Predicting unilateral prostate cancer on routine diagnostic biopsy: sextant vs extended.

OBJECTIVE: To compare the diagnostic properties of routine office-based sextant and extended biopsies for unilateral prostate cancer, as validated by final pathology, because focal therapy of prostate cancer is gaining acceptance as a viable treatment option and thus patient selection is of paramount consideration. PATIENTS AND METHODS: We retrospectively analysed records of patients who had a radical prostatectomy (RP) for biopsy confirmed prostate cancer at our institution between 1990 and 2007. Records with incomplete data were excluded. Diagnostic properties for sextant and extended biopsies were calculated and compared for diagnostic accuracy, sensitivity, specificity, positive and negative predictive values (PPV, NPV) and false-positive and -negative rates. RESULTS: We identified 882 records (729 sextant, 153 extended biopsies) matching our criteria. Overall, unilateral prostate cancer was confirmed in 151 (16%) of pathological RP specimens. The sensitivity improved from 84.1% to 88.0% on sextant and extended biopsy, respectively. Similarly, the PPV increased from 21.9% to 27.2%, specificity from 37.1% to 53.9% (P < 0.05), and NPV from 91.8% to 95.8% (P < 0.05). These changes are reflected in the decrease in false-positive rates (from 62.9% to 46.1%) and false-negative rates (from 15.9% to 12.0%). The overall diagnostic accuracy increased from 49% on sextant to 59% on extended biopsy (P < 0.05). CONCLUSIONS: Taking more prostate biopsy cores improves the diagnostic properties for identifying unilateral prostate cancer. However, a 12-core biopsy is not an ideal diagnostic test to select patients for focal therapy, and should be interpreted in conjunction with imaging and clinical variables. Additional research should investigate the diagnostic gain associated with a further increase in the number of biopsy cores.

Current salvage methods for recurrent prostate cancer after failure of primary radiotherapy.

We reviewed the current salvage methods for patients with local recurrent prostate cancer after primary radiotherapy (RT), using a search of relevant Medline/PubMed articles published from 1982 to 2008, with the following search terms: 'radiorecurrent prostate cancer, local salvage treatment, salvage radical prostatectomy (RP), salvage cryoablation, salvage brachytherapy, salvage high-intensity focused ultrasound (HIFU)', and permutations of the above. Only articles written in English were included. The objectives of this review were to analyse the eligibility criteria for careful selection of appropriate patients and to evaluate the oncological results and complications for each method. There are four whole-gland re-treatment options (salvage RP, salvage cryoablation, salvage brachytherapy, salvage HIFU) for RT failure, although others might be in development or investigations. Salvage RP has the longest follow-up with acceptable oncological results, but it is a challenging technique with a high complication rate. Salvage cryoablation is a feasible option, especially using third-generation technology, whereby the average biochemical disease-free survival rate is 50-70% and there are fewer occurrences of severe complications such as recto-urethral fistula. Salvage brachytherapy, with short-term cancer control, is comparable to other salvage methods but depends on cumulative dosage limitation to target tissues. HIFU is a relatively recent option in the salvage setting. Both salvage brachytherapy and HIFU require more detailed studies with intermediate and long-term follow-up. As these are not prospective, randomized studies and the definitions of biochemical failure varied, there are limited comparisons among these different salvage methods, including efficacy. In the focal therapy salvage setting, the increased use of thermoablative methods for eligible patients might contribute to reducing complications and maintaining quality of life. The problem to effectively salvage patients with locally recurrent disease after RT is the lack of diagnostic examinations with sufficient sensitivity and specificity to detect local recurrence at an early curable stage. Therefore, a more strict definition of biochemical failure, improved imaging techniques, and accurate specimen mapping are needed as diagnostic tools. Furthermore, universal selection criteria and an integrated definition of biochemical failure for all salvage methods are required to determine which provides the best oncological efficacy and least comorbidity.

Use of 111in-capromab pendetide immunoscintigraphy to image localized prostate cancer foci within the prostate gland.

