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Introduction
Prostate cancer is the most common non-cutaneous cancer in older men (> 70 years old), with an accumulative risk by 8.3% and a mortality of 4.27%. In México, the incidence of accumulative risk for prostate cancer is 41.6%1-3. Prostate cancer is the most common cause of mortality from malignant tumors with an incidence of 16% in México. The most recent data published by the National Institute of Cancerology in México (INCan) indicate a mortality rate of 13 deaths per 100.000 men. In 2013, a mortality rate of six deaths was observed for every 100.000 men of 20 years old or more4. By the other hand, in the USA, the National Institute of Cancer (NIH) reports that at the time of diagnosis, 78% of cases are confined to the organ, with a relative survival of 100% to 5 years5.
Localized prostate cancer rarely causes symptoms; moreover, the presence of symptoms is frequent in locally advanced prostate cancer with a high growth rate or with metastatic disease6,7. The intervention of patients with localized prostate cancer should be made on time to provide a positive impact on the evolution of the disease; this approach could even be potentially curative2,6. Localized prostate cancer should be classified according to the risk group to develop recurrence of disease, using the D'Amico Classification8,9.
At present day, the radical prostatectomy is the only treatment for localized prostate cancer that shows benefits in global survival and specific cancer survivorship7. Different studies compare the radical prostatectomy with the conservative treatment (active surveillance); particularly, in a 15-year follow-up study SPCG-4 the authors founded a reduction of mortality (relative risk [RR] of 0.75). In another study, the radical prostatectomy was associated with a reduction in mortality of localized prostate cancer with a RR of 0.6210,11. In the 10-year follow-up study PIVOT, the subgroups analysis showed that in low-risk patients of prostate cancer, radical prostatectomy did not increase significantly the mortality by any cause (hazard ratio [HR]=1.15); At intermediate risk, radical prostatectomy reduced mortality of all causes (HR=0.69); in high-risk tumors, radical prostatectomy did not reduce significantly total mortality (HR=0.40)11-13. Another study for Gleason score >8, the biochemical progression-free survival at 5 and 10 years of follow-up ranges was between 35-61% and 24-39%, respectively, while the 5, 10, and 15-year specific cancer survival rate was 96%, 84-88%, and 66%, respectively2. In a cohort study on biochemical recurrence after radical prostatectomy stratification according to the risk classification of D'Amico, the accumulative incidence of biochemical recurrence of 10 years was 17.9%, 31.9%, and 47.9% for low, intermediate, and high-risk patients, respectively14.
High-risk localized prostate cancer is more likely to have early recurrence of prostate-specific antigen (PSA), with the need for secondary treatment, as well as a metastatic progression and death from prostate cancer. However, not all high-risk patients have bad prognostics after radical prostatectomy. The incidence of tumor limited to the organ is 26-31%15. The aim of the study was to evaluate the recurrence rate in patients with localized prostate cancer who underwent radical prostatectomy, according to the different risk groups in a third-level hospital.
Materials and Methods
Study design and settings
This was a observational, descriptive, comparative, and 5-year retrospective study of prevalence conducted in Bajio Regional High Specialty Hospital. The institution is a referral hospital, which provides tertiary care in the central region of Mexico.
Data collection
Data were collected from clinical records of patients with localized prostate cancer who underwent to radical prostatectomy in our institution. Patients were diagnosed with prostate cancer by transrectal biopsy or transurethral resection of the prostate, and then were referred to our hospital. The diagnosis of localized prostate cancer was made with extension studies, such as bone scintigraphy. Patients were evaluated with specific prostate antigen levels, digital rectal examination, and histopathological result. With this information, all patients were evaluated according to D'Amico classification. A radical prostatectomy was indicated and performed in these patients. In the follow-up, patients should remain stable without recurrence or persistence of the antigen. All clinical, surgical and pathological data were collected from medical records of the patients to analyze variables as sex, age, prostate biopsy, date of surgery, kind of surgery performed, transoperatory findings, pathology report, and PSA outcome.
