Prevention and Management of Post Prostatectomy ED
Prevention and Management of Post Prostatectomy ED
As correctly stated by the International Consultation on Sexual Medicine (ICSM) committee, the first concept in terms of post-RP ED prevention is that, well before RP, the patient and, whenever possible his partner, has the inalienable right to be given realistic expectations regarding his postoperative erectile and sexual functioning. This will help anyone (i.e., physicians and patients) understanding how to start with the prevention of damage and the subsequent EF recovery, thus reducing the plausible false expectations and subsequent frustrations.
Most of the historical data refer to open RP; overall, the incidence of post-RP ED varies between 14% and 90%. As a whole, the incidence of reported postoperative ED is extremely discrepant among series, because of a great variation in the nature of the populations studied and the modality for data collection and reporting; the great inconsistency in the definition of what is considered a normal EF before surgery and what one may consider a normal erection after RP emerged as the key problem in almost all these studies. The results of the meta-analysis conducted by Tal et al. clearly stated that most of the published literature does not meet strict criteria for reporting post-EF recovery. The same meta-analysis found as many as 22 different definitions of favorable EF outcome. In this context, the overall fixed effects EF recovery rate was 58% (95% CI: 56–60%), with significant heterogeneity among effect impacts. Similar results were also discussed by Burnett et al. as a side analysis of outcomes assessed as part of an update of the American Urological Association (AUA) PCa guidelines. They reported how, in many instances, only qualitative and subjective determinations were used, thus interpretable at best as erectile ability insufficient, somewhat functional, or regularly sufficient for sexual intercourse. Moreover, it has been well-observed that EF data from the largest series often refer only to a small fraction of the total RP population since the evaluable number of patients often had represented only a fraction of the total exposed to surgery. Therefore, these are some of the most significant obstacles to the accurate interpretation of the incidence and prevalence of post-RP ED, mainly when considering all study types and all technical approaches available.
Laparoscopic and, even more, many large series of robotic-assisted approaches are mature enough and have demonstrated that EF outcomes are at least equivalent to those obtained with open RP. Still, a number of limitations for a correct and objective interpretation of results are also discernible in the literature that deals with this type of surgery.
The literature clearly highlights that preoperative EF is an important predictor of EF recovery after RP. To this specific purpose, it is mandatory to verify how the definition of baseline EF was done; indeed, numerous assessment modalities have been reported in the literature, thus including patients subjective self-reports, partner-corroborated function and validated psychometric instruments. Overall, we consider of critical importance the analysis made by Mulhall, who reported that a clear mention of baseline EF was only given in only 16 (66%) of 24 studies considered as representative of the experience of large volume worldwide centers. In this context, it was a further recommendation of the ICSM committee that clinicians should use a validated psychometric instrument, with recognized cut-offs for normalcy and severity, during the pre and postoperative evaluation of their patients. Either the International Index of Erectile Function (IIEF) or the Sexual Health Inventory for Men (SHIM)—with cut-off scores for 'normal' EF of 26 and 21, respectively—keep their clinical usefulness to define EF.
Baseline EF assessment is still problematic and the most reliable timing of this assessment is even more poorly defined: on the one hand, some patients might overestimate their previous EF; on the other hand, proximity to the surgery may reduce the sexual activity/desire of either the patient, his partner or the couple as a whole. PCa diagnosis, cancer-related or treatment-associated psychological distress may also significantly impair the real-time assessment of EF immediately prior to RP; therefore, this "late" real-time evaluation might not be fully representative of the patient's true sexual functioning. Kim et al., for instance, reported that in order to accurately assess the pre-diagnostic baseline EF in candidates for RP, the psychometric tools should be administered before prostate biopsy rather than before robot-assisted laparoscopic radical prostatectomy (RARP) since cancer diagnosis-related symptoms and depression can ultimately affect sexual function and index scores.
Overall, the definition of ED of the National Institutes of Health (NIH) was not designed to be applied to a specific population, and even less for a complex population such as the patients undergoing RP; this is of particular importance today because such a widely-used definition does not include any mention of the role or use of erectogenic aids or other assistance, which are hugely suggested in PCa patients after surgery. Adequate knowledge of the potential use of any preoperative or post-RP erectogenic aid and what proportion of data in any given series was collected from patients using these agents are of relevant importance to allow an accurate interpretation of the findings. These further aspects make giving a proper definition of postoperative EF extremely difficult.
