Prostate cancer diagnosis is associated with an increased risk of erectile dysfunction after prostate biopsy
Correspondence: Kevin T. McVary, Department of Urology, 675 North St. Clair Street,Suite 20-150, Chicago, IL 60611, USA.
What's known on the subject? and What does the study add?
- There have been several studies that have suggested there may be a relationship between prostate biopsy and erectile function and LUTS. Previous studies have suggested a specific association between the type of local anaesthesia administered and/or the number of biopsies performed. Other studies have suggested an exacerbation of LUTS after prostate biopsy.
- The present study identifies a positive cancer diagnosis as a novel characteristic that may explain a relationship between biopsy and worsening erectile function.
- To evaluate prospectively the characteristics, erectile function and lower urinary tract symptoms (LUTS) of men undergoing prostate needle biopsy (PNBx).
Patients and Methods
- From 2008 to 2011, 134 men were prospectively administered the International Index of Erectile Function (IIEF), American Urological Association Symptom Index (AUA-SI), and quality-of-life (QoL) questionnaires before and after undergoing a single 12-core PNBx.
- Comparisons of IIEF and AUA-SI scores before and after PNBx, based upon baseline characteristics and prostate cancer (PCa) diagnosis, were performed.
- Univariable and multivariable logistic regression models were used to characterize predictors of change in IIEF scores.
- In the 85 men who fulfilled the inclusion criteria, there were no significant differences between the mean (sd) total pre-biopsy and the mean (sd) post-biopsy IIEF scores: 57.8 (12.9) vs 54.3 (17.2).
- Subgroup analysis showed that men who had biopsy-proven PCa had significantly greater changes in their post-biopsy IIEF scores compared with men without (−10.1 vs. 1.0; P < 0.001).
- After specific analyses of the IIEF domains in these groups we found significant decreases in every domain, including erectile function (P = 0.01). On multivariate analyses, only PCa diagnosis was associated with a significant change in IIEF (odds ratio 7.2; P = 0.003).
- There were no differences in AUA-SI or QoL scores in the overall population or in subgroups.
- Cancer diagnosis appears to have an adverse effect on the erectile function of men undergoing PNBx but no effect on LUTS. This study highlights a potential negative psychological confounder that may influence erectile function before the treatment of PCa.
- Additional prospective trials evaluating these relationships are warranted.
prostate needle biopsy
International Index of Erectile Function
quality of life
AUA Symptom Index
Sexual Health Inventory for Men
high grade prostatic intraepithelial neoplasia
Transrectal ultrasonography-guided prostate needle biopsy (PNBx) is the preferred diagnostic procedure for prostate cancer (PCa) detection after documentation of an abnormal serum PSA and/or DRE. Although possible side-effects include rare infection and sepsis in addition to common but self-limited haematuria and hematospermia, PNBx is generally considered a safe procedure [1, 2].
Several studies have suggested that PNBx is associated with erectile dysfunction (ED) and LUTS [3-8]. These changes have been attributed to periprostatic nerve anaesthesia and injury [4, 7], saturation PNBx [5, 7], and serial PNBx . By contrast, other studies have not found a relationship between ED and PNBx .
Prostate cancer diagnosis has been associated with psychological changes, anxiety and depression [9-12]. The diagnosis itself may represent a potent psychological stress that may increase the risk of stress-related health outcomes. Fang et al.  reported an increased risk of suicide and cardiovascular outcomes among men shortly after a diagnosis of PCa. While these negative health events may be related to the presence of advanced disease and/or age, it is unknown whether PCa diagnosis itself has an impact on quality of life, including erectile function.
There are many reported inconsistencies concerning the effect of PNBx on erectile and voiding function. To our knowledge, the influence of PCa diagnosis on ED and LUTS after PNBx has not yet been sufficiently evaluated using control groups; therefore, we tested the hypothesis that PCa diagnosis is associated with changes in ED and LUTS by prospectively evaluating the impact of 12-core TRUS-guided PNBx on voiding and erectile function.
Materials and Methods
Setting and Participants
The men included in the present study were prospectively screened for the presence of PCa in an outpatient clinical setting at Northwestern Memorial Hospital. The Northwestern Enterprise Data Warehouse was used to identify and obtain the clinical characteristics of men undergoing evaluation for the presence of PCa between April 2008 and August 2011. The study was approved by the institutional review board.
All men included in the present study underwent a single TRUS-guided 12-core PNBx. Indications for PNBx were determined by the urological surgeon's preference but included PSA value >2.5 ng/mL, increased PSA velocity >0.35 ng/mL/year and/or suspicious DRE. All patients received prophylactic oral antibiotics before PNBx and for 3 days after the procedure. All patients received TRUS-guided anaesthesia with 1% lidocaine (5 mL) injected into the angle between the prostatic gland and the seminal vesicles using a Chiba needle.