Statistical analysis
For numerical variables, measures of central tendency and dispersion were calculated, and representative values were reported, according to the type of data distribution. For qualitative variables, proportions in percentage rates were determined. Contingency tables were constructed for independent and dependent variables. For qualitative variables, they were compared with the Chi-square test or Fisher's exact probability test, depending on the distribution of the expected values of the contingency table. For quantitative variables, the Student's t-tests were used to compare two non-correlated samples or their non-parametric equivalent if the data did not show normal distribution. The tests were performed considering a level of significance a=0.05
Ethics Committee Approval
This article was submitted for review by the Hospital's research and ethics committees, and after its approval it was executed. The agreements of the Declaration of Helsinki of the World Medical Association on ethical principles for medical research in human beings were followed. Each and every one of the data obtained was safeguarded; the identification data and any other personal data of the patient were not exposed.
Results
STUDY POPULATION
A total of 108 patients with prostate cancer undergoing radical prostatectomy were analyzed according to their risk group. Overall, the average age was 65.3 ± 5.91 years. About the comorbidities, diabetes mellitus occurred in 15.74%, hypertension in 29.63%, and other medical, surgical, and traumatic comorbidities in 55.56% of patients. The pathological diagnosis was made in 92.59% patients by transrectal prostate biopsy, while 7.4% were made by transurethral resection of the prostate (Table 1).
Tabla 1 General description of patients
| Variable | n (%) n=108 | |
|---|---|---|
| Age | 65.3 ± 5.91 | |
| Sex | ||
| Male | 108 (100%) | |
| Background | ||
| DM* | 17 (15.74%) | |
| AH** | 32 (29.63%) | |
| Other | 60 (55.56%) | |
| Pathological diagnosis performed by | ||
| Transrectal prostate biopsy | 100 (92.59%) | |
| Transurethral resection of prostate | 8 (7.41%) | |
| Gleason prior to surgery | ||
| 2+2 | 4 | 3 (2.78%) |
| 2+3 | 5 | 1 (0.93%) |
| 3+2 | 5 | 1 (0.93%) |
| 3+3 | 6 | 67 (62.04%) |
| 3+4 | 7 | 25 (23.15%) |
| 4+3 | 7 | 10 (9.26%) |
| 3+5 | 8 | 1 (0.93%) |
| Recurrence risk groups according to D'Amico | ||
| Low | 36 (33.33%) | |
| Intermediate | 60 (55.56%) | |
| High | 12 (11.11%) | |
| Surgical approach | ||
| Retropubic | 64 (59.26%) | |
| Retropubic + pelvic lymphadenectomy | 32 (29.63%) | |
| Laparoscopic | 12 (11.11%) | |
| Surgical bleeding | 842.03 ± 600.20 | |
| Gleason post-surgical | ||
| 3+2 | 5 | 1 (0.93%) |
| 3+3 | 6 | 53 (49.07%) |
| 3+4 | 7 | 30 (27.78%) |
| 4+3 | 7 | 12 (11.11%) |
| 4+4 | 8 | 7 (6.48%) |
| 3+5 | 8 | 1 (0.93%) |
| 5+3 | 8 | 0 (0%) |
| 4+5 | 9 | 2 (1.85%) |
| 5+4 | 9 | 1 (0.93%) |
| 5+5 | 10 | 1 (0.93%) |
*DM: Diabetes mellitus,
**AH: Arterial hypertension.
Risk classification analysis
Regarding the classification of the risk of recurrence according to the D'Amico scale, the following was observed: thirty-six patients (33.33%) presented low risk, 60 patients (55.56%) presented intermediate risk, and 12 patients (11.11%) were identified as high risk. According to surgical management, open retropubic radical prostatectomies were performed in 64 patients (59.26%) of these 40 patients with intermediate risk, no pelvic lymphadenectomy was performed due to the calculated probability of lymph node involvement <5%, high-risk patients underwent pelvic lymphadenectomy, in another group of patients open retropubic prostatectomy plus pelvic lymphadenectomy were performed in 32 patients (29.63%), and laparoscopic radical prostatectomy in 12 patients (11.11%) who were classified as low risk. The average bleeding was 842.03 ± 600.20 ml. One death from acute myocardial infarction was identified 15 days after surgery. These and other descriptive patient data are shown in detail
Surgical piece analysis
In the surgical piece analysis, 28 patients (25.93%) were found to have adverse characteristics; six patients (50%) corresponded to the high-risk group, 17 patients (28.33%) to the intermediate group, and five patients (13.89%) to the low-risk group.
