Final outcomes of patients with low‐risk prostate cancer suitable for active surveillance but treated surgically

OBJECTIVE

To study the outcomes of a contemporary cohort of patients referred from around the UK with low‐risk prostate cancer consistent with the UK National Institute for Health and Clinical Excellence guidelines for active surveillance but who were treated with laparoscopic radical prostatectomy (LRP) in a single surgeon series.

PATIENTS AND METHODS

From 1080 consecutive patients who underwent LRP between March 2000 and April 2008, 549 patients (51%) had low preoperative risk disease (PSA level <10 ng/mL, clinical stage ≤T2a and biopsy Gleason score ≤6). The pathological outcomes of these 549 patients as well as a subgroup of 74 patients with preoperative prediction of ‘insignificant’ disease were assessed.

RESULTS

The mean age of the patients was 61 years, the mean (range) PSA level was 6.1 (1–9) ng/mL; 38% of patients were staged as cT2a. In all, 126 patients (23%) were upgraded on final pathology to Gleason score ≥7. In all, 29 patients (5%) had extraprostatic extension with seminal vesicle invasion in five (0.9%). Of the 74 patients with preoperative prediction of insignificant disease, 61% had significant disease with 16% upgraded to an intermediate‐risk group. Overall, there were positive margins in 44 patients (8.0%) and biochemical failure occurred in six patients (1.1%) with a median follow‐up of 28 months.

CONCLUSION

In this contemporary UK cohort of patients with apparently low‐ or favourable‐risk prostate cancer, 23% will have higher grade disease than preoperatively predicted. Even though active surveillance is increasingly being recommended for managing low‐risk localized prostate cancer, patients and their physicians need to be aware of the potential for harbouring more significant disease.     

Population‐based prostate‐specific antigen testing in the UK leads to a stage migration of prostate cancer

OBJECTIVE

To determine, within the UK, the stage and grade of prostate cancers that would be found through population‐based prostate specific antigen (PSA) testing and biopsy.

SUBJECTS AND METHODS

In the ‘Prostate Testing for Cancer and Treatment’ trial (ProtecT), men aged 50–69 years were recruited from nine cities in the UK and from randomly selected practices of general practitioners. Those with a PSA level of >3 ng/mL were offered a prostate biopsy. Age, PSA, stage and grade at diagnosis of ProtecT participants with cancer were compared with contemporaneous incident cases aged 50–69 years (age‐restricted Cancer Registry cases) registered with the Eastern Cancer Registration and Information Centre (ECRIC).

RESULTS

Within ProtecT, 94 427 men agreed to be tested (50% of men contacted), 8807 (≈9%) had a raised PSA level and 2022 (23%) had prostate cancer; 229 (≈12%) had locally advanced (T3 or T4) or metastatic cancers, the rest having clinically localized (T1c or T2) disease. Within ECRIC, 12 661 cancers were recorded over the same period; 3714 were men aged 50–69 years at diagnosis. Men in ProtecT had a lower age distribution and PSA level, and the cancers were of lower stage and grade (P < 0.001 for all comparisons). If population‐based PSA testing were introduced in the UK, ≈2660 men per 100 000 aged 50–69 years would be found to have prostate cancer, compared to current rates of ≈130 per 100 000. If half of men accepted PSA testing, ≈160 000 cancers would be found, compared to 30 000 diagnosed each year at present.

CONCLUSIONS

Population‐based PSA testing resulted in a significant downward stage and grade migration, and most such cancers were of low stage and grade, which could lead to risks of over‐treatment for some men.     

Trends in the treatment of localized prostate cancer using supplemented cancer registry data

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Variation in treatment of localized prostate cancer has been shown to exist according to demographic and clinical factors, patient and provider preference, and region of residence since there is no consensus concerning appropriate treatment. Between 1998 and 2002 the proportion of men choosing watchful waiting declined from 12.6% to 9.0% while those receiving brachytherapy (with or without external beam radiation therapy) increased from 14.9% to 17.7%. Based on Gleason score, PSA, and age at diagnosis, younger African‐American men may be receiving less aggressive therapy than indicated, while older men with low risk tumours may be receiving more aggressive therapy than necessary.

OBJECTIVE

To conduct an analysis of localized prostate cancer treatment in the USA between 1998 and 2002.

PATIENTS AND METHODS

Results from the National Cancer Institute’s Patterns of Care study from 10 regional cancer registries in 1998 and 14 registries in 2002 were compared using univariate and multivariate statistical methods.

