brachytherapy, characterized by a transient rise in prostate-specific antigen levels followed by a subsequent decrease. This phenomenon has been identified as a favorable prognostic factor. To date, only a few cases of a potential false-positive prostate-specific membrane antigen positron emission tomography–computed tomography related to the bounce phenomenon have been reported in literature. By presenting our clinical case, we aim to suggest refinements in the follow-up strategies and to assess the diagnostic value of prostate-specific membrane antigen positron emission tomography–computed tomography in managing cases with the bounce phenomenon.

Case presentation

A 66-year-old Caucasian (western European) male patient achieved a prostate-specific antigen nadir of 1.37 µg/l at 9 months after undergoing brachytherapy. At 21 months post-procedure, his prostate-specific antigen rose to 4.16 µg/l—following a period of stable and low prostate-specific antigen levels—prompting his general practitioner to refer him for prostate-specific membrane antigen positron emission tomography–computed tomography (298 MBq F-18-PSMA). Imaging revealed a prostate-specific membrane antigen-avid lesion within the prostate, suggesting a local recurrence, resulting in the offer of salvage therapy for the patient. However, a routine prostate-specific antigen screening before initiating salvage radiotherapy revealed a decrease to 3.75 µg/l with an additional reduction to 2.68 µg/l at 2 months later. The pattern of transient prostate-specific antigen elevation strongly suggested a bounce phenomenon rather than a recurrence, allowing any unnecessary treatment to be avoided. To date, prostate-specific antigen levels have been decreasing to as low as 0.48 µg/l, showing a satisfactory progress.

Conclusion

Our case illustrates a sporadically recognized false-positive prostate-specific membrane antigen positron emission tomography–computed tomography finding associated with a bounce phenomenon following low-dose-rate brachytherapy for prostate cancer. A single prostate-specific antigen test effectively ruled out the suspicion of local recurrence. While prostate-specific membrane antigen positron emission tomography–computed tomography is undoubtedly a valuable tool for detecting metastasis postoperatively, careful interpretation of local findings is essential owing to the potential for false positives. This consideration is vital when evaluating a patient with a rising prostate-specific antigen level after brachytherapy, to avoid premature initiation of salvage therapy.

Introduction

Prostate cancer is one of the most prevalent cancers in men, with over 1.4 million new cases estimated in 2020 all over the world [1]. Various radiotherapeutic approaches are available for the definitive treatment of prostate cancer, including low-dose-rate brachytherapy (LDR-BT), a well-established standard treatment for early-stage prostate cancer. LDR-BT offers improved oncological outcomes, a reasonable amount of irradiation, and favorable quality of life. First introduced by Grimm et al., it is often applied for likely organ-confined disease owing to its targeted high-dose delivery to the prostate with a rapid dose fall-off to surrounding tissues, thereby reducing the risk of complications [2]. Compared with radical prostatectomy, ¹²⁵I implantation offers advantages as a less invasive outpatient procedure with higher rates of sexual potency preservation and reduced acute morbidity such as urinary incontinence [3]. In approximately 30% of patients treated with LDR-BT, a prostate-specific antigen (PSA) “bounce phenomenon” (BP) might occur 1–2 years post-treatment, defined as a transient PSA rise of 0.2 µg/l above the nadir followed by a decline to or below the original nadir without intervention [4,5,6]. Notably, the PSA BP has been associated with favorable prognosis [7].

To date, there is limited experience examining false-positive prostate-specific membrane antigen (PSMA) positron emission tomography–computed tomography (PET-CT) findings related to the BP. Potential causes of local failure following brachytherapy remain uncertain. It could be challenging to achieve an optimal distribution of seeds within the prostate for adequate dose coverage or selecting appropriate candidates for monotherapy [8].

This report aims to evaluate the role of PSMA PET-CT in cases with the bounce phenomenon to give recommendations for follow-up protocols.

