Prostate-specific antigen (PSA) bounce following salvage radiotherapy to the prostate bed in a patient with prostate cancer post-prostatectomy

Abstract

We present a case of prostate-specific antigen (PSA) bounce in a 76 year old man who underwent salvage radiotherapy to the prostate bed following biochemical relapse 6 years post-radical prostatectomy for a T2N0 Gleason grade 3 + 3 prostate adenocarcinoma; 10 months following completion of salvage radiotherapy for biochemical PSA recurrence of 0.2 μg/L. Following undetectable results (<0.03 μg/L), his PSA rose from 0.04 to 0.3 μg/L with no evidence of prostate cancer recurrence before returning to undetectable levels without medical intervention. This PSA ‘bounce phenomenon’ is well described following radiotherapy to an intact prostate and has been proposed to be the result of a late fibrotic effect on irradiated prostate tissue. To our knowledge, this is the first case published describing the effect in the post-prostatectomy setting. It highlights the importance of serial PSA monitoring to confirm biochemical relapse before committing the patient to androgen deprivation therapy (with its inherent risks and side effects).

Background

We present a case of a 76 year old man who displayed a PSA ‘bounce phenomenon’ following salvage radiotherapy for PSA recurrence post-prostatectomy. The PSA bounce effect, defined as a temporary rise in the PSA level without prostate cancer recurrence, is seen following radical radiotherapy (including external beam, brachytherapy, and stereotactic ablative radiotherapy) to the prostate [1–3]. Awareness of this effect is important as it may falsely indicate biochemical relapse leading to unnecessary initiation of androgen deprivation therapy. Serial PSA measurements are needed to confirm biochemical relapse.

Our case suggests that this effect can also be seen in patients who have undergone previous radical prostatectomy and PSA bounce should be considered in patients with a PSA rise following salvage radiotherapy.

Case presentation

Our patient is a 76-year-old gentleman who was diagnosed with a T2N0M0 Gleason grade 3 + 3 prostate adenocarcinoma in 2010. PSA at time of diagnosis was 4.8 μg/L (Cobas Total PSA assay, ECLIA, MODULAR ANALYTICS E170 analyser, Roche).

He had a radical prostatectomy aged 66 on 01/07/2010 and histology confirmed Gleason grade 3 + 3 prostate adenocarcinoma in both lobes pT2cNx with evidence of perineural invasion but no lymphovascular invasion or capsular breach. The apical margin was involved but no clear evidence of circumferential margin involvement.

The patient recovered very well post-prostatectomy with good urinary function and an undetectable PSA (<0.03 μg/L) until July 2012 when a PSA of 0.07 μg/L was detected (see Fig. 1 for PSA trend). His PSA was then slowly increased to 0.2 μg/L in February 2016 at which point he was offered salvage prostate bed radiotherapy.

Fig. 1.

PSA trend over time. PSA reading of 0 represents “undetectable values” (<0.03 μg/L)

He then received 66 Gy in 33 fractions over six and a half weeks to the prostate bed using volumetric arc intensity-modulated radiotherapy (see Fig. 2 for dose distribution) which he competed May 2016 without any significant side effects. No evidence of macroscopic prostate bed or lymph-node recurrence was seen on the planning CT scan.

Fig. 2.

Prostate bed radiotherapy plan isodoses

His post-radiotherapy PSA was 0.06 μg/L and it fell to 0.04 μg/L by December 2016.

In March 2017, his PSA rose suddenly to 0.3 μg/L and then fell back to <0.03 μg/L in August 2017 with a very slight rise from October 2018 (0.016 μg/L) coinciding with a change in PSA assay (ARCHITECT Total PSA Assay, CMIA, Architect analyser, Abbott) testing sensitivity (<0.01 μg/L) but no evidence of biochemical relapse and ongoing suppressed PSA <0.03 μg/L.

Outcome and follow-up

Our patient remains alive and well, and continues on our remote PSA monitoring follow-up programme with no biochemical evidence of disease recurrence. His PSA is checked every 6 months, and if further PSA rises are detected, he will be referred back to the oncology clinic for review. As of May 2020, his PSA remained undetectable at <0.010 μg/L.

Discussion

The PSA ‘bounce’ phenomenon is well described after radiotherapy to an intact prostate using brachytherapy or external beam radiotherapy [1–3]. It has also been described following stereotactic ablative radiotherapy (SABR) [4]. It is defined as temporary self-limiting rise in the PSA level by more than 0.1 μg/L without prostate cancer recurrence [5]. It usually occurs 12–18 months post-radiotherapy which distinguishes it from biochemical recurrence which tends to occur later at 22–41 months [2, 6, 7]. There are numerous theories regarding its aetiology including radiation prostatitis, late radiotherapy induced fibrosis, physiological inter-assay variability, and, more recently, anti-tumour immune response [8–10].

It has been suggested that this PSA bounce phenomenon may be associated with better biochemical disease-free survival [11].

Some series report 15–33% of patients experiencing at least one PSA bounce post radiation treatment with low Gleason grade 3 + 3 and younger age associated with a higher rate of PSA bounce phenomenon [7, 11].

Awareness of the PSA bounce effect is important as it may be incorrectly construed as biochemical failure and lead to the initiation of androgen deprivation therapy (ADT) with the associated psychological distress caused by the diagnosis of cancer relapse. ADT can also have long-term side effects in particular on cardiovascular disease risk and clinicians must, therefore, be certain the biochemical failure has occurred, rather than benign PSA bounce effect [12].

Our patient demonstrates that the PSA bounce effect can be seen following prostate bed radiotherapy, presumably due to similar reactions in macroscopic residual prostate tissue happening in microscopic residual disease. The fact the PSA was undetectable for several years post-prostatectomy would again suggest no residual macroscopic disease.

The lack of any significant residual prostate tissue post-prostatectomy which would be able to produce a PSA bounce phenomenon may be a reason why PSA bounce post-prostate bed radiotherapy is rare. It would also explain the low level of the PSA bounce seen in our case.

To our knowledge, this is the first report of PSA bounce phenomenon after radiotherapy to the prostate bed post-prostatectomy. As PSA bounce phenomenon can occur in a significant minority of prostate cancer patients post-radiotherapy to prostate tissue, it is important to consider in this setting.

Holding off androgen deprivation therapy in patients with rising PSA post-prostate bed radiotherapy until clear evidence of repeated PSA rises or metastatic disease could avoid unnecessary treatment in a group of patients which have an otherwise very good prognostic outlook.

Take home message

• PSA bounce effect is a benign fluctuation in PSA value.

• It is well described following radiotherapy to an intact prostate.

• We describe PSA bounce effect following prostate bed salvage radiotherapy.

• Serial PSA testing should guide androgen deprivation therapy initiation.

Funding

The authors have received no financial support for the research, authorship, or publication of this manuscript.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare for this manuscript.