RESULTS

Patients with localized prostate cancer in 2002 were younger, had lower prostate‐specific antigen values, and higher Gleason scores compared with those diagnosed in 1998. Little change occurred in age‐adjusted percentages of men who were treated with a radical prostatectomy (45–46%) or by external beam radiation (EBRT) alone (19–20%). The proportion receiving brachytherapy (BT), alone or with EBRT, increased from 14.9 to 17.7%, while the proportion receiving watchful waiting declined from 12.6 to 9.0%. Younger African‐American men with intermediate/high‐risk disease were less likely to receive any type of aggressive therapy in comparison with Non‐Hispanic White men. Over 70% of men who were ≥75 years of age, with low‐risk disease, were treated with EBRT or BT.

CONCLUSIONS

Older men with low‐risk disease might be overtreated with aggressive therapy, while younger intermediate/high‐risk African‐American men appear less likely to receive indicated aggressive therapy.     

Prostate‐specific antigen relapse‐free survival and side‐effects in 734 patients with up to 10 years of follow‐up with localized prostate cancer treated by permanent 125iodine implants

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To report our analysis of the oncological outcome, side‐effects and complications after ¹²⁵I‐brachytherapy, based on 10 years of experience, as low dose‐rate (LDR) prostate brachytherapy is an accepted, effective and safe therapy for localized prostate cancer.

PATIENTS AND METHODS

Between April 1999 and December 2006, 734 consecutive patients were treated with clinically localized prostate cancer with a follow‐up of ≥30 months. No patients received external beam radiotherapy and 43% received hormonal therapy before brachytherapy; this therapy was given for 3–4 months. All patients had LDR prostate brachytherapy administered by one radiation oncologist. Biochemical failure was defined according to the ‘Phoenix consensus’.

RESULTS

The median follow‐up for the 734 patients was 55 months; 26 had a clinical relapse and 11 died from prostate cancer; 20 patients died from other illnesses. The 10‐year actuarial biochemical control was 92%, 84% and 65%, respectively (P < 0.001) for the low‐, intermediate‐ and high‐risk groups. Multivariate Cox regression analyses identified Gleason score and prostate‐specific antigen (PSA) level as independent prognostic factors for biochemical failure. The actuarial biochemical control with Gleason score was 88%, 76% and 67% for patients with a Gleason score of ≤6, 7 and >7, respectively (P < 0.001). The biochemical control was 90%, 80% and 42% for patients with a PSA level of ≤10, 10.1–20 and >20 ng/mL, respectively (P < 0.001). No patients reported incontinence after treatment. There was acute urinary retention in 22 (2.9%) patients. Logistic regression showed that the most significant factors correlating with the probability of catheterization were the pretreatment prostate volume and hormonal therapy.

CONCLUSIONS

The excellent long‐term results and low morbidity, and the many advantages of prostate brachytherapy over other treatments, show that brachytherapy is an effective treatment for clinically organ‐confined prostate cancer.     

Single application of high‐intensity focused ultrasound as a first‐line therapy for clinically localized prostate cancer: 5‐year outcomes

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? High‐intensity focused ultrasound (HIFU) therapy has been proposed for the treatment of localized prostate cancer (PCa) for all risk levels of tumour recurrence. The study adds data on the efficacy of a single HIFU application in the treatment of PCa with different risks of recurrence. Durable cancer control was achieved in 81.7% of patients with low‐risk disease, with rates of efficacy declining in intermediate‐ and high‐risk tumours. The data suggest that the principal domain for minimal invasive HIFU should be low‐risk disease.

OBJECTIVE

• ? To report cancer control results after a single application of high‐intensity focused ultrasonography (HIFU) in patients with localized prostate cancer (PCa), stratified by tumour recurrence risk according to D'Amico risk classification.

PATIENTS AND METHODS

• ? In a retrospective single‐centre study, we analysed the outcomes of patients with localized PCa who were treated with curative intent between December 2002 and October 2006 using an Ablatherm HIFU device (EDAP‐TMS, France).
• ? Transurethral resection of the prostate or adenomectomy were performed before HIFU to downsize large prostate glands.
• ? Oncological failure was determined by the occurrence of biochemical relapse, positive biopsy and/or metastasis. Biochemical relapse was defined as a PSA nadir +1.2 ng/mL (Stuttgart definition), or as a rise in PSA level to ≥0.5 ng/mL if PSA doubling time was ≤6 months. Kaplan–Meier analysis was performed for survival estimates.

