Do all patients with high‐grade prostatic intraepithelial neoplasia on initial prostatic biopsy eventually progress to clinical prostate cancer?

OBJECTIVE: To assess the clinical outcome of patients with a diagnosis of high-grade prostatic intraepithelial neoplasia (PIN) on initial prostatic biopsy, with a minimum of 5 years of follow-up, as such patients are at greater risk of having prostate cancer on subsequent biopsy. PATIENTS AND METHODS: Between November 1992 and October 1998, 21 patients were identified as having PIN on their initial transrectal ultrasonography-guided prostate biopsy. None of these patients had a focus of cancer on the initial biopsy. Their medical data were reviewed retrospectively to determine the natural history of PIN in these patients. Patients who were not identified as having cancer were followed every 6-12 months with prostate-specific antigen (PSA) testing and digital rectal examinations (DRE). RESULTS: A mean (range) of 7 (2-8) cores were taken at initial biopsy; the mean age of the patients was 63 (53-77) years and mean PSA level 9.1 (4.9-17.6) ng/mL. Six patients had an abnormal DRE at presentation. A mean of 8 (7-10) cores were obtained on the second biopsy; six patients were diagnosed with cancer, with a mean Gleason score of 6 (5-7), while three were diagnosed with persistent PIN. These three patients had a third prostate biopsy which showed cancer of Gleason score 6 in one and benign prostatic hyperplasia in two. After a mean follow-up of 72.2 (60-84) months, none of the remaining 12 patients was diagnosed with clinically significant cancer. Five of these patients went on to a third prostate biopsy, with no evidence of cancer. One patient died from unrelated causes during this period. CONCLUSION: This study affirms our current practice of following patients with PIN conservatively if a second or third subsequent prostate biopsy is negative. Whether PIN is a premalignant lesion or merely a lesion associated with cancer needs to be addressed in multicentre studies with a follow-up of > 10 years.     

Prognostic factors and outcome in patients with T1 high‐grade bladder cancer: can we identify patients for early cystectomy?

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Although several papers have attempted to identify individual risk factors for T1 high‐grade (T1HG) urothelial carcinoma of the bladder for disease recurrence or progression, and nomograms have been generated to aid in the prediction of disease progression, there has been a lack of systematic examination of which factors predict clinically important outcomes. Treatment of T1HG remains controversial, particularly with regards to timing of radical cystectomy. Patients with T1HG bladder cancer are at a significant risk of progression and death from disease. Primary tumours, sessile architecture, and trigonal location are factors associated with worse outcome and may be used to counsel patients towards early cystectomy.

OBJECTIVE

• ? To assess outcome in patients with T1 high‐grade (T1HG) bladder cancer treated at a single academic institution and to determine the prognostic factors that can help in counselling patients towards early cystectomy.

PATIENTS AND METHODS

• ? Records of 2570 patients with bladder cancer treated from 1995 to 2005 were reviewed. Only patients diagnosed with T1HG disease were included in the analysis.
• ? Collected variables included various clinicopathological parameters, use of statins, smoking, as well as dates of recurrence, progression, radical cystectomy and death.
• ? Recurrence‐free survival (RFS) and worsening‐free survival (WFS) were analyzed.
• ? Multivariate Cox proportional regression analysis was employed to verify the prognostic significance of various variables.

RESULTS

• ? In total, 278 (10.8%) patients were identified as having T1HG disease on transurethral resection.
• ? 66% of patients who recurred, and 36.3% developed stage progression after a median (range) follow‐up of 3 (0.1–15.4) years.
• ? 30% patients who underwent radical cystectomy, and 9% were dead of disease.
• ? The 5‐year RFS and WFS rates were 26.6% and 49.4%, respectively.
• ? On multivariate analysis, only non‐trigonal tumour location, restaging transurethral resection, history of previous carcinoma not invading bladder muscle and adjuvant bacille Calmette‐Guérin (BCG) therapy were significantly associated with prolonged RFS, whereas papillary tumour architecture, history of previous carcinoma not invading bladder muscle and adjuvant BCG therapy were significantly associated with prolonged WFS.