Case presentation

Our patient, a 67-year-old Caucasian (western European) male, presented in late 2020 for screening following a PSA elevation to 4.97 µg/l without any palpable nodules. Prostate MRI revealed a Prostate Imaging Reporting and Data System (PI-RADS) 5 lesion, prompting a transperineal biopsy on 15 December 2020. Histopathological examination confirmed prostate cancer (PCa) with Gleason score of 3 + 4 = 7a in 1 of 12 cores. The patient reported an International Prostate Symptom Score (IPSS) of 7/35 and a Quality of Life Score (QoL) of 1/6, following an operation via Millin approach in 2019. Given his elevated risk of incontinence, the patient opted against radical prostatectomy, choosing ¹²⁵I brachytherapy instead. This approach was deemed suitable as the case was classified as intermediate risk, considering that his PSA was below 10 µg/l, his Gleason score was 7a in only one core, and he maintained a favorable IPSS score. The patient underwent pre-implantation planning with ultrasound, and ¹²⁵I brachytherapy was successfully completed on 9 March 2021. The prescribed peripheral dose was 145 Gy. The postoperative course was uneventful. At 6 months post-procedure, the patient reported satisfactory urination with no occurrences of hematuria, incontinence, diarrhea, or hematochezia. PSA levels had decreased to 1.37 µg/l by 8 months post-implantation.

Approximately 6 months later, PSA levels slightly increased to 1.5 µg/l, which was not concerning at the time. However, a subsequent evaluation in November 2022 revealed a PSA rise to 4.16 µg/l characteristic of biochemical failure (BF) per the definition of American Society for Therapeutic Radiation and Oncology (ASTRO). This indicated a need for re-evaluation of patient management. A 298 MBq F-18-PSMA PET-CT scan identified a local recurrence within the prostate (Fig. 1), with no evidence of metastatic disease.

Fig. 1

Prostate-specific membrane antigen positron emission tomography–computed tomography showing a suspicious local recurrence of prostate cancer (red arrow A and B)

A follow-up PSA measurement was conducted after 4 weeks to measure the doubling time. Unexpectedly, this assessment revealed a decrease to 3.75 µg/l. In January 2023, a further decline was apparent to 2.68 µg/l. At 1.5 years later, his PSA was as low as 0.48 µg/l (Fig. 2). Considering this regressive PSA, additional therapies were deemed unnecessary.

Fig. 2

The patient’s prostate-specific antigen level trends

Discussion

Monitoring PSA levels post-therapy is essential during the follow-up of patients with prostate cancer [9]. Generally, a steady decline in PSA levels is expected following brachytherapy (BT); however, PSA kinetics may sometimes display a transient rise, known as the BP [7]. The biochemical underpinnings of this phenomenon remain unclear, although it is suggested that PSA shedding may result from cellular damage. Alternatively, the BP may be attributed to inflammation or the presence of residual prostate tissue [10, 11].

In terms of timing, the bounce phenomenon is generally reported to occur between 12 and 24 months post-BT, although it can emerge as early as 6 months or as late as 48 months following LDR-BT [12]. Biochemical failure (BF) after BT is observed in approximately 24% of patients and has been associated with improved overall survival [7].

A previously reported case showed almost identical characteristics of disease progression with an PSA increase approximately 30 months after BT [14]. In our case, biochemical failure (BF) occurred around 18 months post-LDR-BT, defined by the ASTRO criteria as a PSA increase of nadir + 2 µg/l, like following external beam radiotherapy.

This case illustrates a decision in agreement with the guideline to perform a PSMA PET-CT to assess potential tumor recurrence as a result of significant PSA increase. Despite imaging findings suggestive of localized recurrence in the prostate, follow-up PSA measurements subsequently showed a decrease, allowing us to avoid further investigations or even the need for salvage therapy. PSMA is a commonly used tracer for prostate cancer imaging, and it is essential to carefully assess and rule out nonspecific uptake in benign lesions [13]. This outcome was interpreted as a likely false-positive PSMA PET finding localized to the prostate.

Conclusion

Patients experiencing a PSA bounce tend to have improved biochemical relapse-free survival. The timing of the PSA rise after reaching the nadir can vary, occurring as early as 15 months or even up to 30 months following brachytherapy (BT).

This case highlights the critical need for cautious interpretation of PSMA PET-CT findings after low-dose-rate brachytherapy (LDR-BT) for prostate cancer. A transient PSA increase post-BT, even exceeding + 3 µg/l, does not necessarily indicate local recurrence. This consideration is vital when evaluating a patient with a rising PSA level after BT, to avoid premature initiation of salvage therapy.