A further crucial aspect is the definition of what the patient can actually expect after surgery, that is the concept of regaining EF "back to baseline"; indeed, a significantly small proportion of preoperative potent men may spontaneously return to baseline EF after RP. Having in mind the clear intention of limiting patient false expectations, clinicians have to comprehensively discuss the objective of regaining an erection equivalent to that prior to RP, especially using data from their own RP population. If we start from the NIH definition of ED, the focal point would become the fact that adequate postoperative erections may be "at least" sufficient for satisfactory sexual performance. Mulhall reported that adequate EF was defined as the "ability to have successful intercourse by patient self-report" in 42% out of the series taking into consideration in his own meta-analysis. Unfortunately, overall 37% of the series did not even report how the authors define adequate erections. More recently, Nelson et al. considered 24-mo follow-up data from 180 men submitted to RP; of them, when including men who were using a PDE5I at 24 months, 43% got back to their baseline EF, while 22% of the whole cohort returned to the baseline EF without the use of any PDE5I. For this group, there was a significant difference by age, which remained a significant predictor (OR =6.25, P<0.001) at multivariable analysis.
In an attempt to combine the two concepts of getting EF "back to baseline" and being able to achieve erections sufficient for satisfactory sexual intercourses, as originally suggested by the NIH, it becomes important to consider the potential misinterpretation of the established cutoffs for normalcy as well as the grading of ED severity (mild, moderate and severe) of both the IIEF-EF domain and SHIM. Indeed, using the usual cutoffs for normal function—which are generally considered for the broad-spectrum ED population—might be overly stringent for post-RP populations; indeed, there are patients that still consider themselves to be fully functional while having lower scores. In order to try and define a cut-off value as close as possible to the real-life setting, Briganti et al. considered a relatively small cohort of preoperatively fully potent patients (IIEF-EF ≥26) treated with retropubic BNSRP at a single institution and suggested that a cut-off of IIEF-EF ≥22 may represent a reliable score for defining EF recovery after BNSRP.
Another crucial aspect that has to be discussed with the patient is the issue of the chronology of events of recovery and the post-operation period. Burnett et al. rightly commented that in the modern era of RP the majority of men usually achieve resumption of all physical activities, recovery of urinary control and normalization of bowel function within a few months after surgery. In contrast, postoperative EF continues to improve over time, at least up to 24 months and in some series up to 48 months post-RP. Overall, although the data are not entirely unambiguous, RARP seems to promote a faster EF recovery as compared to open RP.
Time of erection recovery does not uniformly occur in all cases and a number of predictors of EF recovery have been identified, including patients' age at surgery (i.e., the younger the better), better preoperative EF, extent of neurovascular bundle preservation and erectile hemodynamic changes after surgery. In this context, surgery (i.e., type, quality, surgical volume and the actual NS approach) probably emerges as the most compelling aspect. In this context, Tal et al. reported that BNSRP was certainly associated with higher EF recovery (P=0.01) as compared with UNSRP. When dealing with preservation of the neurovascular bundles (NVB), most patients—and, unfortunately, a number of clinicians—do not have an adequate understanding of the concept of NS; indeed, they think that NS always leads to complete preservation of the nerves and, consequently, to the absence of any transient postoperative ED. This is not correct; even when surgeons believe that they have achieved complete BNS, there is inevitably some trauma to the nerves so, in order to prevent false and unrealistic expectations, clinicians have to provide patients with a realistic time frame for EF recovery. Experts suggest that a potential period of 6–36 months would be necessary, although most men have a functional recovery within 12 and 24 months since RP. Katz et al. showed that the recovery of functional erections in the early postoperative phase, especially without the need for PDE5Is, is a good prognostic indicator for EF at 12-mo assessment. Thus, it should be stated with the patients that the ability to have either a spontaneous or a pharmacologically-assisted functional erection (namely PDE5I-sustained) within three months of RP is an excellent prognostic indicator. No less important, the fact that it can take a long time until the first spontaneous erections occurs should not lead the physician to wait inactively: indeed, the patient should start with supportive medication therapy for EF recovery as early as possible.
