Epidemiologic profile and prognostic factors in clinically localized prostate adenocarcinoma submitted to surgical treatment

Abstracts

OBJECTIVE: Radical prostatectomy remains the standard treatment for early prostate cancer. This study was conducted to evaluate the outcome and prognostic factors of radical prostatectomy. METHODS: A total of 500 patients with prostate cancer underwent radical prostatectomy at Santa Rita hospital- Maringa-PR, between 2000 and 2006. Clinical staging, preoperative prostate-specific antigen (PSA) and Gleason score were evaluated with pathological stage and margin status. Follow-up PSA monitoring and survival were analyzed. RESULTS: Of 500 patients with clinical localized disease with a median follow up of 36,7±18,8 months. The average operative duration was 190± 45 minutes and the average intra-operative bleeding was 630 ml. The patients' preoperative serum PSA was 7,8 ± 4,5 ng/dl , with a higher proportion of Gleason Score < 6(72%) and The TNM stage pT2c (65%). For late postoperative complications: incontinence in 2% and 46 % with erectile dysfunction. CONCLUSION: Radical prostatectomy in men shows excellent results. The chance of recurrence was directly associated with PSA = 10 ng/ml, high Gleason score and inversely proportional to age.

Prostatic neoplasms; Prostatic neoplasms; Prognosis; Adenocarcinoma; Prostatectomy

OBJETIVO: Avaliar a evolução e os fatores prognósticos da prostatectomia radical. MÉTODOS: Um total de 500 pacientes foi submetido à prostatectomia radical, entre 2000 e 2006. Estádio clínico, PSA pré-operatório e escore de Gleason foram avaliados em conjunto com o estádio patológico e margens cirúrgicas. O seguimento foi feito pela monitorização do PSA e correlação com diversos critérios. RESULTADOS: Dos 500 pacientes com doença clinicamente localizada tiveram seguimento médio de 36,7 ± 18,8 meses. O tempo operatório foi de 190 ± 45 minutos e o sangramento intra-operatório de 630 mL. O PSA pré-operatório médio foi de 7,8 ± 4,5 ng/dL, com maior proporção de escore de Gleason<6 (72%) e estádio TNM pT2c (65%). As complicações pós-operatórias foram incontinência em 2% pacientes e 46% com impotência sexual. CONCLUSÃO: A chance de recorrência esteve diretamente associada com PSA=10 ng/mL, escores de Gleason maiores e inversamente proporcionais à idade dos pacientes.

Neoplasias da próstata; Neoplasias da Próstata/cirurgia; Prognóstico; Adenocarcinoma; Prostatectomia

ORIGINAL ARTICLES

Epidemiologic profile and prognostic factors in clinically localized prostate adenocarcinoma submitted to surgical treatment

Aissar Eduardo Nassif, ACBC-PR^I; Renato Tâmbara Filho^II; Regina Xavier Gomes de Paula^III; Willian Setsumi Taguchi^IV; Helio Jorge Pozzobon^V

^IDoctoral student, Graduate Program in Clinical Surgery, Universidade Federal do Paraná and Associate Professor, Universidade Ingá (UNINGA), Maringá, PR, Brazil

^IIPhD, Associate Professor of Urology, Universidade Federal do Paraná, Curitiba, PR, Brazil

^IIIPhD, Professor, Universidade Positivo, Curitiba, PR, Brazil

^IVPhD, Associate Professor, Universidade Estadual de Maringá (UEM), Maringá, PR, Brazil

^VHead, Urology Service, Hospital Santa Rita, Maringá, PR, Brazil

Correspondence address

ABSTRACT

OBJETIVE: Radical prostatectomy remains the standard treatment for early prostate cancer. This study was conducted to evaluate the outcome and prognostic factors of radical prostatectomy.

METHODS: 500 patients with prostate cancer underwent radical prostatectomy at the Hospital Santa Rita, Maringá, PR, Brazil, between 2000 and 2006. Clinical staging, preoperative prostate-specific antigen (PSA) and Gleason score were evaluated in conjunction with the pathological staging and margin status. Follow-up PSA screening and survival were analyzed.

RESULTS: The mean follow-up for the 500 patients with clinically localized disease was 36.7±18.8 months. Average operative time was 190± 45 minutes and average intraoperative blood loss was 630 mL. Mean preoperative serum PSA was 7.8 ± 4.5 ng/dL, with a higher proportion of Gleason Score<6 (72%) and TNM stage pT2c (65%). Late postoperative complications: incontinence in 2% and erectile dysfunction in 46% of the patients.

CONCLUSION: Radical prostatectomy shows excellent results. The likelihood of recurrence was directly correlated with PSA = 10 ng/mL and a high Gleason score, and inversely correlated with age.

Key words: Prostatic neoplasms. Prostatic neoplasms/surgery. Prognosis. Adenocarcinoma/epidemiology. Prostatectomy.