RESULTS

• ? A total of 191 consecutive patients were included in the study. The median (range) patient age was 69.7 (51–82) years, and 38, 34 and 28% of these patients were in the low‐, intermediate‐ and high‐risk groups, respectively.
• ? The median (range) follow‐up was 52.8 (0.2–79.8) months.
• ? At 5 years, overall and cancer‐specific survival rates were 86.3% and 98.4%, respectively.
• ? Stratified by risk group, negative biopsy rates were 84.2%, 63.6%, and 67.5% (P = 0.032), 5‐year biochemical‐free survival rates were 84.8%, 64.9% and 54.9% (P < 0.01), and 5‐year disease‐free survival rates were 81.7%, 53.2% and 51.2% (P < 0.01), respectively.

CONCLUSION

• ? Single‐session HIFU is recommended as a curative approach in elderly patients with low‐risk PCa. Patients at higher risk of tumour progression should be counselled regarding the likely need for salvage therapy, including repeat HIFU.

     

The results of real-time brachytherapy for the management of low- and intermediate-risk prostate cancer in patients with prostate volumes up to 100 mL

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Historically, the majority of centres in the UK practise a pre‐plan brachytherapy technique which is limited to prostate volumes <50 ml. This study provides further evidence that it is technically possible to deliver a quality implant in a large prostate using real‐time brachytherapy and that the treatment is well tolerated. It has emphasized the value of functional parameters in selecting appropriate patients and concluded that prostate volumes up to 100 ml should not exclude patients from brachytherapy.

OBJECTIVES

• ? To report the results of real‐time brachytherapy in the management of low‐risk and intermediate‐risk prostate cancer in patients with prostate volumes up to 100 mL, over a 6‐year period.
• ? To prospectively determine whether prostate volume influences the ability to achieve a quality implant and therefore impact upon prostate‐specific antigen (PSA) relapse‐free survival, and urinary and rectal toxicity.

SUBJECTS AND METHODS

• ? In all, 216 men with localized prostate cancer were treated with real‐time prostate brachytherapy using ¹²⁵I implants between November 2003 and December 2009.
• ? Patient selection was based upon functional parameters; International Prostate Symptom Score (IPSS) and flowmetry.
• ? Patients had computed tomography imaging at 1 month to assess post‐implant dosimetry. PSA, IPSS and Radiation Therapy Oncology Group rectal toxicity scores were recorded prospectively over the follow‐up period.
• ? Patients with prostate volumes ≤50 mL and those with volumes >50 mL were compared.

RESULTS

• ? Overall PSA relapse‐free survival was 98.8%; 97.0% for intermediate‐risk patients and 100.0% for low‐risk patients. By volume, 98.5% of men with standard prostates were free from PSA relapse compared with 100.0% of men with large prostates.
• ? The mean post‐implant D90 was 177.0 Gy; 175.5 Gy in standard prostates and 183.5 Gy in large prostates.
• ? The overall acute urinary retention rate was 1.9%; 1.7% in standard prostates and 2.4% in large prostates. There were three urethral strictures, all in the standard prostate group. The mean IPSS increased to 11 and 14 at 3 months for the standard and large prostate groups, respectively, before settling to 2 above baseline for both groups at 12 months.
• ? There were no rectovesical fistulae. Persistent rectal bleeding was reported by one (0.5%) patient in the standard prostate group.

CONCLUSIONS

• ? Prostate brachytherapy is effective in the treatment of low‐risk and intermediate‐risk prostate cancer.
• ? It is technically possible to deliver a quality implant in a large prostate using real‐time brachytherapy.
• ? The treatment itself is well tolerated. Prostate volumes up to 100 mL should not exclude patients from brachytherapy providing either flow rate ≥14 mL/s or symptom score (IPSS) ≤ 10.

     

Oncological impact of neoadjuvant hormonal therapy on permanent iodine‐125 seed brachytherapy in patients with low‐ and intermediate‐risk prostate cancer

Objectives

To determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy.

Methods

Between January 2004 and November 2014, 564 patients underwent transperineal ultrasonography‐guided permanent iodine‐125 seed brachytherapy. We retrospectively analyzed low‐ or intermediate‐risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence‐free survival, progression‐free survival, cancer‐specific survival and overall survival.

