Hematospermia, defined as gross blood in the ejaculate (1), is an uncommon condition in the elderly population (< 1%) (2, 3). It is bothersome to men and their partners but is generally a benign finding that resolves on its own. Standard management is reassurance (1, 4). The most common etiology of hematospermia in the elderly population is iatrogenic including prostate biopsy (5) and prostatic fiducial placement (6). Hematospermia generally resolves in days to weeks (5). The blood is commonly bright red immediately post-procedure but can appear brown in color for months to years after the procedure as prostatic hematomas slowly resolve.

Bothersome ejaculatory symptoms following prostatic irradiation include reduced fluid volume, ejaculatory pain and hematospermia (7, 8). The etiology of post-radiation hematospermia is unclear but may involve inflammation of the seminal vesicles, vas deferens or ejaculatory ducts ( Figure 1 ). It occurs months to years after treatment and generally resolves on its own without interventions but may persist in some men (7, 8). Up to 25% of patients report it following prostate EBRT and/or brachytherapy (7, 8). 5-alpha reductase inhibitors are an effective treatment for hematospermia (9) but they may cause duration-dependent decreased libido (10). This study sought to evaluate the incidence, duration, and resolution of hematospermia in patients following stereotactic body radiation therapy (SBRT) for prostate cancer.

227 patients on a prospective quality of life study (IRB#: 2009-510) with baseline ejaculatory capacity treated with prostate SBRT at Georgetown University Hospital from 2013 to 2019 were included in this analysis ( Table 1 ). They were ethnically diverse with a median age of 65 years (interquartile range, 62-68 years). The median pre-treatment total serum testosterone level was 373 ng/dL (interquartile range, 287 - 483 ng/dL). When stratified by D’Amico risk group, 45 patients were low-, 179 intermediate-, and 5 high-risk ( Table 1 ). For treatment, 90% of patients received 36.25 Gy in five 7.25 Gy fractions. The minimum length of follow-up was 2 years and no patient initiated androgen deprivation therapy prior to SBRT or in the first two years following radiation therapy.

The prevalence of hematospermia prior to and after SBRT treatment is shown in Table 2 . At the time of the initial SBRT treatment, no patient reported hematospermia. Levels of patient reported hematospermia increased significantly following treatment ( Table 2 ), with 3% of patients reporting blood in the ejaculate at 3 and 6 months post-SBRT (p < 0.0001). While a low level of hematospermia was seen throughout the second years of follow-up, our 24-month prevalence of hematospermia was approaching baseline values ( Table 2 ). The overall cumulative incidence of hematospermia two years post-SBRT was 5.6% (14 patients) ( Figure 2 ). The mean time to developing hematospermia was 9 months post-SBRT. 70% of the patients were treated with 5-alpha reductase inhibitors. The mean duration was 3 months (range 3-12 months). Figure 3 depicts a Swimmer’s plot of hematospermia prevalence and 5-alpha reductase inhibitor utilization.

To our knowledge, this is the first study to report the hematospermia incidence following prostate SBRT. Hematospermia was uncommon at any time point and transient in most cases. The prevalence of hematospermia peaked at 6-9 months. From our clinical experience, hematospermia was rare greater than two years post-SBRT. These results appear similar to brachytherapy (7, 8). Hematospermia is a known complication of conventionally fractionated IMRT (1), however we could not identify evidence for the incidence in the current literature. Future work should compare the incidence of hematospermia following conventionally fractionated IMRT and SBRT.

Post-SBRT hematospermia is likely secondary ejaculatory duct inflammation (1, 4). Inflammation of the ejaculatory apparatus is a common cause of hematospermia (1, 4). Etiologies include epididymitis, urethritis, prostatitis and seminal vesiculitis. The timing of hematospermia following SBRT is similar to the phenomena of late urinary symptom flare (17). Late urinary symptom flare is a transient increase in urinary symptoms seen several months following SBRT (17). It resolves on its own with time with a percentage of patients requiring a short course of anti-inflammatory medications (17). The exact etiology is unknown but likely involves post-RT inflammation of the bladder neck/prostatic urethra (18, 19).

5-alpha reductase inhibitors reduce hematospermia by reducing blood flow to the prostate (9). The Optimal Length of finasteride treatment is unknown. In general, we prescribe for three to six months then discontinued due to adverse sexual side effects. Hematospermia recurred in 1 patient but responded to a second course of 5-alpha reductase inhibitors ( Figure 3 ).

Hematospermia is a bothersome self-limiting symptom experienced by a small percentage of men following prostate SBRT. 5-alpha reductase inhibitors may lead to quicker resolution of bothersome hematospermia.

As per the wishes of the patients, the patient dataset is only available to those conducting research at the Georgetown University Medical Center. Requests to access the datasets should be directed to SPC9@gunet.georgetown.edu.

The studies involving human participants were reviewed and approved by Georgetown University Institutional Review Board. The patients/participants provided their written informed consent to participate in this study.

SaS was the lead author and participated in data collection and manuscript revision. TS and MC also contributed equally to SiS for this work and participated in data analysis, manuscript drafting, table/figure creation, and manuscript revision. AP, JC, BC, and RH aided in review and revision of the manuscript. SS is a senior author who organized the data and participated in its analysis. SC was the principal investigator who initially developed the concept of the study and the design, aided in data collected, and drafted and revised the manuscript. All authors contributed to the article and approved the submitted version.

This work was supported by The James and Theodore Pedas Family Foundation. The Department of Radiation Medicine at Georgetown University Hospital receives a grant from Accuray to support a research coordinator. We gratefully acknowledge the grant R01MD012767 from the National Institute on Minority Health and Health Disparities (NIMHD), NIH to SC.

SC serves as clinical consultants to Accuray Inc.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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