All men completed the AUA Symptom Index (AUA-SI), quality-of-life (QoL) , and International Index of Erectile Function (IIEF) questionnaires  at least 30 days before PNBx. The men completed these forms at their first follow-up visit between 1 and 48 weeks after PNBx. Men were excluded from the study if they did not complete an evaluation both before and after PNBx evaluation with AUA-SI and IIEF questionnaires, if they initiated treatment for cancer before their post-PNBx evaluation, if they underwent any other urological procedure before their post-PNBx evaluation, or if they had severe ED at baseline, defined by a pre-PNBx IIEF erectile function domain score (see below) of <10 points .
The AUA-SI and QoL scores were used to quantitatively assess LUTS , while the IIEF score was used as a tool to assess erectile function . For some analyses, the IIEF questionnaire was divided into five sub-domains, as previously described: erectile function (items 1–5 and 15), orgasmic function (9–10), sexual desire (11–12), intercourse satisfaction (6–8) and overall satisfaction (13–14). For other analyses, the Sexual Health Inventory for Men (SHIM-5) was used as an abbreviated form of the IIEF (2, 4, 5, 7 and 15).
The baseline clinical characteristics and post-PNBx features of all the men were recorded in the present study. Student's t-test and chi-squared tests were used to compare the changes in pre- and post-PNBx characteristics and scores in men with and without PCa on PNBx. In addition, univariate and multivariate logistic regression analyses were performed to determine which patient characteristics were predictive of a significant change in erectile function, as defined by a difference in total IIEF score of 5 or more points. A P value <0.05 was considered to indicate statistical significance. All statistical analyses were performed using SAS v. 9.2 (Cary, NC, USA).
A total of 134 men, who underwent PNBx, were prospectively evaluated using the AUA-SI and IIEF questionnaires. Of these, 49 (37%) were excluded because of baseline severe ED or because of PCa treatment before re-evaluation. The baseline characteristics of the 85 men who met inclusion criteria are shown in Table 1. In general, the men were ∼61 years old, had an elevated PSA level, a moderate degree of bothersome LUTS, and no significant ED (mean [SD] total IIEF: 57.8 [12.9]). No patient experienced an adverse event (e.g. UTI, sepsis, urinary retention, etc. ) after PNBx.
Table 1. Baseline characteristics of patients before biopsy*.
|Mean (SD) age, years|| ||61.0 (8.3)||64.8 (7.9)||59.6 (8.1)||0.009|
|Caucasian, n (%)|| ||48 (56)||14 (61)||34 (55)||0.02|
|African-American, n (%)|| ||13 (15)||6 (26)||7 (11)|
|Asian, n (%)|| ||4 (5)||2 (9)||2 (3)|
|Hispanic, Latino-American or other*, n (%)|| ||20 (24)||1 (4)||19 (31)|
|Mean (SD) PSA, ng/mL|| ||5.2 (3.4)||5.6 (2.9)||5.0 (3.6)||0.46|
|Mean (SD) AUA-SI score†||8–24||10.0 (7.1)||8.1 (7.4)||10.8 (6.9)||0.13|
|Mean (SD) QoL score†||0–6||1.9 (1.5)||1.4 (1.3)||2.1 (1.5)||0.04|
|Mean (SD) IIEF score‡||4–75||57.8 (12.9)||58.8 (11.0)||57.4 (13.6)||0.65|
|Mean (SD) SHIM-5 score‡||1–25||19.7 (5.4)||19.8 (3.8)||19.7 (5.9)||0.93|
Biopsy Results and Baseline Characteristics
Twenty-three of the men in the study cohort had PCa on PNBx, and the remainder (n = 62) had pathology results consistent with benign prostatic disease (n = 44, BPH, prostatic atrophy, or chronic inflammation; n = 18, high grade prostatic intraepithelial neoplasia [HGPIN]). Of the patients diagnosed with cancer, most had low grade disease (Gleason 6, n = 19; Gleason 7, n = 3; Gleason 8, n = 1). Comparison of the baseline characteristics of patients with and without PCa found that men with cancer were significantly older (Table 1). Analysis between men with biopsy-proven PCa and those without PCa showed no differences in pre-biopsy AUA-SI, QoL, total IIEF or IIEF domain scores.