As a further major aspect, the clinician should also debate issues concerning the quality of erection. In this context, one of the parameters which have to be taken into account is the hardness of erection, mostly defined using a 4-point scale such as the Erectile Hardness Score (EHS). Indeed, although a patient may postoperatively have functional erections, which allow him to have sexual intercourse, a more or less severe loss of erection hardness may lead to erection dissatisfaction for the same man. Consequently, he might deserve erectogenic compounds for greater erection hardness, or even a second or third line treatment, if that gentleman was already using an erectogenic medication. A second parameter is the consistency of functional erections, which means how consistently a functional erection can be obtained. Data regarding RP populations are still lacking.
Prevention and management of EF in patients treated with RP is necessarily heavily predicated upon a careful choice of the correct patient for the correct type of surgery: clinicians should comprehensively discuss the recognized predictors of EF recovery with any candidate for RP, and all patients with PCa who might benefit from RP as a curative treatment should also receive an appropriate counseling regarding (I) the possibility of being subjected to a RP [see, in this context, the most updated EAU guidelines]; and, (II) the possibility of being subjected to a NSRP or, conversely, the need to be treated with NNSRP, according to the baseline oncological condition. Imbimbo et al. investigated factors related to patients' desire to preserve post-RP sexual activity and those determinants for surgeons' final decision to eventually perform a NSRP. Overall, 69% of the patients were preoperatively interested in preserving their sexual activity. Of the entire cohort, 13% were not interested but suitable for a BNSRP, 18% were neither interested nor suitable, 39% were both interested and suitable, but up to 31% were interested but not suitable. Age and normal preoperative sexual function parameters emerged as independent determinants of patients' desire to preserve postoperative sexual functioning. Overall, 13% underwent an UNSRP and 36% a BNSRP. Along with oncological indications, age and patients' desire to preserve sexual activity were among the main independent determinants of surgeon's final decision for a NSRP. Overall, findings from this study underlined the existence of discrepancies among patient's desire to preserve postoperative sexual function, guideline indications to NSRP, and surgeons' final decision for a NS approach.
Therefore, once established that the patient can eventually receive a NSRP, counseling should focus on the patient's baseline functional situation along with the potential predictors of post-operative EF recovery. Preoperatively, these factors necessarily include age at surgery, baseline EF, body mass index and comorbidities. Likewise, type of surgery, coupled with surgical volume and surgical skill, and NS status achieve the role of significant contributors to EF recovery. Briganti et al. developed a preoperative risk stratification tool aimed at assessing the probability of EF recovery after open BNSRP. They used routinely-available baseline data, such as patient age and preoperative EF, as psychometrically objectified with the IIEF; moreover, as a proxy for general health status, the authors scored health-significant comorbidities using the Charlson Comorbidity Index (CCI). For the specific purpose of the analysis, CCI was categorized as a score of 0, 1, or ≥2. The resulting tool was able to stratify patients into three groups according to the relative preoperative risk of post-RP ED: low (age ≤65 years, IIEF-EF ≥26, CCI ≤1), intermediate (age 66–69 years or IIEF-EF 11–25, CCI ≤1), and high risk (age ≥70 years or IIEF-EF ≤10 or CCI ≥2). More recently, Novara et al. applied the same risk stratification categories to a relatively small cohort of patients treated with BNS RARP who were assessed at a minimum 12-mo follow-up; according to the risk-group stratification proposed by Briganti et al., the 12-mo EF recovery rate was 82%, 57% and 29% in the low-risk, in the intermediate-risk, and in the high-risk group, respectively (P<0.001).
Overall, prevention and management of postoperative EF necessarily pass through rigorous selection of the patients who may benefit from RP: the clinician must clearly inform the patients that the NS approach does not invariably ensure the recovery of erections at all; moreover, since this type of surgery may be potentially subjected to a number of sequelae, a NS approach should be reserved for young patients without significant comorbidities and an adequate preoperative EF.