Results

A total of 484 patients with low‐risk (259 patients) or intermediate‐risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5‐year actuarial biochemical recurrence‐free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence‐free survival outcomes in low‐ (P = 0.8949) or intermediate‐risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate‐specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence‐free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression‐free survival, cancer‐specific survival or overall survival.

Conclusions

In patients with low‐ or intermediate‐risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.     

Biochemical outcome after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal. The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.

OBJECTIVE

• ? To investigate the long‐term oncological outcome, during the PSA era, of patients with prostate cancer who were treated using high‐dose‐rate (HDR) brachy therapy (BT) combined with external beam radiation therapy (EBRT).

PATIENTS AND METHODS

• ? From June 1998 to April 2007, 313 patients with localized prostate cancer were treated with 46 Gy of EBRT to the pelvis with a HDR‐BT boost.
• ? The mean (median) follow‐up was 71 (68) months.
• ? Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, V.4.

RESULTS

• ? The 10‐year actuarial biochemical control was 100% for patients with no high‐risk criteria, 88% for patients with two intermediate‐risk criteria, 91% with one high‐risk criterion and 79% for patients with two to three high‐risk criteria (P= 0.004).
• ? The 10‐year cancer‐specific survival was 97% (standard deviation ±1%).
• ? The multivariate Cox regression analyses identified, Gleason score and T stage as independent prognostic factors for biochemical failure.
• ? Gleason score was the only factor to significantly affect distant metastases.
• ? Grade ≥3 late toxicity was not detected.

CONCLUSION

• ? The 10‐year results confirm the feasibility and effectiveness of EBRT with conformal HDR‐BT boost for patients with localised prostate cancer.

     

Evaluation of the Prostate Cancer Prevention Trial Risk calculator in a high‐risk screening population

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

OBJECTIVE

To evaluate the Prostate Cancer Prevention Trial (PCPT) risk calculator in a screening cohort of young, racially diverse, high‐risk men with a low baseline prostate‐specific antigen (PSA) level and enrolled in the Prostate Cancer Risk Assessment Program (PRAP). The PCPT calculator provides an assessment of prostate cancer risk based on age, PSA level, race, previous biopsy, and family history.

PATIENTS AND METHODS

Eligibility for PRAP includes men aged 35–69 years who are African‐American, have a family history of prostate cancer, or have a known BRCA1/2 mutation. PCPT risk scores were determined for PRAP participants, and were compared to observed prostate cancer rates.

RESULTS

In all, 624 participants were evaluated, including 382 (61.2%) African‐American men and 242 (38.7%) men with a family history of prostate cancer; the median (range) age was 49.0 (34.0–69.0) years and the median PSA level 0.9 (0.1–27.2) ng/mL. The PCPT risk score correlated with prostate cancer diagnosis, as the median baseline risk score in patients diagnosed with prostate cancer was 31.3%, vs 14.2% in patients not diagnosed with prostate cancer (P < 0.001). The PCPT calculator similarly stratified the risk of diagnosis of Gleason score ≥7 disease, as the median risk score was 36.2% in patients diagnosed with Gleason ≥7 prostate cancer vs 15.2% in all other participants (P < 0.001).

CONCLUSION

The PCPT risk calculator score was found to stratify prostate cancer risk in a cohort of young, primarily African‐American men with a low baseline PSA level. These results support further evaluation of this predictive tool for assessing the risk of prostate cancer in high‐risk men.     

Does laser ablation prostatectomy lead to oncological compromise?

OBJECTIVE

To assess the incidence and outcome of incidental prostate cancer detected at transurethral resection of the prostate (TURP), and to evaluate whether laser ablation prostatectomy would miss significant cancer by failing to provide tissue for histopathological analysis.

PATIENTS AND METHODS

Information on TURP‐detected prostate cancer was gathered from 1996 to 2006, from The South‐west Cancer Intelligence Service, hospital‐operating and coding records, histopathology databases and The British Association of Urological Surgeons Cancer Registry. We recorded the total number of prostate cancers diagnosed per year, number of TURPs performed, Gleason scores and patients outcomes.

RESULTS

TURP‐detected prostate cancer has declined since the relatively high rates (22%) recorded locally in 1996–97. Between 2001 and 2006, a mean (range) of 124 (111–135) prostate cancers were detected per year. Incidental cancers accounted for only 1.5–5.6% of all newly diagnosed prostate cancers per year. Incidental cancers had a mean (sem ) Gleason score of 5.7 (0.3) compared to 8.0 (0.3) in known cancers (P < 0.01) undergoing TURP. Of newly diagnosed patients, 82% were allocated to active surveillance, whilst 18% were started on hormone therapy, with no prostate cancer‐related deaths over a mean (sem , range) follow‐up of 49.7 (2.4, 11–81) months.

