Janice M. Mayes

Prostate cancer laterality as a rationale of focal ablative therapy for the treatment of clinically localized prostate cancer

Early detection of small‐volume prostate cancer (PCa) has led to the concept of focal therapy to treat PCa as an organ‐sparing, minimally invasive procedure. The authors sought to determine the frequency of unilateral cancers in the contemporary prostate‐specific antigen (PSA) era to determine the percentage of patients who would be candidates for hemiablation of the prostate by using focal therapy while preserving the contralateral lobe.

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.

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

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.

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.

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.

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

Study Type – Diagnosis (exploratory cohort)
Level of Evidence 2b

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 ≤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.

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.

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.