Tag Archive for: active surveillance

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Article of the week: Free testosterone levels in PCa reclassification

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance

Ignacio F. San Francisco, Pablo A. Rojas, William C. DeWolf* and Abraham Morgentaler*

Departamento de Urología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile and *Division of Urological Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

OBJECTIVE

To determine whether total testosterone and free testosterone levels predict disease reclassification in a cohort of men with prostate cancer (PCa) on active surveillance (AS).

PATIENTS AND METHODS

Total testosterone and free testosterone concentrations were determined at the time the men began the AS protocol. Statistical analysis was performed using Student’s t-test and a chi-squared test to compare groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using univariate logistic regression. Receiver–operator characteristic curves were generated to determine the investigated testosterone thresholds. Kaplan–Meier curves were used to estimate time to disease reclassification. A Cox proportional hazard regression model was used for multivariate analysis. You can learn about testosterone here and so much more for your health.

RESULTS

A total of 154 men were included in the AS cohort, of whom 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone levels than those who were not reclassified (0.75 vs 1.02 ng/dL, P = 0.03). Men with free testosterone levels <0.45 ng/dL had a higher rate of disease reclassification than patients with free testosterone levels ≥0.45 (P = 0.032). Free testosterone levels <0.45 ng/dL were associated with a several-fold increase in the risk of disease reclassification (OR 4.3, 95% CI 1.25–14.73). Multivariate analysis showed that free testosterone and family history of PCa were independent predictors of disease reclassification.

CONCLUSIONS

Free testosterone levels were lower in men with PCa who had reclassification during AS. Men with moderately severe reductions in free testosterone level are at increased risk of disease reclassification.

Editorial: The importance of knowing testosterone levels in patients with prostate cancer

The paper by San Francisco et al. [1] in this issue of BJUI, reviews 154 patients with prostate cancer who were included in an active surveillance cohort. In all, 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone than those who were not reclassified. They concluded that on multivariate analysis, free testosterone and a family history of prostate cancer were independent predictors of disease reclassification. The authors acknowledge that this was a retrospective study of small size and the data was missing in some of the men, sex hormone-binding globulin (SHBG), luteinizing hormone and oestradiol were not measured. Nevertheless, this review adds to the increasing evidence that it is important to measure testosterone levels in men with prostate cancer.

Previous studies have indicated that a low testosterone level before treatment for prostate cancer is an independent predictor of a more aggressive high-grade cancer [2]. In addition to this, there appears to be an increased likelihood of extraprostatic disease at the time of diagnosis [3] and an unfavourable response to treatment [4].

Garcia-Cruz et al. [5] in 2012 reported that low testosterone bioavailability is related to a positive prostate cancer diagnosis in patients submitted for prostate biopsy. In a further study, he showed that low testosterone levels were related to poor prognosis factors in men with prostate cancer prior to treatment. Testosterone was inversely related to prostate cancer bilaterally and percentage of tumour in the biopsy. Higher testosterone levels were found in patients allocated to the low-risk progression group. In the multivariate analysis, older age and lower testosterone levels were related to a higher D’Amico risk of progression [5]. The researchers went on to show that higher SHBG and lower bioavailable testosterone are related to prostate cancer detection on biopsy. The study was a prospective analysis of 279 patients referred for prostate biopsy. Low bioavailable testosterone and high SHBG levels were related to a 4.9- and 3.2-fold increased risk of detection of prostate cancer on prostate biopsy taken due to an abnormal PSA result or an abnormal DRE [6].

Free testosterone accounts for about 1–2% of total testosterone and hence most circulating testosterone is bound to SHBG and as such, is inactive. Yamamoto et al. [7] had previously shown that men with a low free testosterone (<1.5 ng/dL) had an increased risk of a high Gleason score (>8) compared with men with higher free testosterone (8% vs 2%; P = 0.04). Additionally, a free testosterone level of <1.5 ng/dL was associated with increased risk of biochemical recurrence of tumour.