Persistence of PSA
In the clinical course of patients with PSA control, found out that nine (8.33%) patients presented persistence of PSA; four patients (11.11%) had low risk, two patients had intermediate risk (3.33%), and three patients (25%) had high risk in the D'Amico scale.
Recurrence of PSA
About the recurrence of PSA, we found 16 (14.81%) patients; five patients had low risk (13.89%), and 11 patients had intermediate risk (18.33%). No patient with high risk had recurrence.
Adjuvant treatment
During the following time after surgery, 46 (42.59%) patients received adjuvant treatment with radiotherapy (76-81 Gy) and/or hormonal treatment. Of these patients, 16 (44.44%) were evaluated as low risk, 22 (36.67%) as intermediate risk, and eight (66.67%) as high risk. All this data are shown detailed in Table 2.
Tabla 2 Results by risk groups according to D'Amico for persistence and recurrence of PSA, characteristics of the surgical piece and adjuvant treatment
| Risk groups | Low | Intermediate | High | Total | χ2 | P | Cramer's V |
|---|---|---|---|---|---|---|---|
| Adverse characteristics of the surgical piece | |||||||
| Adverse | 5 (13.89%) | 17 (28.33%) | 6 (50%) | 28 (25.93%) | 6.52 | 0.0434* | 0.246 |
| No adverse | 31 (86.11%) | 43 (71.67%) | 6 (50%) | 80 (74.07%) | |||
| Persistence of PSA | |||||||
| Persistence | 4 (11.11%) | 2 (3.33%) | 3 (25.00%) | 9 (8.33%) | 6.69 | 0.0302* | 0.249 |
| No persistence | 32 (88.89%) | 58 (96.67%) | 9 (75.00%) | 79 (91.67%) | |||
| Recurrence of PSA | |||||||
| Recurrence | 5 (13.89%) | 11 (18.33%) | 0 (0%) | 16 (14.81%) | 2.7 | 0.3309* | 0.158 |
| No Recurrence | 31 (86.11%) | 49 (81.67%) | 12 (100%) | 92 (85.19%) | |||
| Adjuvant treatment | |||||||
| Treatment | 16 (44.44%) | 22 (36.67%) | 8 (66.67%) | 46 (42.59%) | 3.76 | >0.05 | 0.186 |
| No treatment | 20 (55.56%) | 38 (63.33%) | 4 (3.33%) | 62 (57.41%) |
*Fisher exact probability test. PSA: prostate-specific antigen.
Post-surgical Gleason score analysis
About the increase of post-surgical Gleason score, it was observed in 16 (44.44%) patients evaluated as low risk by D'Amico scale; moreover, in 16 (26.67%) patients evaluated as intermediate risk and in 5 (41.67%) patients evaluated as high risk (Table 3).
Tabla 3 Variation of Gleason score following radical prostatectomy by risk group according to D'Amico classification
| Risk groups | Gleason | ||||||
|---|---|---|---|---|---|---|---|
| Increase | |||||||
| n (%) | Decrease | Same | Total | χ2 | p | Cramer's V | |
| Low | 16 (44.44) | n (%) | n (%) | n (%) | |||
| Intermediate | 16 (26.67) | 0 (0) | 20 (55.56) | 36 (100) | 1.86 | 0.172 | 0.1518 |
| High | 5 (41.67) | 13 (21.66) | 31 (51.67) | 60 (100) | 2.74 | 0.0978 | 0.179 |
| Total | 37 (34.26) | 1 (8.33) | 6 (50) | 12 (100) | 0.392* | 0.0533 | |
| *Fisher exact probability test | 14 (12.96) | 57 (54.29) | 108 (100) | ||||
Discussion
This study evaluated 108 patients with localized prostate cancer who underwent radical prostatectomy. They were classified into risk groups according to D'Amico scale, the most prevalent was the intermediate risk (55.56%). We found a PSA recurrence rate of 14.81%, lower than the reported in international studies (23-34%); moreover, the mortality reported in the follow-up was 6%2. In our hospital, only one death was identified (acute myocardial infarction), 2 weeks after surgery; no deaths were identified in the follow-up of localized prostate cancer disease after radical prostatectomy, neither in patients who merited adjuvant treatment. In our study, in the high-risk group, no patients had recurrence, possibly due to the sample size; nevertheless, we cannot underestimate the effect of patient selection before surgery in the institution, specifically in their risk classification. It was observed that the average age was 65.3 ± 5.91 years, similar to the reported in other studies (63-68 years)16-18. The main comorbidities were also evaluated, being type 2 diabetes mellitus (15.74%) and arterial hypertension (29.63%) the most frequent; considering that the metabolic syndrome is associated in different studies to increasing risk of prostate cancer19.