The majority of patients were followed-up for re-evaluation of their LUTS and erectile function at ∼4.5 months after PNBx. Because of the possible need for definitive treatment, patients with PCa had a follow-up visit at a significantly shorter time interval compared with those without PCa (P < 0.001; Table 2). Regardless of cancer diagnosis, all men had relatively good overall erectile function after PNBx (mean [SD]: 54.3 [17.2] points); however, there was a significantly greater decrease in mean [SD] total IIEF score in men with a positive PNBx compared with men without cancer (−10.1 [10.8] vs. −1.1 [11.3]; P = 0.001). After analyses of IIEF domain scores a significantly greater decrease in all sub-domains in patients with PCa was found (Table 2).
Table 2. Characteristics of erectile function and LUTS after PNBx*.
|Post-PNBx evaluation, days||128.1 (91.6)||51.5 (64.9)||156.6 (83.6)||<0.001|
|IIEF score* after PNBx||54.3 (17.2)||48.7 (16.1)||56.3 (17.2)||0.07|
|SHIM-5 score* after PNBx||18.5 (6.8)||16.6 (6.0)||19.2 (6.9)||0.11|
|Change in total IIEF score||−3.5 (11.8)||−10.1 (10.7)||−1.1 (11.3)||0.001|
|Change in SHIM-5 score||−1.2 (5.1)||−3.3 (4.5)||−0.5 (5.1)||0.02|
|Change in erectile function domain score||−1.7 (5.6)||−4.3 (5.2)||−0.8 (5.5)||0.01|
|Change in orgasmic function domain score||−0.4 (3.3)||−1.4 (2.3)||0.0 (3.5)||0.04|
|Change in sexual desire domain score||−0.4 (1.8)||−1.3 (2.1)||0.0 (1.5)||0.01|
|Change in intercourse satisfaction domain score||−1.1 (3.0)||−2.4 (2.9)||−0.6 (2.8)||0.009|
|Change in overall satisfaction domain score||−0.0 (1.8)||−1.0 (1.3)||0.3 (1.9)||0.002|
|AUA-SI score† after PNBx||9.8 (7.0)||8.5 (7.7)||10.1 (6.8)||0.36|
|QoL score† after PNBx||1.8 (1.3)||1.6 (1.3)||1.9 (1.4)||0.46|
|Change in AUA-SI score||−0.3 (4.8)||0.1 (1.7)||−0.4 (5.4)||0.55|
|Change in QoL score||−0.1 (1.1)||0.2 (0.8)||−0.2 (1.1)||0.07|
Cancer diagnosis did not influence LUTS, as there were no significant differences in the overall AUA-SI or QoL scores after PNBx (Table 2). Interestingly, although HGPIN is often considered to be a precursor lesion to cancer, there were no significant differences in baseline clinical characteristics, before or after PNBx, or change in IIEF, AUA-SI or QoL scores between patients with HGPIN and controls (data not shown).
Univariable and Multivariable Analyses
Because of differences in the baseline characteristics, we performed multivariate analyses to determine whether any clinical variable (age, time before post-PNBx evaluation, PCa diagnosis) was associated with a significant change in erectile function after PNBx (Table 3). Only cancer diagnosis was significantly associated with a change in IIEF score (odds ratio [OR] 7.20; 95% CI 1.95–26.58; P = 0.003). Likelihood ratio testing found no significant difference between univariate and multivariate models. These analyses showed that PCa diagnosis was the best independent predictor of ED (OR 9.16; 95% CI 3.06–27.40; P < 0.001). There was no significant clinical variable on univariate or multivariate analyses that predicted a change in erectile function between patients with HGPIN and BPH (data not shown).
Table 3. Univariate and multivariate logistic regression analyses of clinical characteristics to predict a substantial (>5 point) change in total IIEF score.
|Days post-biopsy evaluation||–||–||1.00 (0.99–1.00)||0.36|
|Positive cancer biopsy||9.1 (3.1–27.4)||<0.001||7.2 (2.0–26.6)||0.003|
There has been significant controversy as to whether PNBx predisposes patients to ED and/or LUTS. While investigators have recently identified some of the factors that influence ED and urinary tract symptom outcomes (e.g. local anaesthestic, number of biopsies, time after the procedure, etc.) [3-5, 7, 8], to our knowledge no study has addressed these issues in relationship to PCa diagnosis. Reasons for this include the fact that the urinary symptoms and erectile function of most men are evaluated and treated after a PCa diagnosis, and that data regarding ED and LUTS are not systematically obtained with validated questionnaires by most screening studies or cancer registries. The available data suggest that the diagnosis of PCa has an impact on many aspects of a man's life and may even increase stress-related events; however, it was previously unknown whether the knowledge of a PCa diagnosis can influence the erectile function and/or severity of LUTS after PNBx.