CONCLUSIONS

TURP mainly samples transitional‐zone tissue where tumours are relatively uncommon, and have a good prognosis. Our series of incidental TURP‐detected cancers showed an incidence in keeping with published data, and favourable histological and clinical outcomes. We suggest the lack of tissue should not discourage the use of laser prostatectomy surgery.     

Initial management of prostate cancer: first year experience with the Norwegian National Prostate Cancer Registry

Study Type – Therapy (individual cohort)
Level of Evidence 2b

OBJECTIVE

Improving a country’s management of cancer patients requires continuous evaluation, and requires the availability of population‐based prognostic and therapeutic variables. We aimed to document the national diagnostic and therapeutic tasks in Norwegian patients with prostate cancer diagnosed in 2004, with the 2003 European Association of Urology (EAU) guidelines representing the background.

PATIENTS AND METHODS

The Norwegian Prostate Cancer Registry (NoPCR) was established in 2004, and data collected during this first year were reviewed. The Tumour‐Node‐Metastasis group, prostate‐specific antigen (PSA) level and Gleason score were recorded as basic diagnostic variables, with the initial treatment. Patients with nonmetastatic T1‐T3 tumours were separated from those with advanced disease (T4 and/or N+ and/or M+). Patients with T1‐T3 tumours, aged ≤75 years, and in good health were candidates for curative local treatment (‘CurCands’) and were allocated to risk groups.

RESULTS

The compliance rate to the NoPCR was 96%; 2693 (72%) of 3744 eligible patients had T1‐T3 tumours and 833 (22%) had advanced disease (not classifiable in 218, 6%). Of 1650 CurCands (low‐risk 500; intermediate‐risk 453; high‐risk 697), 62% had radical prostatectomy or radiotherapy with or without hormone therapy, with the remaining 23% and 10% managed by, respectively, hormone therapy only or observation (other/unknown treatment, 6%).Only 64% of CurCands in the combined intermediate/high‐risk group had local treatment. In the low‐risk group local treatment was used in 57% of the patients, mainly in men with T2 tumours. In intermediate‐ and high‐risk CurCands, PSA was the strongest factor determining the performance of curative treatment. Adjuvant radiotherapy after radical prostatectomy was used in four of 142 patients with tumour‐involved margins.

CONCLUSION

In 2004 the initial management of prostate cancer in Norway was largely in accordance with the 2003 EAU guidelines, though there was some evidence of ‘over‐treatment’ of low‐risk patients and ‘under‐treatment’ of intermediate‐ and high‐risk patients. Some improvement of data collection by the NoPCR is warranted. National prostate cancer registries can contribute to improving the medical care of these patients.     

Associations of lower urinary tract symptoms with prostate-specific antigen levels, and screen-detected localized and advanced prostate cancer: a case-control study nested within the UK population-based ProtecT (Prostate testing for cancer and Treatment) study

OBJECTIVE

To determine associations of lower urinary tract symptoms (LUTS) with prostate‐specific antigen (PSA) levels and screen‐detected localized and advanced prostate cancer.

SUBJECTS AND METHODS

A case‐control study nested within the UK population‐based ProtecT (Prostate testing for cancer and Treatment) study. Men aged 50–69 years were invited for PSA testing and those with a PSA level of ≥3.0 ng/mL were invited for biopsy. We determined whether LUTS were associated with a PSA level of ≥3.0 ng/mL and prostate cancer using logistic regression models adjusted for age, family history of prostate cancer and PSA level as appropriate. Areas under receiver operating characteristic curves (AUC) were compared between models with and without symptoms.