PURPOSE: We compared the results of a preoperative (111)In-capromab pendetide scan co-registered with computerized tomography with pathological findings in the surgically excised prostate to determine whether the scan can efficiently detect cancer in the prostate. MATERIALS AND METHODS: This prospective trial included 25 hormone naïve men with clinically localized prostate cancer who underwent (111)In-capromab pendetide single photon emission computerized tomography/computerized tomography as part of the preoperative evaluation. In addition to routine histological analysis, representative prostate sections were stained for prostate specific membrane antigen using the same antibody used in the scan. A pathologist and a radiologist were blinded to pathology and imaging findings, respectively. Prostate specific membrane antigen immunohistochemistry was correlated with the 3-dimensional location of the prostate specific membrane antigen signal detected by scan. RESULTS: Scan sensitivity was 37% to 87% for 4 quadrants (right vs left and apical vs basal) with 0% to 50% specificity, as validated by final pathological assessment of the same quadrants. Stratifying positive scan signal strength did not statistically improve specificity (p = 0.35). There was no significant correlation between prostate specific membrane antigen over expression and tumor stage distribution (p = 0.23). CONCLUSIONS: The scan did not localize prostate cancer to a particular quadrant based on comparison with radical prostatectomy specimen pathology. The antibody used has affinity for benign and malignant prostatic glands in excised, formalin fixed prostate tissue, which may contribute to low scan specificity in vivo. The scan cannot be used to reliably detect or image cancer foci in the prostate.

Nerve-sparing focal cryoablation of prostate cancer.

PURPOSE OF REVIEW: We evaluate the rationale, candidate selection, and results of the first clinical studies of focal cryoablation for select patients with low volume and low-to-low - moderate risk features of prostate cancer as a possible alternative to whole gland treatment. RECENT FINDINGS: For a select cohort of patients with low-to-low - moderate risk unifocal or unilateral prostate cancer, a number of ablative treatment options for focal therapy are available with cryotherapy having the most clinical experience. However, retrospective pathological data from large prostatectomy series do not clearly reveal valid and reproducible criteria to select appropriate candidates for focal cryoablation due to the complexity of tumorigenesis in early stage disease. SUMMARY: The concept of focal therapy is evolving with the understanding of the biologic variability (clinically aggressive, significant, or insignificant) of prostate cancers that may require different treatment approaches. Minimally-invasive, parenchyma-preserving cryoablation can be considered as a potential feasible option in the treatment armamentarium of early stage, localized prostate cancer in appropriately selected candidates.

Utility of a 3-dimensional transrectal ultrasound-guided prostate biopsy system for prostate cancer detection.

The 3-D transrectal ultrasound (TRUS)-guided prostate biopsy system is a novel device that allows precise needle placement in a template fashion. We evaluate its utility for prostate cancer (PCa) detection. A retrospective analysis was performed evaluating 68 prospective patients at the Duke Prostate Center who underwent a prostate biopsy using a 3-D TRUS-guided system. After creation of a three-dimensional map of the prostate, a computer algorithm identified an ideal biopsy scheme based on the measured dimensions of the prostate. The system then used a fixed template that allowed prostate biopsy at specific locations with the ability to target the same region of the prostate in the future if needed. For all patients, a 12-core biopsy pattern was used to cover medial and lateral areas of the base, mid-gland, and apex. In total, 68 patients underwent 3-D TRUS-guided prostate biopsies between April 2006 and November 2007 for prostate cancer detection. The indication for prostate biopsy was PSA > or = 4.0 ng/ml in 47 (69%) patients, abnormal digital rectal examination (DRE) in 17 (25%), and atypia on previous biopsy in 4 (6%) patients. Prostate cancer was detected in 18 patients (26.5%) and 7 (10.3%) had atypical small acinar proliferation (ASAP). The highest frequency (55.5%) from all cases of cancer detected was identified when 3-D TRUS biopsy was used as the initial biopsy. This study demonstrates that a 3-D TRUS-guided biopsy system translates to a more frequent detection of prostate cancer among patients undergoing an initial prostate biopsy than a subsequent one. More comprehensive studies are warranted to corroborate and extend the results of this study.

Utilization of (111)In-Capromab pendetide SPECT-CT for detecting seminal vesicle invasion with recurrent prostate cancer after primary in situ therapy.

