The effect of the discrepancy between pre- and post-operative staging on decision-making and quality of life in men undergoing a radical prostatectomy

1. Introduction

Prostate cancer (PCa) is the most prevalent cancer and the second leading cause of cancer mortality in men [1]. Prostate tumours are the fourth most common tumour worldwide with an estimated 1,414,259 (7.3%) new cases in 2020 [2]. In Spain, PCa is the second most frequent cancer [3] and it accounts for 12.9% of newly diagnosed cases [4]. The northwest and southwest are areas with high mortality from PCa compared to the rest of the country [5].

PCa incidence data vary considerably throughout the world [6]. This may be explained by the use of Prostate-Specific Antigen (PSA) as a screening method [7]. However, a clear geographical predominance has been observed in regions of African-American ethnicity [8]. Therefore, some authors question whether this great difference between areas is due to screening alone [9].

Age is the main risk factor for PCa [6]. A study in the USA linked the incidence of PCa with advanced age, African ethnicity and family history [10]. The importance of androgens in its aetiopathogenesis has also been widely reported [11]. However, only one prospective research study measuring serum testosterone in relation to the occurrence of PCa showed a statistically significant increase in risk [12]. Men with hypogonadism had a lower risk of PCa [13], while treatment with exogenous testosterone is not associated with an increased risk [14]. Currently, no clear relationship has been found between serum testosterone levels and the appearance of PCa [15].

PCa staging allows for an estimation of prognosis and is involved in therapeutic decision-making [16]. Pre-surgical clinical staging is based on a digital rectal examination [17], PSA [18] and the transrectal biopsy Gleason score [19]. The post-surgical pathological stage is based on the analysis of the surgical specimen [20]. Magnetic resonance (MRI) is the most accurate imaging test to assess the PCa stage, modifying the initial surgical template in 35% of cases [17]. However, MRI is not widely used when deciding which surgical approach should be followed [20]. Aside from being traditionally used to guide repeated biopsies in order to improve the detection of clinically relevant PCa and the accuracy of the Gleason score, the multiparametric-MRI has also emerged as a tool to determine clinical tumour aggressiveness [17].

A radical prostatectomy (RP) is recommended when aiming to cure resectable disease, which often affects patients’ quality of life [21]. It can have physical consequences such as male sexual dysfunction (MSD) [22, 23], urinary incontinence [24, 25], and future bowel disturbances, including recurrent subocclusive symptoms [26]. MSD includes hypoactive desire disorder [27], erectile dysfunction [28], and orgasm [23] and ejaculation disorders [29]. MSD has a great impact on quality of life [30, 31] with erectile dysfunction being of greatest concern [32]. Other psychological and emotional alterations related to the disease have also been described [33], such as the effect on self-esteem [34], irritability or fear [35]. In addition, the distress felt by men undergoing RP also contributes to the suffering of their family members, who play a key role in caregiving and emotional support [36]. The patients undergoing RP also experience significant repercussions on their social lives and on their relationships with their families and partners [37]. The psychosocial implications of the disease and the decision-making process for its treatment are very expensive for the system [38], which is why some authors advocate including psychosocial costs in the financial evaluations of healthcare systems [39].

Several studies report clinical understaging of the disease when compared to the pathological staging obtained after RP. Thirty percent of patients with a Gleason score of 6 in preoperative biopsy specimens have a higher Gleason score after surgery. In those with a Gleason score of 7 or higher, this increases to 34.5% of cases [40]. The therapeutic management of PCa has serious repercussions on both the sexual [21] and socio-familial spheres [37]. Therefore, clinicians require tools to be able to determine the final pathological stage accurately. According to some authors, this continues to be a challenge in routine clinical practice [41]. For this reason, we consider it advisable to carry out a study that compares pre-PR and post-PR variables, and analyze their behaviour to ensure correct decision-making prior to choosing the targeted treatment. The aim of this study is to describe and analyze the relationship between sociodemographic factors, quality-of-life and clinical variables in patients undergoing a radical prostatectomy.