RESULTS

In all, 65 871 men had a PSA test: 7251 had a PSA level of ≥3.0 ng/mL including 2467 subsequently diagnosed with prostate cancer (2119 localized, 348 advanced). LUTS were positively associated with a PSA level of ≥3.0 ng/mL: odds ratios (ORs) were 1.18 (95% confidence interval, CI 1.01–1.38), 1.69 (95% CI 1.32–2.16), and 1.60 (95% CI 1.33–1.93) for daytime urination frequency (hourly vs less frequent), urgency and hesitancy (most/all the time vs never), respectively. LUTS among men with a PSA level of ≥3 ng/mL were negatively associated with prostate cancer: ORs were 0.44 (95% CI 0.22–0.83), 0.74 (95% CI 0.63–0.87), and 0.83 (95% CI 0.73–0.94) for nocturia (4+ vs 0), leakage and hesitancy (occasionally/sometimes vs never), respectively. LUTS improved the prediction of a PSA level of ≥3.0 ng/mL (AUC 0.635 vs 0.606, P < 0.001) and prostate cancer (AUC 0.661 vs 0.638; P < 0.001).

CONCLUSIONS

A history of LUTS before PSA testing marginally improves the prediction of an individual’s risk for prostate cancer; men with a PSA level of ≥3 ng/mL and LUTS were more likely to be diagnosed with benign disease than prostate cancer.     

General application of the National Institute for Health and Clinical Excellence (NICE) guidance for active surveillance for men with prostate cancer is not appropriate in unscreened populations

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance (AS) is a well‐recognised management strategy to minimise the morbidity associated with radical treatment of prostate cancer. The National Institute for Health and Clinical Excellence guidelines initially suggested that all men with low‐risk prostate cancer should first be offered AS. The cohort of men with upstaging and upgrading of prostate cancer from diagnosis to final pathology has been described in North American and European populations. As the rate of PSA testing in Britain is lower than North America and parts of Europe, the risk of more advanced disease at diagnosis of prostate cancer is higher. The present study is one of the first to examine this cohort in a British population and found the rate of features of advanced disease (extracapsular extension, seminal vesicle involvement and Gleason 4 + 3, or 8–10) to be 37.2%.

OBJECTIVE

• ? To determine if the National Institute for Health and Clinical Excellence (NICE) guidelines for men with low‐risk prostate cancer were generally applicable in unscreened populations.

PATIENTS AND METHODS

• ? Retrospective analysis of prospectively collected case series from a single tertiary care centre in England.
• ? In all, 700 consecutive men treated for prostate cancer from 2005 by robot‐assisted laparoscopic prostatectomy (RALP) were included.
• ? Patients satisfying NICE criteria for low‐risk disease (PSA level < 10 ng/mL and Gleason score ≤ 6 and cT1–2a) had their pathological samples analysed for advanced disease, defined as extracapsular extension (ECE: pT3), seminal vesicle involvement (SVI), Gleason sum 7, or 8–10 or node‐positive disease.

RESULTS

• ? In all, 275 patients (39.2%) met the NICE low‐risk criteria, but pathologically advanced disease was found in 37.2% of this group.
• ? There was ECE in 71 patients (25.8%), 10 had SVI (3.6%), nine (3.3%) had Gleason score 7 (4 + 3), and 12 had Gleason sum 8–10 (4.4%).

CONCLUSIONS

• ? The NICE guidance was developed largely on data from North America where populations are highly screened using PSA testing. In the UK, many men with low‐risk disease features have high‐risk disease and the general applicability of the NICE guidance is questionable in unscreened populations.
• ? We recommend that radical therapy is discussed as an alternative option to active surveillance.

     

Urokinase‐plasminogen‐activator receptor expression in disseminated tumour cells in the bone marrow and peripheral blood of patients with clinically localized prostate cancer

OBJECTIVE

To evaluate the expression of urokinase‐plasminogen‐activator receptor (uPA‐R) in disseminated tumour cells (DTC) in bone marrow (BM) and peripheral blood (PB) of patients with clinically localized prostate cancer before radical prostatectomy (RP), and to assess the associations with pathological variables and prognosis.

PATIENTS AND METHODS

In all, 52 patients (47 with clinically localized cancer and five with benign prostatic hyperplasia, BPH, as controls) were prospectively enrolled. BM and PB samples were drawn before surgery. DTC were enriched using a commercial system, cytokeratin (CK) 8/18 was used to detect DTC, and uPA‐R expression was detected by dual‐immunostaining of the DTC. The final pathology of the RP specimen was compared with the results of immunostaining. Follow‐up was initiated to detect tumour relapse (defined as a prostate‐specific antigen (PSA) level of ≥0.2 ng/mL).