The aim of this study was to evaluate the diagnostic value of a hybrid (111)In-capromab pendetide fused computed tomography (CT) scan in detecting seminal vesicle invasion (SVI) in the setting of recurrent prostate cancer following primary in situ therapy. The study population comprised 59 patients, who biochemically failed primary in situ treatment based on American Society for Therapeutic Radiology and Oncology criteria. The patients underwent an (111)In-capromab pendetide/CT scan at the time of biochemical failure with a prostate (12-core) and seminal vesicle (SV) (8-core) biopsy. The diagnostic properties of the scan and magnetic resonance imaging (MRI) in detecting SVI compared to an SV biopsy were calculated. In total, eight (14%) patients had a positive SV biopsy after primary in situ prostate cancer treatment. Nine (15%) patients had positive uptake of the scan in the SV. When comparing the SV scan results to the SV biopsy, the sensitivity, specificity, positive predictive value, and negative predictive value were 37.5%, 88.2%, 33.3%, and 90.0% (95% confidence interval: 0.44-0.81), respectively. In contrast, the ability of MRI to detect SVI was 50.0%, 81.3%, 40.0%, and 86.7% (95% confidence interval: 0.46-0.85), respectively. Although the sensitivity and positive predictive value of the (111)In-capromab pendetide/CT scan are low, its specificity and negative predictive value are high. Based on these findings, the ability of the (111)In-capromab pendetide/CT scan to detect SVI seems to be comparable with MRI.

Altered male physiologic function after surgery for prostate cancer: couple perspective.

PURPOSE: Both the diagnosis of prostate cancer (PCa) and the physiologic outcomes of surgical treatment impact the male's psychological sphere. However, current research advocates a refocusing of outcomes directed to the PCa "couple". Herein we acquire insight into perspective and concordance regarding male physiological function from the standpoint of a couple recovering from PCa surgery. MATERIALS AND METHODS: Couples whereby the male partner had undergone primary surgical treatment for PCa were mailed a Retrospective Sexual Survey (RSS) packet consisting of male and female partner questionnaires. RSS questions surveyed physiological changes in libido, foreplay, erection and arousal, orgasm and ejaculation in addition to perceived psychological impact. Patients' and partners' scores were evaluated to determine the concordance of both individual items as well as domain sums. RESULTS: Twenty-eight couples completed the questionnaires. Only about 40% of men and women were happy with their levels of sexual interest with 82% concordance. Urine loss during orgasm was reported by 43% of men; the majority of participants were bothered by it. Ejaculation changes were observed by 96% of men (concordance 96%) with most reporting anejaculation. A change in orgasm experience was noted by 86% of men (and 36% of their female partners, p < 0.0001). Despite the change, the majority of men and women reported being satisfied with their ability to climax. CONCLUSION: Our results indicate that patients and their female partners may interpret differently the same physiological outcomes of PCa surgery. This information could be useful to better counsel the PCa couple and help patients and partners adjust after surgery.

Pathologic stage T2a and T2b prostate cancer in the recent prostate-specific antigen era: implications for unilateral ablative therapy.

BACKGROUND: Early detection of small volume prostate cancer (PCa) has led to the concept of focal therapy to treat in an organ-sparing manner. We evaluated trends in pathologic staging among patients with localized PCa undergoing radical prostatectomy (RP), defining the frequency of unilateral cancers during 1988-1995, 1996-2000 and 2001-2006. METHODS: Data were abstracted from the Duke Prostate Cancer Outcome database selecting 3,676 men with available pathology treated with RP. Based on surgical pathology, trends in as pathological T (pT) stage, pathological Gleason Score (pGS), and percent tumor involvement (PTI) were evaluated. RESULTS: pT2a increased from 2.8% of men undergoing RP in 1988-1995 to 13.0% during 2001-2006 (P < 0.0005). PTI analysis shifted towards low volume disease, e.g. PTI

From whole-gland to targeted cryoablation for the treatment of unilateral or focal prostate cancer.

