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Pathologic Prostate Cancer Characteristics in Patients Eligible for Active Surveillance: A Head-to-Head Comparison of Contemporary Protocols

BACKGROUND Although the rationale for active surveillance (AS) in patients with low-risk prostate cancer is well established, eligibility criteria vary significantly across different programs. OBJECTIVE To compare the ability of contemporary AS criteria to identify patients with certain pathologic tumor features based on the results of an extended transrectal prostate biopsy. DESIGN, SETTINGS, AND PARTICIPANTS The study cohort included 391 radical prostatectomy patients who had prostate cancer with Gleason scores ≤ 6 on transrectal biopsy with ≥ 10 cores. INTERVENTION Radical prostatectomy without neoadjuvant treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We identified patients who fulfilled the inclusion criteria of five AS protocols including those of Epstein, Memorial Sloan-Kettering Cancer Center, Prostate Cancer Research International: Active Surveillance (PRIAS), University of California, San Francisco, and University of Miami (UM). We evaluated the ability of these criteria to predict three pathologic end points: insignificant disease defined using a classical and updated formulation, and organ-confined Gleason ≤ 6 prostate cancer. Measures of diagnostic accuracy and areas under the receiver operating curve were calculated for each protocol and compared. RESULTS AND LIMITATIONS A total of 75% of the patients met the inclusion criteria of at least one protocol; 23% were eligible for AS by all studied criteria. The PRIAS and UM criteria had the best balance between sensitivity and specificity for both definitions of insignificant prostate cancer and a higher discriminative ability for the end points than any criteria including patients with two or more positive cores. The Epstein criteria demonstrated high specificity but low sensitivity for all pathologic end points, and therefore the discriminative ability was not superior to those of other protocols. CONCLUSIONS Significant variations exist in the ability of contemporary AS criteria to predict pathologically insignificant prostate cancer at radical prostatectomy. These differences should be taken into account when making treatment choices in patients with low-risk prostate cancer.

Prostate Sampling by 12-Core Biopsy: Comparison of the Biopsy Results With Tumor Location in Prostatectomy Specimens

OBJECTIVE To analyze the diagnostic performance of individual prostate biopsy cores. The 12-core transrectal prostate biopsy scheme has emerged as a standard of care. However, quality of sampling may vary in different areas of the prostate included in this procedure. MATERIAL AND METHODS Two-hundred fifty men underwent radical prostatectomy at our institution. All participants had a systematic 12-core transrectal prostate biopsy containing lateral and medial cores from each side of the apical, medial and basal thirds of the prostate. Biopsy results were matched with histologic maps of the prostatectomy specimens. Sensitivity, negative predictive value (NPV), and overall accuracy were calculated for each biopsy core location and compared between different groups of cores. In addition, patients in the upper quartile of prostate weight were compared with the rest of the cohort. RESULTS Sensitivity, NPV, and overall accuracy were significantly lower for apical cores. Average NPV and overall accuracy of basal and mid-lateral biopsies were inferior to those of medial biopsies on the same levels. However, sensitivity of these lateral cores was similar to that of the medial cores. Sensitivities of apical and mid cores were significantly lower in patients with larger prostates. CONCLUSION Decreased accuracy in lateral mid- and basal cores results from higher frequencies of cancer in corresponding prostate areas, and therefore additional samples should be taken at these locations. In addition, diagnostic accuracy of apical cores may be improved through better targeting of the prostatic apex. This may be particularly important in patients with larger prostates.