Prevention of Post-RP Erectile Dysfunction (ED)
As correctly stated by the International Consultation on Sexual Medicine (ICSM) committee, the first concept in terms of post-RP ED prevention is that, well before RP, the patient and, whenever possible his partner, has the inalienable right to be given realistic expectations regarding his postoperative erectile and sexual functioning. This will help anyone (i.e., physicians and patients) understanding how to start with the prevention of damage and the subsequent EF recovery, thus reducing the plausible false expectations and subsequent frustrations.
Most of the historical data refer to open RP; overall, the incidence of post-RP ED varies between 14% and 90%. As a whole, the incidence of reported postoperative ED is extremely discrepant among series, because of a great variation in the nature of the populations studied and the modality for data collection and reporting; the great inconsistency in the definition of what is considered a normal EF before surgery and what one may consider a normal erection after RP emerged as the key problem in almost all these studies. The results of the meta-analysis conducted by Tal et al. clearly stated that most of the published literature does not meet strict criteria for reporting post-EF recovery. The same meta-analysis found as many as 22 different definitions of favorable EF outcome. In this context, the overall fixed effects EF recovery rate was 58% (95% CI: 56–60%), with significant heterogeneity among effect impacts. Similar results were also discussed by Burnett et al. as a side analysis of outcomes assessed as part of an update of the American Urological Association (AUA) PCa guidelines. They reported how, in many instances, only qualitative and subjective determinations were used, thus interpretable at best as erectile ability insufficient, somewhat functional, or regularly sufficient for sexual intercourse. Moreover, it has been well-observed that EF data from the largest series often refer only to a small fraction of the total RP population since the evaluable number of patients often had represented only a fraction of the total exposed to surgery. Therefore, these are some of the most significant obstacles to the accurate interpretation of the incidence and prevalence of post-RP ED, mainly when considering all study types and all technical approaches available.
Laparoscopic and, even more, many large series of robotic-assisted approaches are mature enough and have demonstrated that EF outcomes are at least equivalent to those obtained with open RP. Still, a number of limitations for a correct and objective interpretation of results are also discernible in the literature that deals with this type of surgery.
The literature clearly highlights that preoperative EF is an important predictor of EF recovery after RP. To this specific purpose, it is mandatory to verify how the definition of baseline EF was done; indeed, numerous assessment modalities have been reported in the literature, thus including patients subjective self-reports, partner-corroborated function and validated psychometric instruments. Overall, we consider of critical importance the analysis made by Mulhall, who reported that a clear mention of baseline EF was only given in only 16 (66%) of 24 studies considered as representative of the experience of large volume worldwide centers. In this context, it was a further recommendation of the ICSM committee that clinicians should use a validated psychometric instrument, with recognized cut-offs for normalcy and severity, during the pre and postoperative evaluation of their patients. Either the International Index of Erectile Function (IIEF) or the Sexual Health Inventory for Men (SHIM)—with cut-off scores for 'normal' EF of 26 and 21, respectively—keep their clinical usefulness to define EF.
Baseline EF assessment is still problematic and the most reliable timing of this assessment is even more poorly defined: on the one hand, some patients might overestimate their previous EF; on the other hand, proximity to the surgery may reduce the sexual activity/desire of either the patient, his partner or the couple as a whole. PCa diagnosis, cancer-related or treatment-associated psychological distress may also significantly impair the real-time assessment of EF immediately prior to RP; therefore, this "late" real-time evaluation might not be fully representative of the patient's true sexual functioning. Kim et al., for instance, reported that in order to accurately assess the pre-diagnostic baseline EF in candidates for RP, the psychometric tools should be administered before prostate biopsy rather than before robot-assisted laparoscopic radical prostatectomy (RARP) since cancer diagnosis-related symptoms and depression can ultimately affect sexual function and index scores.
Overall, the definition of ED of the National Institutes of Health (NIH) was not designed to be applied to a specific population, and even less for a complex population such as the patients undergoing RP; this is of particular importance today because such a widely-used definition does not include any mention of the role or use of erectogenic aids or other assistance, which are hugely suggested in PCa patients after surgery. Adequate knowledge of the potential use of any preoperative or post-RP erectogenic aid and what proportion of data in any given series was collected from patients using these agents are of relevant importance to allow an accurate interpretation of the findings. These further aspects make giving a proper definition of postoperative EF extremely difficult.