CONCLUSIONS

• ? Patients with T1HG bladder cancer are at a significant risk of progression and death from disease.
• ? Primary tumours, sessile architecture and trigonal location are factors associated with a worse outcome and may be used to counsel patients towards early cystectomy.

     

Do all patients with bilateral testis cancer have a hereditary predisposition?

An international study has demonstrated that patients with bilateral testicular cancer are significantly more likely to have brothers with testis cancer than those with unilateral disease. This, together with other evidence, implies that patients with bilateral disease are likely to carry a predisposing genotype. But is it the great majority of them which is thus predisposed? We show that if as few as half of these patients have the predisposing genotype, its penetrance would have to be 80%, causing 38% of resulting cases to be bilateral. Evidence from the International Testis Cancer Linkage Consortium shows that the proportion of familial cases with bilateral disease is much lower. It is likely that at least the majority of cases of bilateral testis cancer arise as a result of a predisposing genotype.     

Atrophy in specimens of radical prostatectomy: is there topographic relation to high-grade prostatic intraepithelial neoplasia or cancer?

Introduction  

It is controversial whether there is any relationship of proliferative inflammatory atrophy (PIA) to high-grade prostatic intraepithelial neoplasia (HGPIN) and cancer (CA). It has been suggested a topographic relation and a potential of the proliferative epithelium in PIA to progress to HGPIN and/or CA. The aim of this study was to analyze in radical prostatectomies a possible topographic relation of the lesions.     

Does repeat biopsy affect the prognosis of patients with prostate cancer treated with radical prostatectomy? Analysis by the number of cores taken at initial biopsy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? To date, studies to evaluate clinical significance of prostate cancer detected on repeat biopsy in patients who underwent radical prostatectomy have yielded inconsistent results. The present study confirms that prostate cancer diagnosed after repeat biopsies is related to better pathological outcomes after radical prostatectomy, but not predictive of biochemical recurrence. Additionally, we find that the number of cores taken at initial biopsy do not affect the association between the number of previous biopsies and the prognosis.

OBJECTIVE

• ? To determine whether repeat prostate biopsies are associated with more favourable prognoses compared with diagnosis at initial biopsy in patients who undergo radical prostatectomy for prostate cancer and to determine if this association is affected by the number of cores taken at initial biopsy.

PATIENTS AND METHODS

• ? We reviewed 1147 patients with prostate cancer from 1991 to 2008.
• ? Patients were stratified into two groups by the number of biopsies before diagnosis (initial biopsy vs repeat biopsy: at least two biopsies).
• ? The effects of several variables on pathological outcomes and biochemical recurrence‐free and systemic progression‐free survivals were assessed.

RESULTS

• ? Of the 1147 patients, 1064 (92.8%) were diagnosed with cancer at first biopsy and 83 (7.2%) at repeat biopsy.
• ? Compared with patients diagnosed at initial biopsy, those diagnosed at repeat biopsies were more likely to have a lower clinical stage (cT1c: 79.5% vs 55.5%, P < 0.001) and organ‐confined tumours (78.3% vs 61.3%, P= 0.003), but there was no significant difference in initial biopsy core number (8.3 vs 8.7, P= 0.373).
• ? Five‐year biochemical recurrence‐free and progression‐free survival rates did not show significant differences between the two groups (88.8% vs 82.2%, P= 0.078; 100.0% vs 96.5%, P= 0.105, respectively), and these results were not affected by the number of cores taken at initial biopsy.

CONCLUSIONS

• ? Although prostate cancer diagnosed after repeat biopsies was related to better pathological outcomes after radical prostatectomy, the number of previous biopsies did not predict disease recurrence.
• ? Moreover, the number of cores taken at initial biopsy did not affect these associations.

     

Is intermittent androgen‐deprivation therapy beneficial for patients with advanced prostate cancer?