In the present study, we found a relationship between PCa diagnosis and ED, but not between PCa diagnosis and LUTS. On multivariate analysis we found that PCa diagnosis, but not age or time after PNBx, was significantly associated with a meaningful decrease in IIEF score. Specifically, men with a positive biopsy were 9.1 times more likely to have a decrease of 5 or more points in their total IIEF compared with men without cancer.
It has been suggested that men may experience ED after PNBx. It appears that for the majority of these men, this decrease in erectile function is transient and returns to baseline by 4–6 weeks after the procedure . In fact, only a small percentage of men (8–10%) will continue to experience ED more than 3 months after PNBx [8, 16]. This ED has been attributed to periprostatic nerve block and/or number of biopsy cores obtained [5, 7]. In addition, recent data suggest that ED may be related to the number of repeated biopsies . In the present study, all patients received a single 12-core PNBx. Although there was a significant difference in the timing of re-evaluation between men diagnosed with PCa and those with benign disease on biopsy, we do not believe that this explains the differences in erectile function that were observed between the groups. This is supported by the fact that most men with a positive biopsy were re-evaluated at ∼7.5 weeks after PNBx (Table 2), a time when the effects of periprostatic anaesthetic agents should be diminished [4, 7]. In addition, our multivariate analyses found no significant associations between the timing of erectile function assessment and a meaningful change in IIEF score. Taken together, although we cannot completely exclude the influence of the timing of re-evaluation on the groups, the data suggest that this influence is not a significant contribution.
There is increasing awareness of the potential psychological impact of cancer diagnosis. PCa diagnosis has been associated with increased anxiety and rates of depression [9, 11, 12, 17]. In addition, recent studies have found that the diagnosis of PCa is associated with an increased risk of suicide [10, 18, 19]. Furthermore, Zisman et al.  have found that men experience sustained anxiety after biopsy when they are concerned about PCa, while this stress and anxiety decreases when PCa is not detected. The results of the present study suggest that anxiety may persist in men with a PCa diagnosis and may be manifested as erectile and sexual dysfunction, but it is important to note that while most of these men experience significant changes in sexual function, desire and satisfaction, these changes are relatively mild in nature.
It has recently been shown that there is a lack of agreement between recalled IIEF scores and a patient's actual IIEF scores before PCa treatment [20, 21]; therefore, it has been suggested that a man's erectile function should be assessed before definitive treatment. The results of the present study expand on this concept and suggest that this evaluation should be performed before PNBx to accurately portray the patient's erectile function before PCa diagnosis and treatment. Finally, the results of the present study also have profound implications for men who undergo repeated prostate biopsies as part of an active surveillance protocol. In men with PCa, serial prostate biopsies have been shown to worsen ED , yet the present results suggest that the psychological impact of having PCa may also worsen erectile function.
Over short time intervals, it has been suggested that some men may experience an increase in LUTS after PNBx . Most men in the present study were evaluated at time intervals >6 weeks, and, accordingly, it is not surprising that we found no significant differences in the degree of bothersome LUTS after PNBx. Although there was a relationship between PCa diagnosis and erectile function, there was no correlation between the pathological results and changes in LUTS. This suggests that any psychological component associated with a PCa diagnosis does not appear to exaggerate the degree of urinary symptoms.
There are several limitations of this study that deserve mention, including our relatively small sample size. Additional prospective studies in larger populations are warranted. Similarly, because of clinical practice patterns, timing of follow-up evaluation was not standardized. While statistical analyses did not suggest that time from biopsy was a factor that influenced changes in erectile function, it should be evaluated using a more systematic methodology. Finally, while the results of the study suggest that there is a psychological impact of a PCa diagnosis on erectile function, we did not specifically interview the patients regarding their anxiety and/or stress levels, and future studies correlating these findings are also warranted.
In conclusion, the present results confirm previous findings showing that a single 12-core TRUS-guided PNBx is not associated with chronic impairment of erectile function; however, men who are diagnosed with PCa experience a significant decrease in their total and individual domain IIEF scores. Based on these findings, we suggest that a patient's evaluation of his erectile function should be obtained before undergoing PNBx. In addition, further studies investigating the extent of the psychological influence on erectile function after a diagnosis of PCa should be performed.
Supported in part by the Urological Research Foundation, National Cancer Institute Prostate SPORE grant (P50CA90386-05S2), SMSNA Research Fellowship Grant, Havana Day Dreamers Foundation and the Robert H. Lurie Comprehensive Cancer Center grant (P30 CA60553).
Conflict of Interest