The pathological diagnosis of localized prostate cancer was performed in 92.59% by transrectal biopsy, while 7.4% were performed by transurethral resection of the prostate. In international studies, it was found that prostate cancer was diagnosed in 98.7% by transrectal biopsy and the rest by transurethral resection of the prostate2. In Mexico, prostate cancer is diagnosed by transrectal prostate biopsy in 77% of the patients and by transurethral resection of the prostate in 17% of the patients20. The results of our hospital are similar with international studies; but, comparing with Mexico, the percentage decreases by transrectal prostate biopsy, because patients do not have a screening and come for obstructive prostatic hyperplasia performing transurethral resection of the prostate. Surgical management of patients was performed by open and laparoscopic surgery. Open surgery was the most frequent technique in the present study, with retropubic radical prostatectomy in 64 patients (59.26%), retropubic radical prostatectomy plus pelvic lymphadenectomy in 32 patients (29.63%), and laparoscopic surgery in 12 patients (11.11%) who were classified as low risk. Lymphadenectomy is not necessary in patients with low-risk prostate cancer since the risk of positive lymph node involvement does not exceed 5%. In intermediate risk, lymphadenectomy is performed if the positive lymph nodes are >5% and in those of high risk it should be performed to all2.
The decision to perform lymphadenectomy in radical prostatectomy uses the nomograms of the Memorial Sloan Kettering Center, Briganti nomograms representing a discriminating power superior to the Partin tables2. Therefore, 40 patients classified as intermediate risk brfore surgery did not undergo pelvic lymphadenectomy because it was <5% of the calculated probability of lymph node involvement. All patients classified as high risk underwent lymphadenectomy. Average bleeding was 842.03 ± 600.20 mL.
Radical prostatectomy represents one of the treatments of choice for patients with localized prostate cancer and it is associated with good long-term outcomes2. However, more than 30-35% of contemporary patients treated with radical prostatectomy will present adverse features to the disease (extracapsular extension, invasion of seminal vesicles, or positive margins) in the final pathology exam20. We found 28 patients (25.93%) that presented adverse characteristics in the surgical piece, being lesser than the international reports. In the present study, we found the following results: about 13.89%, 28.33%, and 50% for low, intermediate, and high-risk groups, respectively; on the other hand, results of information in the international literature show 16%, 41%, and 66% for low, intermediate, and high-risk groups, respectively. These percentages are higher, but the ratio of distribution is similar to the literature21.
While evaluating the persistence of PSA, it was found that nine patients (8.33%) presented persistence of it, being low-risk four patients (11.11%), intermediate-risk two patients (3.33%), and high-risk three patients (25%). In different international articles, biochemical persistence occurs in approximately 20% of patients22,23, comparing with our study, only 8.33% were low. After surgery, PSA is expected to become undetectable at approximately 6 weeks postoperatively. However, up to 20% of patients with adverse pathologic features do not achieve an undetectable PSA level after radical prostatectomy23.
Adjuvant treatment after radical prostatectomy is to add to the primary therapy to decrease the risk of relapse. Adjuvant treatment to radical prostatectomy is performed with radiation therapy with or without androgen deprivation therapy. The combination of radiation therapy with androgen deprivation therapy has been shown to be superior to radiation therapy alone.