RESULTS

Overall, there was expression of ‘CK + uPA‐R’ in 60% of the BM and in 19% of the PB specimens. Expression of this marker in BM was most significantly increased in those with unfavourable Gleason scores (P = 0.004), followed by high‐risk cancer (P = 0.005). The relative risk for CK + uPA‐R expression in the BM was 3.1 times higher in high‐risk than in low‐risk prostate cancer. No relevant expression rates were detected for PB. In the control group, no patient showed CK or uPA‐R expression in BM or PB. The PSA‐recurrence free survival was significantly lower in patients with CK + uPA‐R‐positive BM cells (P = 0.01).

CONCLUSION

In this pilot study, the preoperative detection rate of CK + uPAR expression in BM of patients with prostate cancer increased with Gleason score and in those with high‐risk disease. All patients with a later PSA relapse had had uPA‐R expression in their DTC from the BM. DTC with uPA‐R expression was an adverse prognostic factor for prostate cancer.     

Primary full-gland prostate cryoablation in older men (> age of 75 years): results from 860 patients tracked with the COLD Registry

Study Type – Therapy (outcomes research) Level of Evidence 2c What's known on the subject? and What does the study add? Most elderly patient with prostate cancer undergo radiation therapy, but cryoablation has gained popularity. This study demonstrates the safety and efficiency of this new approach.

OBJECTIVE

• ? To report on the largest data set regarding outcomes for whole gland prostate cryoablation as a primary treatment of prostate cancer in older men, which we empirically defined as age >75 years.

MATERIALS AND METHODS

• ? The COLD (Cryo On‐Line Data) Registry consists of case report forms with pre‐ and post‐treatment information obtained from patients undergoing prostate cryoablation.
• ? A total of 860 patients were stratified into low‐, intermediate‐ and high‐risk groups (D'Amico 2003 risk definitions).
• ? Biochemical disease‐free survival (bDFS) was defined according to the traditional American Society for Therapeutic Radiology and Oncology definition (3 increases) and the newer (Phoenix) definition (nadir +2).
• ? Biopsy was performed at physician discretion but most commonly for cause if a patient had an increasing or suspicious prostate‐specific antigen level (PSA).

RESULTS

• ? The median age was 79 years (76–91) and the median follow‐up was 16 months (4–60).
• ? The 5‐year [95% confidence interval (CI)] bDFS for the entire population using ASTRO and Phoenix definitions was 79% (4%) and 62.6% (8.3%), respectively.
• ? Stratified by risk group, 5‐year bDFS (ASTRO) was 82.4% (7.9%), 78.3% (5.8%) and 77.6% (7.7%) for low, moderate and high risk, respectively.
• ? Using the Phoenix definition, 5‐year bDFS was 74.9%± 15.3%, 61.4%± 13.2% and 58.0%± 11.9% for low‐, moderate‐ and high‐risk groups, respectively.
• ? Incontinence was reported in eight patients (0.9%).

CONCLUSION

• ? Whole gland cryoablation in older men maintains oncological efficacy similar to that of younger men without increased morbidity.

     

The risk of prostate cancer amongst South Asian men in southern England: the PROCESS cohort study

OBJECTIVE

To reinvestigate whether South Asian men in the UK are at lower risk of being diagnosed with prostate cancer in a UK‐based retrospective cohort study and to examine possible reasons that may explain this.

PATIENTS AND METHODS

The catchment areas were predefined in four areas of southern England, and age‐ and race‐specific populations for those areas taken from census data. Cases were ascertained through review of multiple hospital sources, while race, other demographic factors, and medical history were determined using questionnaires sent to the men, hospital records review and death certificates. The South Asian group included men of Indian, Bangladeshi and Pakistani origin.

RESULTS

There was modest evidence of lower prostate cancer rates in South Asian men compared with their White neighbours (age‐adjusted rate ratio 0.81; 95% confidence interval 0.65–1.00). This difference did not reflect less use of prostate‐specific antigen (PSA) testing or differences in clinical features at presentation.

CONCLUSION

This study provides evidence of a lower incidence of prostate cancer amongst South Asian men living in England, in comparison with their White counterparts. If anything, South Asian men presented with clinical features of earlier disease suggesting that the reduced risk is unlikely to be an artefact of poorer access to health care.     

Predictive factors of biochemical recurrence after radical prostatectomy for high‐risk prostate cancer

Objective

To identify risk factors of biochemical recurrence after radical prostatectomy in high‐risk patients.

Methods

A total of 191 high‐risk prostate cancer patients according to the D'Amico classification treated with radical prostatectomy at a single institution between April 2000 and December 2013 were enrolled. The pathological evaluation including intraductal carcinoma of prostate was reassessed, and the clinical and pathological risk factors of biochemical recurrence were analyzed.