A further crucial aspect is the definition of what the patient can actually expect after surgery, that is the concept of regaining EF "back to baseline"; indeed, a significantly small proportion of preoperative potent men may spontaneously return to baseline EF after RP. Having in mind the clear intention of limiting patient false expectations, clinicians have to comprehensively discuss the objective of regaining an erection equivalent to that prior to RP, especially using data from their own RP population. If we start from the NIH definition of ED, the focal point would become the fact that adequate postoperative erections may be "at least" sufficient for satisfactory sexual performance. Mulhall reported that adequate EF was defined as the "ability to have successful intercourse by patient self-report" in 42% out of the series taking into consideration in his own meta-analysis. Unfortunately, overall 37% of the series did not even report how the authors define adequate erections. More recently, Nelson et al. considered 24-mo follow-up data from 180 men submitted to RP; of them, when including men who were using a PDE5I at 24 months, 43% got back to their baseline EF, while 22% of the whole cohort returned to the baseline EF without the use of any PDE5I. For this group, there was a significant difference by age, which remained a significant predictor (OR =6.25, P<0.001) at multivariable analysis.
In an attempt to combine the two concepts of getting EF "back to baseline" and being able to achieve erections sufficient for satisfactory sexual intercourses, as originally suggested by the NIH, it becomes important to consider the potential misinterpretation of the established cutoffs for normalcy as well as the grading of ED severity (mild, moderate and severe) of both the IIEF-EF domain and SHIM. Indeed, using the usual cutoffs for normal function—which are generally considered for the broad-spectrum ED population—might be overly stringent for post-RP populations; indeed, there are patients that still consider themselves to be fully functional while having lower scores. In order to try and define a cut-off value as close as possible to the real-life setting, Briganti et al. considered a relatively small cohort of preoperatively fully potent patients (IIEF-EF ≥26) treated with retropubic BNSRP at a single institution and suggested that a cut-off of IIEF-EF ≥22 may represent a reliable score for defining EF recovery after BNSRP.
Another crucial aspect that has to be discussed with the patient is the issue of the chronology of events of recovery and the post-operation period. Burnett et al. rightly commented that in the modern era of RP the majority of men usually achieve resumption of all physical activities, recovery of urinary control and normalization of bowel function within a few months after surgery. In contrast, postoperative EF continues to improve over time, at least up to 24 months and in some series up to 48 months post-RP. Overall, although the data are not entirely unambiguous, RARP seems to promote a faster EF recovery as compared to open RP.
Time of erection recovery does not uniformly occur in all cases and a number of predictors of EF recovery have been identified, including patients' age at surgery (i.e., the younger the better), better preoperative EF, extent of neurovascular bundle preservation and erectile hemodynamic changes after surgery. In this context, surgery (i.e., type, quality, surgical volume and the actual NS approach) probably emerges as the most compelling aspect. In this context, Tal et al. reported that BNSRP was certainly associated with higher EF recovery (P=0.01) as compared with UNSRP. When dealing with preservation of the neurovascular bundles (NVB), most patients—and, unfortunately, a number of clinicians—do not have an adequate understanding of the concept of NS; indeed, they think that NS always leads to complete preservation of the nerves and, consequently, to the absence of any transient postoperative ED. This is not correct; even when surgeons believe that they have achieved complete BNS, there is inevitably some trauma to the nerves so, in order to prevent false and unrealistic expectations, clinicians have to provide patients with a realistic time frame for EF recovery. Experts suggest that a potential period of 6–36 months would be necessary, although most men have a functional recovery within 12 and 24 months since RP. Katz et al. showed that the recovery of functional erections in the early postoperative phase, especially without the need for PDE5Is, is a good prognostic indicator for EF at 12-mo assessment. Thus, it should be stated with the patients that the ability to have either a spontaneous or a pharmacologically-assisted functional erection (namely PDE5I-sustained) within three months of RP is an excellent prognostic indicator. No less important, the fact that it can take a long time until the first spontaneous erections occurs should not lead the physician to wait inactively: indeed, the patient should start with supportive medication therapy for EF recovery as early as possible.