Use of intermittent androgen‐deprivation therapy (IADT) in patients with prostate cancer has been evaluated in several studies, in an attempt to delay the development of castration resistance and reduce side‐effects associated with ADT. However it is still not clear whether survival is adversely affected in patients treated with IADT. In this review, we explore the available data in an attempt to identify the most suitable candidate patients for IADT, and discuss factors that may inform appropriate patient stratification. ADT is first‐line treatment for advanced/metastatic prostate cancer and is also recommended for use with definitive radiotherapy for high‐risk localised prostate cancer. The changes in hormone levels induced by ADT can lead to short‐ and long‐term side‐effects which, although treatable in most cases, can significantly reduce the tolerability of ADT treatment. IADT has been investigated in several phase II and phase III studies in patients with locally advanced or metastatic prostate cancer, in an attempt to delay time to tumour progression and reduce the side‐effect burden of ADT. In selected patient groups IADT is no less effective than continuous ADT, ameliorating the impact of ADT‐related side‐effects, and, to a degree, their impact on patient health‐related quality of life (HRQL). Further comparative study is required, particularly in relation to HRQL and long‐term complications associated with ADT.     

Should all postmenopausal patients with hormone receptor-positive breast cancer receive initial therapy with aromatase inhibitors?

BackgroundIn the past few years aromatase inhibitors (AIs) have shown superior efficacy to the previous standard adjuvant endocrine therapy, tamoxifen, and are now recommended as part of current adjuvant endocrine therapy. A range of treatment strategies have been explored.Materials and methodsWe assess the role of initial AI therapy for postmenopausal women with hormone receptor-positive breast cancer and consider the relative value of initial therapy with an AI compared with switch or extended (>5-yr) adjuvant therapy.ResultsBoth initial AI therapy and switching/sequential tamoxifen followed by an AI are associated with longer disease- and relapse-free survival versus 5 years of tamoxifen alone. Trials comparing initial therapy with the sequence of tamoxifen followed by an AI have not demonstrated any major efficacy differences between the treatment strategies. Several analyses have been conducted to identify prognostic or predictive markers of treatment benefit to enable selection of the most appropriate adjuvant therapy.ConclusionsInitial and switching/sequential regimens are equally appropriate adjuvant treatment options for postmenopausal patients with hormone receptor-positive breast cancer. The exact tumour biology which allows for initial AI therapy has not yet been determined with certainty.     

How much does Gleason grade of follow‐up biopsy differ from that of initial biopsy in untreated,Gleason score 4–7, clinically localized prostate cancer?

OBJECTIVE: To compare histologic grades between an initial biopsy and a follow-up biopsy in untreated, Gleason score (GS) 4-7, clinically localized prostate cancer. METHODS AND MATERIALS: In a prospective single-arm cohort study, clinically localized, GS 4-7, prostate cancer was managed with active surveillance alone, provided that a pre-defined definition of disease progression was not met. One hundred five (63%) of a total of 168 eligible patients underwent a follow-up prostate biopsy during surveillance. Median time to a follow-up biopsy was 22 months (range: 7-81). Histologic grades between these two biopsies were compared to evaluate the extent of histologic grade change. RESULTS: On the follow-up biopsy, GS was unchanged in 33 patients (31%), upgraded in 37 (35%), and downgraded in 34 (32%). Eleven (10%) had upgrading by 2 Gleason points or more. Eight (8%) had upgrading to GS 8 (none to GS 9 or 10); of these, six were among those with upgrading by 2 Gleason points or more. Twenty-seven (26%) had no malignancy on the follow-up biopsy. Negative follow-up biopsy was more prevalent in patients with a small volume of malignancy in the initial biopsy and a low baseline PSA. CONCLUSIONS: No consistent change in histologic grade was observed on the follow-up biopsy at a median of 22 months in untreated, GS 4-7, clinically localized prostate cancer. Upgrading to GS > or =8 or by 2 Gleason points or more was relatively uncommon.     

Do men with prostate abnormalities (prostatitis/benign prostatic hyperplasia/prostate cancer) develop immunity to spermatozoa or seminal plasma?