Morgentaler et al. [8] have been turning conventional wisdom upside down. They report on 13 symptomatic testosterone deficient men who also had untreated prostate cancer. The men received testosterone therapy while undergoing active surveillance for a median of 2.5 years. None of the men had aggressive or advanced prostate cancer and they were rigorously followed up. Despite effective treatment, neither the PSA level nor prostate volume showed any change. Follow-up biopsies were taken in all of the men at yearly intervals and none developed cancer progression.

It is intriguing to think that the decline in testosterone with age and comorbidities may contribute to tumorigenesis in the prostate. Clearly this study needs to be replicated with much larger numbers. But it seems reasonable to suggest that we ought to know about the hormonal environment existing in our patients with prostate cancer. This will of course, raise the even more controversial area of what to do about men with symptomatic hypogonadism with treated and untreated prostate cancer. There is limited data available on this issue.

Before considering testosterone therapy, the first step should be intensive lifestyle intervention; this is not only known to improve cancer survival, but raises total and free testosterone. Weight loss inhibits aromatase, and other complex cytokines, this reduces the suppression of the pituitary gonadal axis and conversion of testosterone to oestrogen, raising testosterone levels.

Read the full article

Michael Kirby*,†
*The Prostate Centre, London, and Institute of Diabetes for Older People (IDOP), Beds & Herts Postgraduate Medical School, Puckeridge Bury Campus, Luton, UK

References

  1. San Francisco I, Rojas P, Dewolf W, Morgentaler A. Low free testosterone predicts disease reclassification in men with prostate cancer undergoing active surveillance. BJU Int 2014; 114: 229–235
  2. Massengill JC, Sun L, Moul JW et al. Pretreatment total testosterone level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy. J Urol 2003; 169: 1670–1675
  3. Chen SS, Chen KK, Lin AT, Chang YH, Wu HH, Chang LS. The correlation between pretreatment serum hormone levels and treatment outcome for patients with prostatic cancer and bony metastasis. BJU Int 2002; 89: 710–713
  4. Ribeiro M, Ruff P, Falkson G. Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer. Am J Clin Oncol 1997; 20: 605–608
  5. Garcia-Cruz E, Piqueras M, Huguet J et al. Low testosterone levels are related to poor prognosis factors in men with prostate cancer prior to treatment. BJU Int 2012; 110: E541–546
  6. Garcia-Cruz E, Carrión Puig A, Garcia-Larrosa A et al. Higher sex hormone-binding globulin and lower bioavailable testosterone. Scand J Urol 2013; 47: 282–289
  7. Yamamoto S, Yonese J, Kawakame S et al. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol 2007; 52: 696–701
  8. Morgentaler A, Liphultz LI, Bennett R, Sweeney M, Avila D Jr, Khera M. Testosterone therapy in men with untreated prostate cancer. J Urol 2011; 185: 1256–1260
Read more articles of the week

Multiparametric MRI – Is the result convincing for AS patients?

Sir,

We read with interest the recent ‘Article of the Month’ by Park et al. in which they concluded that multi-parametric 3T-MRI can be used to predict adverse pathological features and to assess eligibility of patients for active surveillance (AS), in those initially meeting the PRIAS criteria [1]. Nevertheless, we would urge a degree of caution before widespread adoption of this strategy in patient selection for AS.

Firstly, it is accepted that there are false positives with multi-parametric MRI, with the addition of contrast only leading to a minor increase in accuracy, due to increased sensitivity being offset by reduced specificity [2]. Thus, it is imperative to at least make some effort to correlate tumour site on MRI with site on histopathology, which the authors acknowledge was not performed in their study.

Whilst realising that substantial technical difficulties arise in the correlation of imaging with radical prostatectomy specimens, we believe that, as a minimum, tumour side on MRI should be compared to tumour side on histopathology. This is relatively straightforward and could have been performed by Park et al., since 41% of the patients in the study were pathological stage T2a/b.