2. Materials and methods

3. Results

4. Discussion

Several authors highlight the impact of prostate surgery on quality of life [42, 43]. It is therefore becoming more common to opt for an initial conservative treatment after being diagnosed with the disease [44]. Delaying or avoiding surgical treatment, together with active surveillance measures, may improve quality of life [45] and thus be an alternative to a radical prostatectomy. However, some authors question the effectiveness of this active surveillance practice in relation to survival [46].

The diagnostic algorithm of a PCa patient is based on physical examination, imaging tests and pathology. For years, tools have been sought to predict pathological staging at diagnosis [41]. The usefulness of PSA and the Gleason score has been widely validated as pre-treatment prognostic markers [19]. In addition to these factors, other authors have highlighted how positive surgical margins after RP are in predicting the risk of biochemical recurrence and estimate oncological targets [47]. Although clinical staging has been found to be a good independent estimator of disease progression, there is a tendency to underestimate the final pathological stage at diagnosis [41]. This is consistent with our data, where this occurs in up to 75% of cases.

Digital rectal examinations are among the diagnostic modalities for the detection of PCa. However, they are currently in disuse according to Borkenhagen et al. [48]. For Yamamoto et al. [49] it is a useful tool in the estimation of prostate volume, although Boesen [17] indicates that it has a number of limitations. This author highlights the limitation of digital rectal examinations given that most tumours are not palpable until they reach a certain size. Among our participants, only 37.5% had a concerning digital rectal examination at diagnosis. This contrasts with the 55% of cases diagnosed by digital rectal examination described in another study [18]. Although these figures are not very encouraging to support its use as a screening method, Okotie et al. [50] highlights that it is a tool that diagnoses up to 18% of PCa with normal PSA levels. It should also be noted that RT remains an indispensable tool in the diagnosis of PCa as undifferentiated tumours may tend not to raise PSA levels. Therefore, basing the diagnosis of suspected PCa on PSA alone can be misleading. In addition, in the case of benign prostatic hyperplasia, size assessment can guide the selection of different treatments among those currently available.

Significant differences were found between the Gleason score obtained from the biopsy and that from the surgical specimen. Tumour aggressiveness was underestimated in over 40% of cases. The less aggressive the tumour appeared on a transrectal biopsy, the more it was underestimated. To improve the use of the Gleason score, Heidegger et al. [51] recommend the International Society of Urological Pathology (ISUP) modified Gleason score as a marker that may be beneficial in risk estimation. However, for Novak et al. [52], the preoperative usefulness of the ISUP in predicting pathological features of the RP sample is controversial, as observed in our results. According to Ikeda et al. [53], the Gleason score is an independent prognostic tool, so an adequate interpretation and estimation of the final Gleason score is crucial when managing patients with PCa.

When measuring prostate volume, the sensitivity and specificity of ultrasound-guided biopsy has been described as low/moderate, as there is a significant probability of not biopsying the tumour area or not picking up the most aggressive areas of the tumour [54]. This is consistent with the results of our study in terms of prostate volume, as there was a significant difference between the volume of the ultrasound image and the final volume of the surgical specimen. However, other studies have found that it is possible to stratify prostate volume with high accuracy by digital rectal examination into >30 mL and <30 mL groups [49]. Therefore, since the gold standard for the diagnosis of this pathology includes an anatomopathological study, the use of MRI is being implemented to guide the biopsy [55], which improves anatomical determinations, lesion characterization and the use of biopsies in appropriate areas.

Being overweight or obese was related to greater tumour aggressiveness according to the Gleason score. There are significant differences in Gleason scores between healthy weight and overweight or obese patients [56]. This is consistent with our results, which demonstrate that patients with higher aggressiveness on the Gleason score have a BMI 3.39 higher than participants with lower aggressiveness on the Gleason score. However, as our study is not designed to identify causal factors, we cannot make any conclusions of our own in this regard. This has also been supported by other authors, in that obesity has been associated with advanced PCa with stage T3 or Gleason ≥7 [57]. Given our study’s design and sample size, causal inference is not possible. The pathophysiological mechanism that demonstrates how obesity plays a role in the aggressiveness of the disease, has been explained by adipocyte-generated mediators [58].