Prostate is an immunocompetent and not an immunoprivileged organ. It has an active immunologic armamentarium. There are three major prostate abnormalities namely, prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer. In all these abnormalities, infection/inflammation has been implicated. As infection/inflammation of the male genital tract can also be involved in induction of antisperm antibodies (ASA), this study was conducted to examine if these prostate abnormalities lead to the formation of ASA. Sera were obtained from normal healthy men (n = 20), men with chronic prostatitis (n = 20), men with BPH (n = 25), men with prostate cancer (n = 25) and immunoinfertile men (n = 10). The presence of antisperm antibodies against lithium diiodosalicylate (LIS)-solubilized human sperm extract (HSE), seminal plasma and synthetic peptides based upon sperm-specific antigens namely fertilization antigen (FA-1) and YLP(12), were analysed using the sperm immobilization technique (SIT), tray agglutination technique (TAT), enzyme-linked immunosorbent assay (ELISA) and indirect immunobead binding technique (IBT). All the sera from normal men and men with prostate abnormalities (chronic prostatitis/BPH/prostate cancer) were found to be negative in SIT and TAT. In ELISA, a few sera from men having prostate abnormalities (4-24%) showed a weak positive immunoreactivity (2-3 SD units) with some of the spermatozoa/seminal plasma antigens. Majority of the samples did not show any immunoreactivity (<2 SD units) in ELISA. Even the samples that showed a weak positive immunoreactivity in ELISA did not bind to live human sperm in IBT, indicating lack of sperm binding antibodies in these sera. In all these assays, the sera from immunoinfertile men were positive. Our findings indicate that chronic prostatitis, BPH and prostate cancer do not induce antibodies to spermatozoa, sperm-specific antigens and seminal plasma components. Although prostate is an immunologically competent organ, and its abnormalities cause a rise in circulating prostate-specific antigen (PSA), it appears that there is no concomitant induction of immunity to spermatozoa/seminal components including sperm-specific fertility-related antigens, thus not causing ASA-induced immunoinfertlity. This is the first study to our knowledge reporting the absence of ASA in men with BPH and prostate cancer.     

Family history? The forgotten question in high‐risk colorectal cancer patients

Aim  The aim of the study was to investigate the frequency and detail of family history recorded for patients diagnosed with potentially high-risk colorectal cancer, and to determine the proportion of these patients referred to a high-risk assessment clinic.
Method  Medical records of patients diagnosed with colorectal cancer under the age of 50 admitted to a major Sydney teaching hospital were reviewed. The proportion of records containing information about family history was calculated. Associations between recording of family history and demographic and clinical characteristics of patients were investigated. Logistic regression modelling was performed to identify significant, independent predictors of study outcomes.
Results  Of 113 patients with colorectal cancer diagnosed under the age of 50 years, 61 (54%, 95% CI: 44–63%) had an entry in their hospital medical record about family history. Family history was significantly less likely to be recorded for females, for those admitted via the Emergency Department, and for those with shorter lengths of stay. A significant family history was found in 51% of the 61 patients who had a family history recorded. Records of patients attending specialist colorectal surgeons were significantly more likely to contain information about family history than those who attended other specialists ( P  = 0.04). Only 14 patients (12%, 95% CI: 7–20%) were formally referred for further genetic assessment.
Conclusion  These results suggest that family history is still being neglected in routine clinical practice, and high-risk assessment services are underutilized, implying the need for further dissemination of guidelines with regard to the recognition and management of hereditary colorectal cancer.     

Is excisional biopsy indicated for patients with lobular neoplasia diagnosed on percutaneous core needle biopsy of the breast?

Background

The value of excisional biopsy for patients with lobular neoplasia diagnosed by core needle breast biopsy is controversial.

Methods

A retrospective analysis of all patients with lobular carcinoma in situ or atypical lobular hyperplasia on core needle biopsy.

Results

Twenty-five patients were identified. Twelve (48%) underwent excisional biopsy. None of the patients who had excisional biopsy were found to have ductal carcinoma in situ (DCIS) or invasive cancer. The mean follow-up was 66 months. Five patients (20%) developed DCIS or invasive cancer during follow-up. The rate of subsequent carcinoma among those undergoing excisional biopsy was 25%, and among those not undergoing excisional biopsy it was 15% (P = .57). Among patients who did not undergo excisional biopsy, none developed carcinoma within the same quadrant of the breast.

Conclusions

Excisional biopsy for lobular neoplasia did not identify understaged carcinoma or alter the rate of subsequent carcinoma. The subsequent carcinoma risk is diffuse and bilateral; it does not correlate with the site at which lobular neoplasia was diagnosed.