For example, an audit of 76 patients suitable for AS at our unit (Wirral University Teaching Hospital, UK), but electing for mapping transperineal template guided saturation biopsy, revealed that 53 patients had undergone MRI with diffusion weighted and 23 patients full multi-parametric dynamic contrast enhanced imaging, using a 1.5 T scanner. When analysed without correlation to tumour side the sensitivity was 83%, specificity was 68% and positive predictive value was 79%. However, when analysed with respect to tumour side on MRI with tumour side on histopathology the result becomes 73%, 61%, 79% respectively.

Park et al. concludes that MRI can be used to assess the eligibility of patients with PCa for AS, which is not backed up by their data. With only 11.7% exhibiting no tumour visible on imaging, the investigation will only exclude a relatively small proportion of patients from AS, whereas in the 88.3% with visible cancer on imaging, 50.2% did not have their cancer upgraded and 47.9% had favourable disease on final histology of the whole specimen. Thus, the authors have demonstrated a statistical significant correlation between identification of a lesion on MRI and the risks of upgrading and unfavourable disease, but not demonstrated that multi-parametric 3T MRI is a clinically useful investigation in this setting. In essence, introduction of MP-MRI would be likely to exclude more patients suitable for AS than those with adverse pathology. It seems more likely that it can only be built into a nomogram, rather than a stand-alone assessment tool.

Read the article

Debashis Sarkar*, Nijel J Parr**
*Research Fellow Urology, **Consultant Urologist, Wirral University Teaching Hospital, Upton, UK

Correspondence: Debashis Sarkar, Research Fellow Urology, Wirral University Teaching Hospital,
Upton, UK. e-mail: [email protected]

References

  1. Park BH, Jeon HG, Choo SH et al. Role of multiparametric 3.0-Tesla magnetic resonance imaging in patients with prostate cancer eligible for active surveillance. BJU Int 2014; 113: 864–870
  2. Tanimoto A, Nakashima J, Kohno H, Shinmoto H and Kuribayashi S. Prostate cancer screening: The clinical value of diffusion-weighted imaging and dynamic MR imaging in combination with T2-weighted imaging. J Magn Reson Imaging 2007; 25: 146–152

 

Article of the week: A protocol for transperineal sector biopsies of the prostate

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by prominent members of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Indications, results and safety profile of transperineal sector biopsies (TPSB) of the prostate: a single centre experience of 634 cases

Lona Vyas, Peter Acher, Janette Kinsella, Ben Challacombe, Richard T.M. Chang, Paul Sturch, Declan Cahill, Ashish Chandra and Richard Popert

The Urology Centre, Guy’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

Read the full article
OBJECTIVE

• To describe a protocol for transperineal sector biopsies (TPSB) of the prostate and present the clinical experience of this technique in a UK population.

PATIENTS AND METHODS

• A retrospective review of a single-centre experience of TPSB approach was undertaken that preferentially, but not exclusively, targeted the peripheral zone of the prostate with 24–38 cores using a ‘sector plan’. Procedures were carried out under general anaesthetic in most patients.

• Between January 2007 and August 2011, 634 consecutive patients underwent TPSB for the following indications: prior negative transrectal biopsy (TRB; 174 men); primary biopsy in men at risk of sepsis (153); further evaluation after low-risk disease diagnosed based on a 12-core TRB (307).

RESULTS

• Prostate cancer was found in 36% of men after a negative TRB; 17% of these had disease solely in anterior sectors.

• As a primary diagnostic strategy, prostate cancer was diagnosed in 54% of men (median PSA level was 7.4 ng/mL).

• Of men with Gleason 3+3 disease on TRB, 29% were upgraded and went on to have radical treatment.

• Postoperative urinary retention occurred in 11 (1.7%) men, two secondary to clots. Per-urethral bleeding requiring hospital stay occurred in two men. There were no cases of urosepsis.