Prostate Cancers of Different Zonal Origin: Clinicopathological Characteristics and Biochemical Outcome After Radical Prostatectomy

OBJECTIVE To evaluate the effect of prostate cancer zonal origin on the biochemical outcome after radical prostatectomy, to analyze clinicopathological features of tumors arising in different zones and to test the ability of the nomogram to predict the probability of transition zone cancer at radical prostatectomy. METHODS Our cohort consisted of 1441 patients who underwent radical prostatectomy who did not receive neoadjuvant treatment. Clinicopathological characteristics and biochemical outcomes were compared between the groups of men with different zonal location of prostate cancer. Performance of the nomogram in predicting cancer location was evaluated with respect to discrimination and calibration. RESULTS The rates of positive margin were similar in men with transition zone and mixed tumors and were significantly higher than those with peripheral zone tumors. Most of the positive margins in patients with transition zone and mixed cancers were located at the apico-anterior part of the gland. On multivariate analysis, transition zone cancer location was associated with better biochemical recurrence-free survival (P = .043). The Harrel c-index of the models that did and did not include zonal origin of cancer was 0.810 and 0.807, respectively. Performance of the nomogram was poor. CONCLUSION The association between transition zone tumor origin and the risk of biochemical recurrence does not add important predictive value to the standard prognostic factors. Although information about the risk of prostate cancer involvement of the transition zone may be important for surgical planning, our ability to predict this risk preoperatively is limited.

Clinically significant gleason sum upgrade: External validation and head-to-head comparison of the existing nomograms

Several nomograms have been developed for the purpose of predicting the likelihood of an increase in Gleason sum (GS) from biopsy information compared with the GS determined after examination of the “entire prostate” in patients with prostate cancer. In this study, the authors evaluated and compared the ability of 4 nomograms (published by Capitanio et al, Chun et al, Kulkarni et al, and Moussa et al) to predict GS upgrades for patients with biopsy GS ≤6 prostate cancer who underwent radical prostatectomy (RP) at their center.

Partial Sampling of Radical Prostatectomy Specimens Detection of Positive Margins and Extraprostatic Extension

Currently there is no global agreement as to how extensively a radical prostatectomy specimen should be sectioned and histologically examined. We analyzed the ability of different methods of partial sampling in detecting positive margin (PM) and extraprostatic extension (EPE)—2 pathologic features of prostate cancer that are most easily missed by partial sampling of the prostate. Radical prostatectomy specimens from 617 patients treated with open radical prostatectomy between 1992 and 2011 were analyzed. Examination of the entirely submitted prostate detected only PM in 370 (60%), only EPE in 100 (16%), and both in 147 (24%) specimens. We determined whether these pathologic features would have been diagnosed had the examination of the specimen been limited only to alternate sections (method 1), alternate sections representing the posterior aspect of the gland in addition to one of the mid-anterior aspects (method 2), and every section representing the posterior aspect of the gland in addition to one of the mid-anterior aspects, supplemented by the remaining ipsilateral anterior sections if a sizeable tumor is seen (method 3). Methods 1 and 2 missed 13% and 21% of PMs and 28% and 47% of EPEs, respectively. Method 3 demonstrated better results missing only 5% of PMs and 7% of EPEs. Partial sampling techniques missed slightly more PMs and EPEs in patients with low-risk to intermediate-risk prostate cancer, although even in high-risk cases none of the methods detected all of the studied aggressive pathologic features.

Tumor focality is not associated with biochemical outcome after radical prostatectomy

The clinical and prognostic significance of unifocal prostatic carcinoma is not clearly understood. In the current study, we sought to characterize the clinical and pathologic characteristics of unifocal and multifocal prostate cancers and to investigate the effects of tumor focality on biochemical outcome after radical prostatectomy.

Prognostic Implications of Partial Sampling of Radical Prostatectomy Specimens: Comparison of 3 Methods