The intermediate and long-term results of primary full-gland cryoablation for localized prostate cancer with moderate- and high-risk patients suggests a cancer control rate similar to what can be achieved with radiotherapy and surgery, with an acceptable rate of complications. A recent shift in the treatment paradigm toward unilateral cryoablation (hemiablation) or ablation of unifocal lesion(s) in select patients suggests the ability of this approach to maintain a quality of life closer to the pretreatment level. However, trials with longer oncologic follow-up are needed. The development of more accurate imaging-based techniques-ie, image-guided prostate biopsy sampling and image-guided prostate cryoablation-is of paramount importance to selecting appropriate candidates for an organ-sparing procedure. To make this approach scientifically sound, further investigation to establish patient selection criteria, the development of molecular and imaging parameters of cryoablative efficacy, and regular careful follow-up of these patients is needed.

Impact of a cryotherapy training workshop on the adoption and utilization of cryotherapy in the community setting.

INTRODUCTION: Given the improved therapeutic efficacy and acceptable side effect profile with current cryotechnology, we wish to better understand the attitudes of community urologists expressing interest in this treatment modality toward the adoption of cryotherapy in their practice. METHODS: A retrospective survey was conducted with information gathered on 50 responding physicians who attended a cryosurgery workshop between February 2004 and September 2006. Specifics such as demographics and professional background, reasons for interest in cryosurgery, and the current status of cryosurgery in the physicians' practice were collected and analyzed using SPSS, version 14 (Chicago, IL). RESULTS: Of the responding 50 physicians who attended a cryotherapy training workshop, 33 (66%) had been in practice for >/= 15 years. The most frequently cited reasons for interest in cryosurgery were the intention to introduce cryosurgery into routine practice for treatment of primary (70%) and salvage (62%) prostate cancer and treatment of renal neoplasms (62%). Most physicians reported the learning curve to be short. Of the 22 (44%) physicians currently practicing cryotherapy, most are using the technique for treatment of primary prostate cancer and as a salvage procedure for radiorecurrent prostate cancer. Twenty-eight (56%) physicians reported that they were not practicing cryosurgery yet, mainly citing lack of patient interest/appropriate patients and/or a lack of institutional support. CONCLUSIONS: This study provides insight into the attitudes of community urologists to adopt cryotherapy into their practice following a training course. Although some surgeons successfully integrate cryotherapy into their practice, further efforts must be made to remove barriers to allow adoption of this technology in the community setting.

Analysis of laterality and percentage of tumor involvement in 1386 prostatectomized specimens for selection of unilateral focal cryotherapy.

In total, 1386 paraffin embedded radical prostatectomy specimens from patients with clinically localized prostate cancer (PCa) excised between 2002-06 were analyzed. Pathologic assessment paid particular attention to laterality and percentage of tumor involvement (PTI) along with pathologic Gleason Score (pGS). Completely unilateral cancers were identified in 254 (18.3%) patients, and in 39% cases of them the signs of clinically significant PCa were revealed. The majority of unilateral tumors (72%) were low volume with a PTI of < or =5. This study suggests that only a select group of men diagnosed with PCa have completely unilateral cancers that would be amenable to focal ablation therapy targeting 1 lobe. Further study is needed to develop predictive models for those patients likely to have small, unilateral cancers that may be amenable to focal therapy.

Prostatic abscess as a delayed complication following cryosurgery for primary prostate cancer.

Prostatic abscess is a rare and potentially life-threatening disease when left untreated. We report the first case of a man who developed a prostatic abscess as a long-term complication of cryoablation for primary prostate cancer. Timely diagnosis with non-contrast computed tomography (CT) scan, retrograde CT cystogram to ensure no bladder involvement, percutaneous drainage under CT-guidance, and antibiotic treatment sensitive to the causative organism were crucial for prompt recovery.

Can the conventional sextant prostate biopsy accurately predict unilateral prostate cancer in low-risk, localized, prostate cancer?

We evaluate the reliability of routine sextant prostate biopsy to detect unilateral lesions. A total of 365 men with complete records including all clinical and pathologic variables who underwent a preoperative sextant biopsy and subsequent radical prostatectomy (RP) for clinically localized prostate cancer at our medical center between January 1996 and December 2006 were identified. When the sextant biopsy detects unilateral disease, according to RP results, the NPV is high (91%) with a low false negative rate (9%). However, the sextant biopsy has a PPV of 28% with a high false positive rate (72%). Therefore, a routine sextant prostate biopsy cannot provide reliable, accurate information about the unilaterality of tumor lesion(s).