CONCLUSIONS

• TPSB of the prostate has a role in defining disease previously missed or under-diagnosed by TRB. The procedure has low morbidity.

Read more articles of the week

 

Editorial: Is zero sepsis alone enough to justify transperineal prostate biopsy?

The landscape of infectious complications after TRUS-guided biopsy of the prostate has changed dramatically. While sepsis after TRUS-guided prostate biopsy has always been a concern for urologists performing this very common procedure, in the past couple of years a number of factors have added to these pre-existing concerns for urologists and patients alike.

First, key papers have reported the true incidence of sepsis and hospital re-admission after TRUS biopsy and have shown that these rates are increasing. Loeb et al. [1] reported that the 30-day re-admission rate in a Surveillance, Epidemiology and End Results (SEER)-Medicare population was 6.9% and that this rate is increasing. Nam et al. [2] similarly reported a 3.5-fold increase in hospital admissions after prostate biopsy in the previous 10 years, principally attributable to infection-related complications. These reports have been replicated around the world and there is consensus that this is a growing problem.

Second, there are increasing concerns about the emergence of resistant organisms, in particular, extended spectrum beta lactamase (ESBL), in regions where antibiotic use has contributed to the emergence of these strains [3]. Media attention has focused on this issue and has led to increased concerns among urologists and patients alike. It has also led to a requirement for extra precautions when assessing patients for prostate biopsy such that in some regions, rectal swabs are being taken to identify ESBL-carriers ahead of time. In a contemporary series, Taylor et al. [4] report that 19% of men undergoing transrectal prostate biopsy in Canada carry ciprofloxacin-resistant coliforms in rectal swabs. The thought of passing a needle through this flora into the prostate is somewhat disturbing; rectal swabs may become mandatory when offering a TRUS-guided biopsy to any patient and should absolutely be taken if planning a TRUS biopsy in someone who has travelled to South-East Asia in the preceding 6 months.

The Bloomberg News, in a well-researched report into antibiotic use in India and the emergence of resistant strains of Escherichia coli, reported some startling statistics about the overuse of antibiotics in that country, and described how the ‘perfect storm’ of antibiotic overuse, poverty and poor sanitation (half of the country’s 1.2 billion residents defaecate in the open), is contributing to the emergence of superbugs colonizing the gut of dwellers and visitors to India [5]. It is clear that even walking through a puddle in New Delhi puts a visitor at high risk of harbouring ESBL organisms in the rectum for many months after.

In this month’s BJUI, Vyas et al. [6] describe a consecutive series of 634 patients undergoing prostate biopsy at Guy’s Hospital in London using a transperineal template-guided approach, and report a sepsis rate of zero. They also report other notable factors including a 36% cancer detection rate in men who had previously undergone transrectal prostate biopsy with no evidence of malignancy and, in men on active surveillance for Gleason 6 prostate cancer, they observed upgrading to Gleason ≥7 cancer in 29% of cases after immediate re-staging biopsy using a transperineal approach. An even larger contemporary study from Pepe et al. [7] reports zero sepsis in a consecutive series of 3000 men undergoing transperineal prostate biopsy.

It is quite impossible to imagine such large series of prostate biopsies with no episodes of sepsis if performed using a transrectal approach. The documented increasing levels of ESBL and high levels of asymptomatic gut colonization, especially for those resident or travelling through South-East Asia, mean that adequate risk assessment and counselling of patients before TRUS biopsy is more important than ever before. A careful history regarding recent antibiotic use is also essential as previous recent use of quinolones is also a risk factor for infection after a transrectal biopsy [8].

While widespread adoption of a transperineal approach to prostate biopsy would have considerable resource and logistic issues, and inevitably would not be accepted by all urologists, the rising rate of infectious complications and of resistant organisms colonizing the rectum may mean that continuing with a transrectal approach becomes too risky and therefore unacceptable to patients and clinicians alike. While a transperineal approach also appears to add value in terms of more accurate staging and also facilitates the emerging interest in MRI fusion-guided biopsies and focal therapy, zero sepsis alone may be enough to convince many that a transrectal approach should no longer be preferred.