Results

The median follow up after radical prostatectomy was 49 months. The 5‐year biochemical recurrence‐free survival rate after radical prostatectomy in high‐risk prostate cancer patients was 41.6%. Initial prostate‐specific antigen, pathological Gleason score, seminal vesicle invasion, extraprostatic extension and intraductal carcinoma of the prostate were significantly associated with biochemical recurrence‐free survival. The 5‐year biochemical recurrence‐free survival rates in patients with zero, one, two and three of these risk factors were 92.9%, 70.7%, 38.3% and 28.8%, respectively. In patients with four or more factors, the biochemical recurrence‐free survival rate was 6.1% after 18 months.

Conclusions

In D'Amico high‐risk patients treated with radical prostatectomy, risk factors for biochemical recurrence can be identified. Patients with fewer risk factors have longer biochemical recurrence‐free survival, even among these high‐risk cases.     

The clinical phenotype of hereditary versus sporadic prostate cancer: HPC definition revisited

BACKGROUND

The definition of hereditary prostate cancer (HPC) is based on family history and age at onset. Intuitively, HPC is a serious subtype of prostate cancer but there are only limited data on the clinical phenotype of HPC. Here, we aimed to compare the prognosis of HPC to the sporadic form of prostate cancer (SPC).

METHODS

HPC patients were identified through a national registry of HPC families in the Netherlands, selecting patients diagnosed from the year 2000 onward (n = 324). SPC patients were identified from the Netherlands Cancer Registry (NCR) between 2003 and 2006 for a population‐based study into the genetic susceptibility of PC (n = 1,664). Detailed clinical data were collected by NCR‐registrars, using a standardized registration form. Follow‐up extended up to the end of 2013. Differences between the groups were evaluated by cross‐tabulations and tested for statistical significance while accounting for familial dependency of observations by GEE. Differences in progression‐free and overall survival were evaluated using χ² testing with GEE in a proportional‐hazards model.

RESULTS

HPC patients were on average 3 years younger at diagnosis, had lower PSA values, lower Gleason scores, and more often locally confined disease. Of the HPC patients, 35% had high‐risk disease (NICE‐criteria) versus 51% of the SPC patients. HPC patients were less often treated with active surveillance. Kaplan–Meier 5‐year progression‐free survival after radical prostatectomy was comparable for HPC (78%) and SPC (74%; P = 0.30). The 5‐year overall survival was 85% (95%CI 81–89%) for HPC versus 80% (95%CI 78–82%) for SPC (P = 0.03).

CONCLUSIONS

HPC has a favorable clinical phenotype but patients more often underwent radical treatment. The major limitation of HPC is the absence of a genetics‐based definition of HPC, which may lead to over‐diagnosis of PC in men with a family history of prostate cancer. The HPC definition should, therefore, be re‐evaluated, aiming at a reduction of over‐diagnosis and overtreatment among men with multiple relatives diagnosed with PC. Prostate 76:897–904, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.     

p53 immunochemistry is an independent prognostic marker for outcome in conservatively treated prostate cancer

OBJECTIVE

To determine whether p53 is an independent biomarker of prostate cancer outcome against currently used biomarkers in a cohort of conservatively treated prostate cancers with long‐term follow‐up available.

PATIENTS AND METHODS

We examined p53 expression by immunohistochemistry in a cohort of 705 patients with clinically localized prostate cancer, who were treated conservatively. Patients were selected through UK Cancer Registries. End‐points included prostate cancer death and overall death rates. Standard biological variables, including diagnostic serum PSA, contemporary Gleason scoring, clinical staging and cancer extent were available. p53 expression was measured semi‐quantitatively on microscopic examination and compared with current clinical biomarkers.

RESULTS

p53 over expression was a significant predictor of cause‐specific survival (hazard ratio [HR] 2.95, 95% CI 2.05–4.25, P < 0.001) and overall survival (HR 2.37, 95% CI 1.84–3.05, P < 0.001). In multivariate analysis including competing biological variables p53 expression was still significantly linked to prostate cancer survival (HR 1.51, 95% CI 1.04–2.19, P = 0.03) and overall survival (HR 1.57, 95% CI 1.21–2.05, P = 0.001).

CONCLUSIONS

We conclude that p53 may have a role in the future assessment of newly diagnosed prostate cancer, as it significantly adds to the current prognostic model.