Tumor size and endophytic growth pattern affect recurrence rates after laparoscopic renal cryoablation.

OBJECTIVE: To analyze factors that may contribute to local relapse after laparoscopic cryoablation (LCA) of renal tumors. LCA has gained popularity in the treatment of small renal tumors, but local tumor control remains a concern. METHODS: We analyzed 163 patients who underwent LCA between 2001 and 2008 either at Allegheny General Hospital or Duke University Medical Center, with at least 6 months of follow-up. Demographics, perioperative variables, tumor characteristics (size, pattern of growth, and biopsy results), and follow-up were recorded. Growth pattern was categorized as exophytic, mesophytic, or endophytic. Regression analyses were performed to evaluate risk factors for local relapse after LCA. RESULTS: Median patient age was 66 (range, 33-90) years, with men comprising 60.1% of the cohort. Median tumor size was 2.4 cm (range, 0.5-5.0). Pathology was as follows: renal cell carcinoma in 118 (72.4%), other malignancies in 2 (1.2%), and no malignancy in 43 (26.4%) patients. A single lesion was treated in 95.1% patients and multiple tumors in 4.9%. Endophytic growth pattern was present in 22.8% patients. We observed 7 (4.3%) local recurrences over a median follow-up of 20 months (range, 6-79). Median time to recurrence was 15 months (range, 6-48). On proportional hazards regression, tumor size and endophytic growth pattern were significantly associated with local recurrence (P = .003 and .028; odds ratios [OR] = 4.1 and 11.4, respectively). CONCLUSIONS: LCA demonstrated good tumor control over a 5-year follow-up, with an acceptable recurrence rate. Larger tumors and those with endophytic growth pattern may be at increased risk of relapse after LCA.

Analysis of urinary function using validated instruments and uroflowmetry after primary and salvage prostate cryoablation.

OBJECTIVES: To evaluate changes in urinary function after cryoablation for clinically localized prostate cancer and to investigate risk factors that predict changes in urinary function after surgery. METHODS: Among the patients who underwent primary or salvage cryoablation between January 2002 and May 2008, 74 patients (50 primary and 24 salvage) with both a preoperative and postoperative urinary function domain score and uroflowmetry were included in this study. The mean age was 66.8 ± 7.5 years and the mean follow-up period was 42.5 ± 20.3 months. The changes in postoperative urinary function were evaluated on the basis of several categorized groups, including surgical method, preoperative urinary symptoms, and prostate volume. RESULTS: Of 74 patients, 2 (2.7%) presented with mild stress incontinence after cryoablation. No patient presented with persistent urinary retention or urethral fistula. When comparing postoperative International Prostate Symptom Score (IPSS) and bother index scores with preoperative scores, it was found that on average IPSS and bother index recovered 12 and 18 months after cryoablation, respectively, and continued to improve after recovery. Only salvage cryoablation correlated with deteriorating urinary function in a logistic regression model (P = .032). However, it was noted that the patients with preoperative moderate to severe urinary symptoms and larger prostate volume showed improvement of urinary function after cryoablation. No associations were found between worsened urinary function and prostate volume, comorbidities (hypertension, obesity, and diabetes), or sexual function. CONCLUSIONS: Cryoablation is a minimally invasive surgery for localized prostate cancer. This study is the first to demonstrate the ability of cryoablation in terms of maintaining and potentially improving urinary function using validated instruments and uroflowmetry assessments.

Pathologic basis of focal therapy for early-stage prostate cancer.

The treatment paradigm for small-volume, low-grade unifocal or unilateral prostate cancer is shifting from a radical, whole-gland approach toward organ-sparing, focal ablation. The widely implemented screening program in the US has detected small-volume prostate lesions at early stages of carcinogenesis, which has enabled the shift in treatment paradigm. An image-guided approach to focal therapy has yet to be realized, and is dependent on the development of an imaging modality that detects cancer with high sensitivity and specificity. The future success of focal therapy will depend on adequate prostate sampling at biopsy, along with accurate characterization of the spatial distribution of tumor within the prostate. The pathologic evaluation of radical prostatectomy specimens remains of paramount importance, as this reference standard can validate all preoperative clinical, demographic, laboratory, imaging and prostate biopsy findings.