Patients with greater tumour aggressiveness were less concerned with the sexual aspects of the disease and focused their attention on the purely clinical side. This could be explained by how the disease process is involved in the different spheres of quality of life [59, 60]. Taking the clinical diagnosis as a reference for therapeutic decision-making can lead to a reduction in quality of life [21]. RP can lead to the appearance of sexual dysfunction [61, 62], urinary incontinence or anastomotic stenosis [63]. However, the appearance of sexual dysfunction will also depend on the baseline situation of the patient [64]. Although previous evidence suggests that age is related to a higher occurrence of erectile dysfunction [23], our results suggest that a lower percentage of older adults seek medical consultation for this reason. Changes in the sexual sphere are a key concern for patients undergoing RP [21]. In addition to these organic adverse effects, other psychological and emotional chages related to the disease have been described [33]. The social, family and partner context also has a considerable impact on patients undergoing RP [37]. Despite this, measures taken by the health and social care systems are generally focused solely on the patient and not so much on those at their side [23].

The main limitation of the present study is the sample size. Difficulties were encountered in data collection due to the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov2) pandemic. Access to the hospital for research purposes was limited at the time the data collection was planned to take place, as priority was given to entry for clinical purposes. Given the sample size and the retrospective, cohort design of the study, it is difficult to draw conclusions that can be extrapolated to the general population. In the hospital where the data were collected, the IIEF questionnaire was administered only once prior to surgery. In order to overcome this limitation, clinical histories were reviewed in order to compile information on whether the patients had sought consultation for erectile dysfunction.

5. Conclusions

Pre-surgical clinical staging determines the decision of how to treat prostate cancer. A radical prostatectomy may have implications for quality of life. Therefore, knowing if there is a correlation between clinical and pathological staging is considered necessary to provide individualized treatment. Our results suggest that older age could be related to increased erectile dysfunction, that obesity could be related to more aggressive prostate cancer, and that there can be differences in the Gleason score between the biopsy and the final specimen. No differences were found between clinical and pathological staging. However, we should consider whether their correlation is sufficiently robust for clinical staging to be used for both therapeutic management of the patient and for joint decision-making. These findings suggest that the Gleason score results should be interpreted cautiously.

Future research with a larger sample size is required to corroborate whether the Gleason score and the pre-surgical clinical stage concurs with post-surgical information. Further research about the influence of body mass index on the pathogenesis of prostate cancer should be addressed. Both elements need to be taken into account when making decisions about the therapeutic management of PCa. Moreover, research on the influence of prognosis on the psycho-emotional state of the patient and their environment would be desirable.

Abbreviations

PCa, Prostate Cancer; RP, Radical Prostatectomy; MSD, Male Sexual Dysfunction.

Availability of data and materials

The data presented in this study are available on reasonable request from the corresponding author.

Author contributions

TFA, ÁMB, CFS and JMHP—designed the research study. ÁMB, APPM, GGH and TFA—performed the research. CFS, APPM, IDS and GGH—provided help and advice on critical review of the manuscript. ÁMB, JMHP, IDS and TFA—analyzed the data. JMHP and ÁMB—wrote the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The study was approved by the “Comisión de Evaluación de Trabajos de Investigación” (Research Works Evaluation Commission) of the Hospital General Universitario Morales Meseguer, Murcia, Spain with code CETI: 13/21. The patients provided informed consent and agreed to publication of the details of this research.

Acknowledgment

The authors would like to express their gratitude to Isi Soliani for his linguistic services, and to the CTS-451 Health Sciences Research Group, belonging to the CEINSA (Health Research Center) of the University of Almería.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

Supplementary material associated with this article can be found, in the online version, at https://oss.jomh.org/files/article/1685891518229823488/attachment/Supplementary%20material.docx.