Alexandre C. Sant'Anna

Perineural invasion detection in prostate biopsy is related to recurrence-free survival in patients submitted to radical prostatectomy.

OBJECTIVE Perineural invasion (PNI) is detected in almost 20% of prostate biopsies and has been related to worse prognostic factors in radical prostatectomy (RP) specimens and lower disease-free survival rates. The aim of this study was to evaluate the importance of PNI during periods of extended prostate biopsies and to determine the value of this preoperative parameter as a predictor of pathologic findings in surgical specimens and in biochemical recurrence. MATERIALS AND METHODS Between 2001 and 2009, 599 prostate biopsies and their respective RP specimens were examined in our laboratory. The RP specimens were always examined completely. The mean age of the patients was 61 years, and the mean PSA was 6.4 ng/mL. The mean and median number of biopsy cores obtained was 14.4 and 14, respectively. PNI was identified in 105 biopsies (17.5%). We studied the ability of PNI in prostate biopsies to determine the tumor stage in surgical specimens and the relationship of PNI with biochemical recurrence during a mean follow-up time of 51.4 months. RESULTS The presence of PNI in prostate biopsies was observed in older patients (63 vs. 61 years old, P = 0.008). All of the prognostic factors determined for the RP specimens were significantly worse in patients with PNI compared with those without PNI. PNI was strongly associated with a higher pathologic stage (87% specificity, 40% sensitivity, odds ratio 4.8). Stage pT3 prostatic cancer was determined in 46 (43.8%) of 105 patients with PNI on biopsy compared to 69 (14%) of 494 patients without PNI (P = 0.01). Fifty-six (19.6%) patients had a biochemical recurrence, and PNI correlated significantly with PSA recurrence. A Kaplan-Meier analysis revealed a significant difference in recurrence-free survival between patients with and without PNI (45% vs. 53%, respectively, P = 0.021, log-rank test = 0.19). CONCLUSION PNI is an important morphologic preoperative predictor of the pathologic stage as well as biochemical recurrence and must always be mentioned when adenocarcinoma is diagnosed on prostate biopsies.

Sarcomatoid differentiation in renal cell carcinoma: prognostic implications

INTRODUCTION Renal cell carcinoma with sarcomatoid differentiation is a tumor with aggressive behavior that is poorly responsive to immunotherapy. The objective of this study is to report our experience in the treatment of 15 patients with this tumor. MATERIALS AND METHODS We retrospectively analyzed 15 consecutive cases of renal cell carcinoma with sarcomatoid differentiation diagnosed between 1991 and 2003. The clinical presentation and the pathological stage were assessed, as were the tumors pathological features, use of adjuvant immunotherapy and survival. The studys primary end-point was to assess survival of these individuals. RESULTS The sample included 8 women and 7 men with mean age of 63 years (44-80); follow-up ranged from 1 to 100 months (mean 34). Upon presentation, 87% were symptomatic and 4 individuals had metastatic disease. Mean tumor size was 9.5 cm (4-24) with the following pathological stages: 7% pT1, 7% pT2, 33% pT3, and 53% pT4. The pathological features showed high-grade tumors with tumoral necrosis in 87% of the lesions and 80% of intratumoral microvascular invasion. Disease-free and cancer-specific survival rates were 40 and 46% respectively, with 2 cases responding to adjuvant immunotherapy. CONCLUSIONS Patients with sarcomatoid tumors of the kidney have a low life expectancy, and sometimes surgical resection associated with immunotherapy can lead to a long-lasting therapeutic response.

Are we able to correctly identify prostate cancer patients who could be adequately treated by focal therapy

INTRODUCTION AND OBJECTIVE Because of the improvements on detection of early stage prostate cancer over the last decade, focal therapy for localized prostate cancer (PC) has been proposed for patients with low-risk disease. Such treatment would allow the control of cancer, thereby diminishing side effects, such as urinary incontinence and sexual dysfunction, which have an enormous impact on quality of life. The critical issue is whether it is possible to preoperatively predict clinically significant unifocal or unilateral prostate cancer with sufficient accuracy. Our aim is to determine whether there is any preoperative feature that can help select the ideal patient for focal therapy. MATERIAL AND METHODS A total of 599 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy followed by radical prostatectomy to treat PC were examined in our laboratory between 2001 and 2009. We established very restricted criteria to select patients with very-low-risk disease for whom focal therapy would be suitable (only 1 biopsy core positive, tumor no larger than 80% of a single core, no perineural invasion, PSA serum level < 10 ng/ml, Gleason score < 7 and clinical stage T1c, T2a-b). We defined 2 groups of patients who would be either adequately treated or not treated by focal therapy. The primary endpoint was the evaluation of preoperative features in order to identify which parameters should be considered when choosing good candidates for focal therapy. RESULTS Fifty-six out of 599 patients met our criteria. The mean age was 59 years, and the mean number of biopsy cores was 14.4. Forty-seven (83.9%) were staged T1c, and 9 (16.1%) were staged T2a-b. Forty-four (78.6%) patients could be considered to have been adequately treated by focal therapy, and 12 (21.4%) could not. There was no statistical difference between the 2 groups considering age, clinical stage, PSA levels, Gleason score, and tumor volume in the biopsy. All 12 patients who could be considered inadequately treated had a bilateral, significant secondary tumor, 58.3% had Gleason ≥ 7, and 25% were staged pT3. CONCLUSION Although focal therapy might be a good option for patients with localized prostate cancer, we are so far unable to select which of them would benefit from it based on preoperative data, even using very restricted criteria, and a considerable proportion of men would still be left undertreated.