Patient selection for hemiablative focal therapy of prostate cancer: variables predictive of tumor unilaterality based upon radical prostatectomy.

BACKGROUND: The application of focal therapy for low-risk prostate cancer (PCa) depended on appropriate patient selection. No definitive criteria existed to characterize patients who may potentially benefit from an organ-sparing approach. We evaluated pretreatment clinical parameters that may predict unilateral PCa amenable to hemigland thermoablation. METHODS: In total, 538 patients with complete data from the Duke Prostate Center (DPC) Outcomes database with low- to low-intermediate-risk PCa (prostate-specific antigen<10 ng/mL, biopsy Gleason score < or =7, and clinical stage T1c-T2b) treated with radical prostatectomy (RP) were included in the dataset. Patients underwent diagnostic prostate biopsy (PBx) at Duke or community hospitals from 1996 to 2006. Clinical and biopsy parameters were assessed as to the ability to predict PCa unilaterality verified by RP pathology. RESULTS: The strongest predictor of pathologic unilaterality was PBx unilaterality. The sensitivity and specificity for biopsy unilaterality to predict pathologic unilaterality was 88.4% and 34%, with a positive predictive value of 28% and a negative predictive value of 91%. PBx unilaterality (odds ratio [OR] = 3.88; 95% confidence interval [CI], 2.14-7.05; P < .0005) and negative family history of PCa (OR = 1.83; 95% CI, 1.09-3.05; P = .21) was associated with a higher probability of unilateral disease by multivariate regression. CONCLUSIONS: Two pretreatment clinical variables were significantly predictive of unilateral PCa: negative family history of PCa and PBx unilaterality. These variables may be used to select men with low- to low-moderate-risk PCa for hemiablation. Further work is necessary to decrease the false-negative and false-positive rates associated with PBx to improve predictability for PCa laterality.

Changes in Gleason score grading and their effect in predicting outcome after radical prostatectomy.

OBJECTIVES: To compare Gleason scores (GS) originally assigned in the mid 1990s with the current pathologic evaluation of the same prostatectomy slides, and to assess the GS migration effect on outcome in patients undergoing surgical treatment of prostate cancer. METHODS: We reviewed medical charts of consecutive patients who underwent a radical prostatectomy for T2-T3 prostate cancer at our Medical Center between 1995 and 1997. Prostate specimen slides of 204 patients were reviewed and GS was reassigned in a blinded fashion by a single uropathologist in 2008. GS distributions were compared, and original and re-evaluated GS were assessed for predictive ability in survival regression models. RESULTS: GS distribution differed significantly between the mid 1990s and the current evaluation (P < .001), with the average reevaluated GS higher than the initial one (6.14 vs 6.39, P < .001). The GS was upgraded in 63 cases (30.9%) and downgraded in 25 (12.3%) at reevaluation. The initial GS was predictive (P = .002) of prostate-specific antigen recurrence (PSAR), whereas the newly assigned GS was not (P = .393). However, grouping reassigned GS into risk groups (low < 7, moderate = 7 and high > 7) yielded a better PSAR definition. Survival curves of initial GS could not distinguish between moderate- and high-risk groups, although reassigned GS curves showed statistically significant differences between all risk groups. CONCLUSIONS: These results suggest that interpretation of pathologists played a significant role in the GS shift and propose that the contemporary GS remains a useful prognostic factor of PSAR when stratified in risk categories, although the single GS value may not be as important.

Urothelial sloughing with obstruction after laparoscopic cryoablation of small renal carcinoma in solitary kidney.

Laparoscopic cryoablation is a minimally invasive treatment that is currently used to treat small renal tumors. Despite its growing use and promising outcomes, complications can occur. We report the first clinical case of urothelial sloughing with obstruction after cryoablation of a small renal tumor in a solitary kidney.

Persistent contrast enhancement several months after laparoscopic cryoablation of the small renal mass may not indicate recurrent tumor.

PURPOSE: We evaluated the clinical implication of persistent contrast enhancement demonstrated several months after laparoscopic renal cryoablation of a small renal mass. PATIENTS AND METHODS: Between September 2000 and May 2007, 30 patients underwent laparoscopic cryosurgery for an organ-confined renal tumor measuring