False-positive prostate cancer markers in a man with symptomatic urethral Chlamydia trachomatis infection

INTRODUCTION

Sexually transmitted infections (STIs) have been proposed in the development of prostate cancer, ¹ conceivably mediated via an inflammatory process in the prostate gland caused by an ascending bacterial infection. ¹

Prostate cancer (PrCa) is very common in developed countries, accounting for 29% of all incident cancers in the USA. ² Prostate-specific antigen (PSA) is used to screen for PrCa, but results in a significant proportion of negative biopsies. Only a prostate biopsy test can confirm a PrCa diagnosis. Recently, the US FDA approved the prostate cancer antigen 3 test (PCA3 gene measured in urine sediment after prostatic massage), to provide assistance in the diagnostic process. ³

We report on a case of a man from a PCA3 pilot project in St Petersburg, Russia, who had a symptomatic urethral Chlamydia trachomatis (CT) infection resulting in inflammation of the prostate and increased levels of both PSA and PCA3.

CASE REPORT

A 38-year-old white man presented to a urologist's office at the University Clinic in St Petersburg in October 2010 with a history of unprotected sex. He had been experiencing lower urinary tract symptoms and erectile dysfunction for more than three months.

The patient was in a steady relationship with a woman but reported unprotected sex with another woman 3.5 months ago, which resulted in urethral discharge and itching four days after the unprotected intercourse. One week later urgency, frequency, dysuria and nocturia replaced the urethral symptoms. After three weeks, pelvic pain, scrotal discomfort and erectile dysfunction appeared. The patient had no past history of prostate disease but reported a family history of malignancies of unknown origin among several relatives. This prompted him to request PrCa screening. His past sexual history included more than 100 sex partners in his life-time and a CT infection successfully treated two years before this event.

Physical and digital rectal examinations (DRE) were performed with no visual symptoms but abnormal (increased hardness) DRE was present. Blood tests and urogenital samples from the man, having abstained from any form of sex for 3–5 days and from urination for 3–4 hours before collection, were taken to check the serum PSA level and exclude STIs. The two-glass test was performed to separate inflammation in the distal urethra and upper urogenital tract. ⁴

CT infection was detected by a reverse transcriptase-polymerase chain reaction assay (Central Research Institute of Epidemiology, Moscow, Russia) in St Petersburg and confirmed by the Laboratory of Immunogenetics (VU University Medical Center, Amsterdam, The Netherlands), using the CE-IVD-certified Presto CT-NG Assay (Goffin Molecular Technologies, Beek, The Netherlands). No HIV or other STIs were detected.

The prescribed course of doxycycline (Unidox Solutab, Astellas Pharma Europe B.V., the Netherlands) at a dose of 100 mg twice a day for seven days was successful with subsequent cessation of symptoms. On repeat laboratory examination no CT infection was detected.

Serum PSA tests showed abnormal results both before and one month after the antibiotic treatment (Table 1). This prompted a PCA3 test. The main diagnostic tools to diagnose PrCa include DRE, serum concentration of PSA and prostate biopsies. ⁵ The novel PCA3 assay has been recommended to be used to guide decision on biopsy-taking in men with an elevated total PSA level from 2.5 up to 10 ng/mL and no previous biopsy. ³

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Table 1

Abnormal prostate cancer markers in a man with symptomatic urethral Chlamydia trachomatis infection

	First visit	Follow-up visits
		1 month	3 months
CT infection, tested by RT-PCR	Positive	Negative	Negative
Symptomatic	Yes	No	No
Digital rectal examination	Abnormal	Abnormal	Abnormal
Leukocytes, per hpf	30–40	0–2	0–1
PSA test, (normal 0–4 ng/mL)	13.9 abnormal	9.8 abnormal	1.5 normal
PCA3 test, (normal <35)		38 abnormal
Prostate biopsy		Negative

The collection of two urine samples after a DRE was performed following the manufacturer's protocol (PROGENSA^® PCA3, Gen-Probe, San Diego, CA, USA). The first sample was used for PCA3 detection (The Doctors Laboratory, London, UK) while the second was stored at −20℃ prior to HPV testing at Karolinska Institutet in Stockholm, Sweden using a reference method from the World Health Organization human papillomavirus (WHO HPV) LabNet global reference laboratory, a proficient ^6,7 Luminex (Bio-Rad, Hercules, CA, USA) assay. None of the 14 oncogenic or 22 non-oncogenic HPV types tested for were detected.

Surprisingly, the PCA3 test was elevated. According to standard practice, a TRUS-guided 18-core prostate biopsy was taken but histological examination revealed no evidence of PrCa, only prostatic inflammation.

DISCUSSION

Although the PCA3 gene test is a promising screening tool and CT-induced inflammation has not been previously described as a cause of increased PCA3, we describe in the present case that CT infection can cause increases in both PCA3 and PSA levels, where PSA levels normalized a few months after successful CT treatment. As the suggested age for PrCa screening is no earlier than 40 years ⁵ and CT is more commonly acquired by younger sexually active men, CT-induced inflammation is not likely to be common as possible cause of false-positive PrCa markers. Although a history of STIs has been associated with increased PrCa risk, large prospective studies in several Nordic countries have instead found that CT seropositivity is consistently associated with decreased PrCa risk. ⁸ That antibiotic treatment against CT might be protective by reducing inflammation was proposed as a possible explanation. ⁸ Our case suggests that further studies to evaluate the time course of STIs, STI treatments and chronic inflammation in the prostate on PrCa markers and risks are warranted.

CONCLUSION

Ongoing CT infection of the prostate should be considered among possible causes of false-positive PrCa markers, including PCA3, in younger, sexually active men.