PURPOSE We analyzed the prognostic implications of positive margins and extraprostatic extension missed by different methods of partially sampling prostatectomy specimens. MATERIALS AND METHODS The study group consisted of 1,499 patients treated with radical prostatectomy. All specimens were processed uniformly and submitted entirely. For each patient with a positive margin or extraprostatic extension we determined whether these pathological characteristics would have been diagnosed had the specimen been examined by 3 partial sampling techniques. The Harrell concordance index was used to quantify the predictive performance of the Cox models based on the potential findings of the different sampling methods. RESULTS Partial sampling methods 1 and 2, which included the examination of alternate slides, missed 13% to 21% of positive margins and 27% to 46% of extraprostatic extensions. The effect on biochemical recurrence-free survival of these undetected pathological features was similar to that of positive margins and extraprostatic extension that would have been diagnosed by corresponding techniques. Method 3, which sampled the entire posterior region, the mid anterior prostate and the rest of the ipsilateral anterior gland (if sizeable tumor was seen), detected 95% of positive margins and 94% of extraprostatic extensions. The extraprostatic extension missed by this method was not associated with a significant increase in the risk of biochemical recurrence. The Harrell concordance index of the multivariate models was 0.806, 0.797, 0.795 and 0.804 based on the results of complete sampling, and methods 1, 2 and 3, respectively. CONCLUSIONS Examining alternate sections of prostatectomy specimen results in missing clinically important positive margins and extraprostatic extension. It decreases our ability to predict biochemical recurrence-free survival.

Twin Reversed Arterial Perfusion Sequence (TRAPS): An Illustrative Series of 13 Cases

ABSTRACT Twin reversed-arterial-perfusion sequence (TRAPS) is a rare and severe complication of monochorionic twin pregnancies. It usually occurs in the setting of monochorionic placentation, when the heart of a normal appearing twin serves as the pump for one or more dysmorphic twins whose head, thoracic organs, and upper extremities do not fully develop or do not develop at all and thus lack cardiac activity. Anomalous vascular placental architecture causes a shift in arterial flow towards the acardiac twin(s). The exact physiopathologic mechanisms that lead to this devastating phenomenon are not well known. We reviewed the maternal history and the surgical pathology reports of the fetuses and placentas of 13 different cases of TRAPS that were collected in a 23-year study period at a single institution. Herein we summarize the characteristic findings and illustrate specific mechanical feto-placental circulation issues that appear to be instrumental in the development of TRAPS.

Lack of Association between COX-2 Staining Level and Biochemical Recurrence Following Salvage Radiation Therapy for Recurrent Prostate Cancer.

ObjectiveThe ability to predict which men will experience biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer following radical prostatectomy has potential for improvement. Cyclooxygenase-2 (COX-2) overexpression has previously correlated with poor clinical outcomes following primary treatment for prostate cancer; however, its predictive ability in the specific setting of SRT has not been examined to date. This study evaluated the association between COX-2 staining intensity and BCR following SRT for recurrent prostate cancer.MethodsWe utilized a cohort of 151 patients who underwent SRT between July 1987 and July 2003. COX-2 staining intensity in primary tumor samples was detected using monoclonal antibodies and quantified using a computer-assisted method. The association between COX-2 staining intensity and BCR was evaluated using multivariable Cox regression models.ResultsWhen examining COX-2 staining level as three-level categorical variable (low, moderate, high) based on approximate sample tertiles, there was no evidence of an association with BCR (P = 0.18). More specifically, in comparison to patients with low staining intensity, there was no significant difference in risk of BCR for moderate (relative risk [RR], 1.17; P = 0.56) or high (RR, 0.72; P = 0.22) COX-2 staining intensity patients. This lack of association was also observed when considering COX-2 staining intensity as a continuous variable (RR, 0.83; P = 0.15).ConclusionOur results indicate that COX-2 staining intensity is likely of little use in discriminating prognosis of SRT. It appears that the search for prognostic factors associated with BCR should continue elsewhere in order to further enhance patient selection for SRT.

A unique presentation and rare pathological finding for urachal sinus

We report an otherwise well developing 2-year-old girl who presented with a urachal sinus with its opening located at the midline between umbilicus and the pubic symphysis. Diagnosis was made by ultrasound preoperatively, and confirmed during surgery. Additionally, columnar epithelium was found in the portion of sinus tract traversing the abdominal wall. Metaplasia of the sinus tract is worrisome, as urachal carcinomas have been traditionally characterized to result from this process.