INTRODUCTION

Prostate cancer is the most frequent visceral malignancy in men, with the exception of skin tumors, and incidence tends to escalate over the next decades with the increase in life expectancy^1-3. The risk of developing the disease over a lifetime is 17.6% for white men and 20.6% for black men^4-6. Approximately 543,000 new cases are diagnosed worldwide each year⁷. In the United States, 234,460 cases were diagnosed in 2006 with 27,350 deaths, which makes it the second malignancy in number of deaths of men⁷.

Prostate cancer, at its early stages, is a curable disease through surgical procedures, radiotherapy and other methods³. In select cases, clinical surveillance may be a choice^1,8. Possible late recurrences are suggestive of understaging or a tendency to early metastasis². Given these facts and the high incidence of this disease, endeavors are justified in the search for the enhancement of early detection methods and prognostic markers, with the resulting improvement in therapeutic planning ^{6, 9, 10}.

Despite the expansion of knowledge on the epidemiologic and biomolecular aspects of prostate cancer, it cannot be predicted which patients will develop clinically significant disease and which will remain with an organ-confined tumor^11-13.

The objective of this study was to analyze the epidemiologic data and evaluate the prognostic factors of the patients with clinically localized prostate adenocarcinoma who underwent surgery at the Uro-Oncology Service of the Hospital Santa Rita, Maringá, PR, Brazil.

METHODS

This study was approved by the Human Research Ethics Committee of the Hospital de Clínicas of the Universidade Federal do Paraná. The study involved 500 cases of prostate neoplasia patients from private practice (Clínica Urológica de Maringá) submitted to radical prostatectomy and pelvic lymphadenectomy in the period from January 2000 through December 2006. Initially, the study was undertaken through a review of medical records, after which the patients were evaluated through self-administered questionnaires (IIEF-5 – International Index of Erectile Function, and IIQ – Incontinence Impact Questionnaire) and interviews. All anatomopathological reports came from the same laboratory and were reviewed by two pathologists.

All patients had been diagnosed with prostate adenocarcinoma, the usual acinar pattern, with clinical preoperative staging between T1c and T2c. The clinical history, general and urological examinations, lab tests (complete blood panel and specific testing for prostate-specific antigen, PSA), epidemiologic data, operative time and blood loss were systematically analyzed by the same investigator.

Transrectal ultrasound evaluation and biopsy were performed by the same professional. The transrectal ultrasound-guided biopsy was carried out by an extended protocol with sampling from lateral regions and from the transition zone, with 12 or 14 specimens. The patients underwent preoperative staging tests with bone scintigraphy, chest radiographs and pelvic CT scans or magnetic resonance imaging, as needed.

The patients were staged in accordance with the latest update issued by the International Union Against Cancer (UICC) using the TNM classification. After confirmation of diagnosis by biopsy, there was a four- to six-week wait before surgical treatment.

All patients were followed-up every four months during the first two years and every six months from the third to the fifth year. Those reviews included clinical examination, urological examination (digital rectal exam) and blood biochemistry (hemogram, creatinine, alkaline phosphatase and PSA). After the fifth year, the patients were counseled to do only the PSA testing once yearly. Radiological evaluation was only conducted on patients who showed biochemical recurrence or measurable tumor progression. The recurrence criterion was the elevation of PSA to levels =0.2 ng/mL.

For statistical analysis, Student's t parametric test and the nonparametric Mann-Whitney test were used, as well as the comparison between two proportions (through the Primer of Biostatistics software), chi-square and Fisher's Exact test (by Epi-Info). The level of significance was set to 5% (P<0.05).

RESULTS

Mean operative time was 190 ± 45 minutes and mean blood loss was 630 mL. Follow-up ranged from 16.7 to 108 months, with a mean of 36.7 ± 18.8 months. Mean age was 63.7 ± 6.8 years, ranging from 44 to 75 years, with a higher number of subjects in the sixth decade (58.0%) (Table 1).

Preoperative PSA was 7.8 ± 4.5 ng/dL (median = 6.5), ranging from 2.3 to 24.0 ng/dL. Most patients (70.0%) had PSA ranging between 4.0 and 9.9 ng/dL. A greater proportion of Gleason scores up to 6 (72.0%) was found, and the predominant pathological staging was pT2c (65.0%).

Of all the patients operated on, 98% remained continent (87.0% without pads, 11% using up to one diaper/day). With regard to sexual potency, 54% remained potent, and of these, 5% remained so without using any aid, and 49.0% were potent using phosphodiesterase inhibitors and/or penile injections; 46.0% became impotent, 12% of whom refrained from using any method.