Desdiferenciação do câncer da próstata após terapia antiandrogênica

BACKGROUND: Neoadjuvant androgen deprivation in prostate cancer induces tumor volume regression but does not improve outcome of the patient. A possible explanation for this phenomenon could be an increase of the residual tumor aggressiveness brought about by antiandrogen therapy. The purpose of the present study was to evaluate the frequency of tumor dedifferentiation following androgen blockade in prostate cancer and to determine if the remaining tumor shows signs of increased aggressiveness. METHODS: Thirty patients bearing locally advanced prostate cancer (stages T2c - T3) were submitted to neoadjuvant anti-androgenic therapy during four months followed by radical prostatectomy. Gleason scores from biopsy and surgical specimens were compared. Furthermore, the cell proliferation index was evaluated by immunohistochemistry assay for PCNA, tests with strong nuclear staining were considered positive. The percentage of positive nuclei, counted in 500 cells, was determined in several categories of the Gleason score from surgical specimens. RESULTS: In 11(37%) surgical specimens the Gleason score was equal or lower than that found in the biopsy and in 19 (63%) the total score was higher in the surgical specimens (p 0.05). The median of cell proliferation indexes was 9% for glandular or specimen confined tumors and was 17% for extraprostatic tumors (p<0.05). CONCLUSION: The lower Gleason score was found in almost 2/3 of patients submitted to antiandrogen therapy. However, the cell proliferation index measured by PCNA was the same for tumors with lower or higher Gleason scores. It seems that cell dedifferentiation seen after neoadjuvant androgen deprivation represents a mere morphologic phenomenon and not a real increase in tumor aggressiveness.

Prognostic value of the percentage of positive fragments in biopsies from patients with localized prostate cancer

OBJECTIVE To assess the prognostic value of the percentage of positive fragments (PPF) in biopsies from patients with localized prostate cancer (PCa) undergoing radical prostatectomy. MATERIALS AND METHODS During the period from March 1991 to November 2000, 440 patients were selected. Cases receiving neoadjuvant or adjuvant hormone therapy, or adjuvant radiotherapy, were excluded, as were cases presenting Gleason scores higher than 6 at biopsy. PPF was defined as the total number of fragments divided by the total number of biopsy fragments times 100. This variable was initially divided into categories from 0 to 25%, 25.1% to 50%, 50.1 to 75% and 75% to 100%. During the postoperative period, patients were assessed every 2 months for 1 year, then every 6 months for 5 years, and then yearly. Biochemical recurrence was defined as serum PSA higher than or equal to 0.4 ng/mL. Median follow-up was 60 months. RESULTS One hundred and nine (24.8%) of the 440 patients under study had biochemical recurrence. In the univariate analysis, PPF significantly influenced disease-free survival (log-rank, p < 0.001), and patients with PPF between 75 and 100% presented a risk of a biochemical recurrence of the disease 3 times higher than patients with PPF between 0 and 25% (p < 0.001). After the Cox regression analysis, both serum PSA (p = 0.001) and PPF (p < 0.001) showed to be independent predictive factors for disease-free survival following surgery. CONCLUSION PPF measurement in biopsy is a simple and practical method, which should be routinely used as a predictive factor for biochemical recurrence in patients with PCa presenting Gleason scores between 2 and 6.

Analysis of risk factors of involvement of seminal vesicles in patients with prostate cancer undergoing radical prostatectomy

OBJECTIVE To determine through preoperative serum PSA level, Gleason score on biopsy and percentage of fragments affected by tumor on biopsy, the probability of involvement of the seminal vesicles. MATERIALS AND METHODS During the period between March 1991 to December 2002, we selected 899 patients undergoing radical prostatectomy for treatment of localized prostate adenocarcinoma. The analyzed preoperative variables were PSA, percentage of positive fragments and Gleason score on the biopsy. Pre-operative PSA was divided in scales from 0 to 4.0 ng/mL, 4.1 to 10 ng/mL, 10.1 to 20 ng/mL and > 20 ng/mL, Gleason score was categorized in scales from 2 to 6. 7 and 8 to 10, and the percentage of affected fragments was divided in 0 to 25%, 25.1% to 50%, 50.1% to 75%, and 75.1% to 100%. All these variables were correlated with the involvement of seminal vesicles in the surgical specimen. RESULTS Of the 899 patients under study, approximately 11% (95% CI, [9% - 13%]) had involvement of seminal vesicles. On the multivariate analysis, when PSA was < or = 4, the Gleason score was 2 to 6, and less than 25% of fragments were involved on the biopsy, only 3.6%, 7.6% and 6.2% of patients respectively, had involvement of seminal vesicles. On the multivariate analysis, we observed that PSA, Gleason score and the percentage of involved fragments were independent prognostic factors for invasion of seminal vesicles. CONCLUSION The preoperative variables used in the present study allow the identification of men with minimal risk (lower than 5%) if involvement of seminal vesicles.