As a further major aspect, the clinician should also debate issues concerning the quality of erection. In this context, one of the parameters which have to be taken into account is the hardness of erection, mostly defined using a 4-point scale such as the Erectile Hardness Score (EHS). Indeed, although a patient may postoperatively have functional erections, which allow him to have sexual intercourse, a more or less severe loss of erection hardness may lead to erection dissatisfaction for the same man. Consequently, he might deserve erectogenic compounds for greater erection hardness, or even a second or third line treatment, if that gentleman was already using an erectogenic medication. A second parameter is the consistency of functional erections, which means how consistently a functional erection can be obtained. Data regarding RP populations are still lacking.
Prevention and management of EF in patients treated with RP is necessarily heavily predicated upon a careful choice of the correct patient for the correct type of surgery: clinicians should comprehensively discuss the recognized predictors of EF recovery with any candidate for RP, and all patients with PCa who might benefit from RP as a curative treatment should also receive an appropriate counseling regarding (I) the possibility of being subjected to a RP [see, in this context, the most updated EAU guidelines]; and, (II) the possibility of being subjected to a NSRP or, conversely, the need to be treated with NNSRP, according to the baseline oncological condition. Imbimbo et al. investigated factors related to patients' desire to preserve post-RP sexual activity and those determinants for surgeons' final decision to eventually perform a NSRP. Overall, 69% of the patients were preoperatively interested in preserving their sexual activity. Of the entire cohort, 13% were not interested but suitable for a BNSRP, 18% were neither interested nor suitable, 39% were both interested and suitable, but up to 31% were interested but not suitable. Age and normal preoperative sexual function parameters emerged as independent determinants of patients' desire to preserve postoperative sexual functioning. Overall, 13% underwent an UNSRP and 36% a BNSRP. Along with oncological indications, age and patients' desire to preserve sexual activity were among the main independent determinants of surgeon's final decision for a NSRP. Overall, findings from this study underlined the existence of discrepancies among patient's desire to preserve postoperative sexual function, guideline indications to NSRP, and surgeons' final decision for a NS approach.
Therefore, once established that the patient can eventually receive a NSRP, counseling should focus on the patient's baseline functional situation along with the potential predictors of post-operative EF recovery. Preoperatively, these factors necessarily include age at surgery, baseline EF, body mass index and comorbidities. Likewise, type of surgery, coupled with surgical volume and surgical skill, and NS status achieve the role of significant contributors to EF recovery. Briganti et al. developed a preoperative risk stratification tool aimed at assessing the probability of EF recovery after open BNSRP. They used routinely-available baseline data, such as patient age and preoperative EF, as psychometrically objectified with the IIEF; moreover, as a proxy for general health status, the authors scored health-significant comorbidities using the Charlson Comorbidity Index (CCI). For the specific purpose of the analysis, CCI was categorized as a score of 0, 1, or ≥2. The resulting tool was able to stratify patients into three groups according to the relative preoperative risk of post-RP ED: low (age ≤65 years, IIEF-EF ≥26, CCI ≤1), intermediate (age 66–69 years or IIEF-EF 11–25, CCI ≤1), and high risk (age ≥70 years or IIEF-EF ≤10 or CCI ≥2). More recently, Novara et al. applied the same risk stratification categories to a relatively small cohort of patients treated with BNS RARP who were assessed at a minimum 12-mo follow-up; according to the risk-group stratification proposed by Briganti et al., the 12-mo EF recovery rate was 82%, 57% and 29% in the low-risk, in the intermediate-risk, and in the high-risk group, respectively (P<0.001).
Overall, prevention and management of postoperative EF necessarily pass through rigorous selection of the patients who may benefit from RP: the clinician must clearly inform the patients that the NS approach does not invariably ensure the recovery of erections at all; moreover, since this type of surgery may be potentially subjected to a number of sequelae, a NS approach should be reserved for young patients without significant comorbidities and an adequate preoperative EF.