Intraoperative complications were rectal injury (0.6%) and vascular injury (0.2%). Postoperative complications were acute myocardial infarction in the immediate postoperative period followed by death (3 cases = 0.6%), bladder neck contracture (0.8%), urethral stenosis (2.4%), acute urinary retention (1%), lymphocele (0.6%), recto-vesical fistula (0.2%), surgical wound infection (5.6%) and incisional hernia (0.8%).

In the assessment of PSA evolution (PSA control), a significant difference was found only in PSA, indicating that the patients with recurrence showed a higher proportion of PSA =10 ng/dL (P=0.023). When comparing the PSA groups (Cure vs Recurrence), the following significant differences were found for the group of patients with recurrence: patients were younger, 2.1 years on average (P=0.024); belonged to the group with higher PSA levels (P=0.002); with a higher Gleason score (P=0.006); and longer follow-up (P=0.025) (Table 2).

DISCUSSION

The chief purposes of staging prostate cancer are to predict prognosis and to assist in the choice of therapy. Staging is primarily based on the extent of the disease and on what can be established when correlated with the nomograms. Staging, PSA and Gleason score are the key parameters ^14-16.

The anatomic extent of the tumor is the most important and most widespread prognostic factor. The TNM classification is internationally adopted to describe and compare disease presentation patterns as well as the impact of screening and access to treatment, creating a universal language and affording standardized indication of treatment^17,18.

PSA is a tissue marker, however not tumor-specific. It is a low molecular weight glycoprotein (33 kDa) of the kallikrein family that is excreted by the prostatic ducts into the urethral lumen as part of the seminal plasma. Its levels of sensitivity and specificity preclude utilization as a stand-alone method . There was a great increase in the number of diagnosed tumors that were well- or moderately differentiated, nonpalpable on digital rectal exam. Screening through PSA made possible earlier diagnosis, hence a higher cure rate, and even allowed to put patients under clinical surveillance ^8,19.

Additionally, PSA testing is useful in treatment monitoring, since if PSA levels do not decrease to an undetectable level after radical prostatectomy, or even increase – especially during the first year –, that is suggestive of distant metastasis²⁰. For many patients, detectable PSA levels after radical prostatectomy are associated with disease recurrence, and the mean time interval between PSA recurrence and death from cancer lies somewhere between 5 and 12 years, depending on the Gleason score⁹.

This score correlates with the extension of the disease, particularly with the risk of extraprostatic extension, acquiring an independent prognostic value²¹. Tumors with a Gleason score =7 are considered to be biologically aggressive, those with a score of 5 or 6 are tumors showing intermediate aggressiveness, and those between 2 and 4 are less biologically aggressive²². Grading in the Gleason system – which is the most widely used today – is based on glandular differentiation and on the growth pattern in relation to the stroma^21,23. In this system, nuclear atypia are not taken into account; in fact, to date, the evaluation of cell nuclei has not been shown to be superior to glandular pattern assessment in prostate adenocarcinoma^24,25. According to this system, histologic grade can range from 1 to 5 and the final sum will range from 2 to 10. A pattern of Gleason 4 or 5 is virtually predictive of a worse course^6,26,27. Contrary to the other systems, both the predominant pattern and the secondary pattern are factored in²¹. The Gleason score is more reliable in radical prostatectomy or endoscopic resection specimens than on needle biopsy specimens, as understaging is frequent in the latter^{11, 28}.

The results found herein concerning age, PSA, Gleason score, clinical and pathological staging and complications were in agreement with data from the literature^10,14,28-31. Tumor recurrence was directly correlated with PSA=10 ng/mL and a higher Gleason score, and inversely correlated with age.

Regarding postoperative quality of life, the data gathered in the present study are in line with those from the literature, where the impotence rates reported are discrepant and high, varying between 60 and 90%^{17,18, 32}. Thompson et al. noted that younger men (<60 years) were more likely to maintain erections than older men, and that sexual health recovery continues beyond the first year and extends as long as to the fourth year, a fact that was observed in the present study, yet without statistical significance¹⁷. Alibhai and Klein et al. remarked that the rates of postoperative potency and continence are directly correlated with the surgeon's experience and hospital surgical volume ^{1, 33}.

In the same way as erectile dysfunction is directly associated with the surgeon's experience, so are genitourinary complications, urinary incontinence being the most relevant one^3,34. In the present series, 98% of the patients who underwent the surgery were continent (87.0% with no use of pads, 11% using up to one diaper/day) and 2 % were considered to be incontinent (using more than one diaper/day). Thompson et al. reported that 3 to 74% of the patients submitted to radical prostatectomy present with urinary incontinence, mostly transient and improving within one year after the procedure^{17, 35,36}.

In conclusion, the chance of recurrence was directly correlated with PSA=10 ng/mL and higher Gleason scores, and inversely correlated with the age of the patients.

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Publication Dates

• Publication in this collection
  09 Nov 2009
• Date of issue
  Aug 2009

History

• Accepted
  19 Jan 2009
• Received
  2008