All prostate cancer patients high-risk should be given multimodal treatment (androgen deprivation therapy and/or radiotherapy)2.
Adjuvant therapy should be offered to the surgical field to patients with a higher risk of local relapse: pT3 pN0 with positive margins (greater impact) and/or invasion of the seminal vesicles. Patients can be offered pN + adjuvant therapy: (1) androgen deprivation therapy by pN + and (2) androgen deprivation therapy with additional radiotherapy2.
In patients with high risk or adverse features in the surgical piece, surgery alone may not provide adequate long-term oncologic control. Therefore, a multimodal approach including radiotherapy with or without hormone deprivation therapy should be considered. Adjuvant radiation therapy is defined as the administration of radiation therapy to the prostate bed, seminal vesicle bed, and pelvic lymph node area that is typically administered 1-6 months after surgery in the absence of signs of recurrence. Prospective randomized trials support the role of radiotherapy in the risk reduction of biochemical recurrence. However, more than 40% of patients treated with initial observation will not resort to 10 years follow-up. Possible short- and long-term side effects associated with adjuvant radiotherapy, as well as the inconvenience and expense should be considered in the oncological benefit. Consequently, adjuvant radiotherapy is administered in approximately 20% of patients in contemporary series with adverse pathological features in first world countries20. In our study, 46 patients (42.59%) received adjuvant treatment as part of the complementary treatment, being more than double when compared with first world countries. Adjuvant was given to those patients with adverse characteristics to the surgical specimen, those who presented persistence or recurrence of the disease. Therefore, a multimodal approach was given that included: radiotherapy with or without hormone deprivation therapy to the 46 patients who received complementary treatment. We observed that the adjuvant treatment is higher in low-risk patients (44.44%), it is expected that in this risk group the percentage is low; this may be due to the elevation of the Gleason score that was obtained in low-risk patients. This may be a bad result of the prostate biopsy to have the different cores in quality and quantity, not getting adequate results and this influence the result of the biopsy. With 66.67% of high-risk patients receiving adjuvant treatment, this trend was found in the international literature, where they receive complementary treatment after surgery. In different international studies, the increase in the total Gleason score after surgery is 52-54% with an increase in the primary grade of Gleason with or without the increase in the total score of Gleason24. Our study showed a 34.26% increase in the total Gleason score after surgery, being low compared to international studies. Therefore, Gleason score after surgery was evaluated, divided into risk groups, finding that 16 patients (44.44%) of low-risk increased the Gleason score, 16 patients (26.67%) of intermediate-risk increased the Gleason score after surgery, and five patients (41.67%) of high-risk increased Gleason score. The low-risk patients' percentage was higher; this could be due to a poor classification of the risk group, a poor pathology report or a poor sampling when performing transurethral prostate biopsy, which influences the patient's risk classification.
Our institution provides free medication to patients with a health insurance government program, as well as radiotherapy, being an advantage in treatment and prevents abandonment, because most of the population attended is of low socioeconomic and educational level. We cannot deny that the retrospective nature affects the data collected about the disease evolution and some patients were lost in the monitoring of the disease by many reasons, such as migration or living in remote areas. Patients are routinely asked about urinary incontinence and erectile dysfunction, complications expected in radical prostatectomy, but some records did not report the evolution of these complications. In national and international studies, urinary incontinence after radical prostatectomy varies between 27% and 35% and erectile dysfunction in 25% and 75% of cases following surgery25. Prospective longitudinal studies on urinary incontinence and erectile dysfunction following radical prostatectomy may be performed in the future, as well as evaluating the survival of patients.
Conclusions
Based on our results, we consider important to make an adequate risk classification of patients with prostate cancer located before surgery. This action provides an appropriate oncological management. We consider that an adequate classification and selection of patients who received medical and surgical treatment allowed us to obtain low recurrence rates. The recurrence rate of PSA was lower compared to international studies, probably due to the adequate selection of patients in the institution. No death from prostate cancer was reported in the follow-up of the disease. In high-risk patients, no recurrences were observed, possibly due to a small sample size, but we consider important to state that 42.59% of patients received adjuvant treatment, and 25.93% of patients had adverse characteristics in the surgical piece.