Read the full article

Declan G. Murphy*, Mahesha Weerakoon and Jeremy Grummet

*Division of Cancer Surgery, University of Melbourne, Peter MacCallum Cancer Centre, †Australian Prostate Cancer Research Centre, Epworth Richmond Hospital, and ‡Department of Urology, The Alfred Hospital, Melbourne, VIC, Australia

References

  1. Loeb S, Carter HB, Berndt SI, Ricker W, Schaeffer EM. Complications after prostate biopsy: data from SEER-Medicare. J Urol 2011; 186: 1830–1834
  2. Nam RK, Saskin R, Lee Y et al. Increasing hospital admission rates for urological complications after transrectal ultrasound guided prostate biopsy. J Urol 2010; 183: 963–968
  3. Williamson DA, Masters J, Freeman J, Roberts S. Travel-associated extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infection following transrectal ultrasound-guided prostate biopsy. BJU Int 2012; 109: E21–22
  4. Taylor S, Margolick J, Abughosh Z et al. Ciprofloxacin resistance in the faecal carriage of patients undergoing transrectal ultrasound guided prostate biopsy. BJU Int 2013; 111: 946–953
  5. Gale JN, Narayan A. Drug-defying germs from India speed post-antibiotic era. 2012; Available at: https://www.bloomberg.com/news/2012-05-07/drug-defying-germs-from-india-speed-post-antibiotic-era.html. Accessed June 2014
  6. Pepe PA, Aragona F. Morbidity after transperineal prostate biopsy in 3000 patients undergoing 12 vs 18 vs more than 24 needle cores. Urology 2013; 81: 1142–1146
  7. Patel U, Dasgupta P, Amoroso P, Challacombe B, Pilcher J, Kirby R. Infection after transrectal ultrasonography-guided prostate biopsy: increased relative risks after recent international travel or antibiotic use. BJU Int 2012; 109: 1781–1785

 

Read more articles of the week

A new take on GPS navigation? Summary of the June #urojc twitter debate.

The diagnosis and management of prostate cancer continues to rapidly evolve, with heavy debates at each stage of the evolution process. The key trade off between avoiding the over diagnosis and overtreatment of low risk indolent tumours, versus failing to diagnose and act on what may progress to aggressive disease, is an on going theme in the debate.

Research into various diagnostic tools to help both the patient and clinician stratify individual risk is on going, however the heavy consequence of undertreating perhaps leads more into active treatment than clinically necessary.

The June #urojc twitter debate focused on the new and hugely important paper by Klein E et al, to which we were given open access to courtesy of European Urology.  The authors of this US study focus on the potential underuse of Active Surveillance (AS), and propose a Genomic Prostate Score in order to help risk stratify patients considering both surveillance and active therapy. Based on three studies, a prostatectomy study, a biopsy study, and a validation study, a 17-gene assay was created which was shown to predict both high stage and high grade disease at diagnosis.

The debate kicked off with the suggestions from the hosts that at genomics may make their way into AS protocols

 

Which was rapidly agreed

However inevitably the issue of cost was raised

Parth Modi praised the study design and results, however raised a valid question

And the further issue of logistics of samples provided for genomic testing was debated

With the possibility of low disease volume in samples contributing

Which launched a debate as to whether for those with low volume disease, the discussion of opting for genomics was a discussion too far

Alternatives to genomics in predicting progressive disease were discussed. However again the cost of these tests were debated – although generally thought to be less expensive than genomic testing.

 

Followed by perhaps an early contender for best tweet…

 

The host again posed an on point question

With responses suggesting there remains room for further work until genomics plays a role in day-to-day treatment plans

David Canes helped to put the debate into real terms by using an example case for discussion, which raised the point of interpretation of results being dependent on likely treatment decision, not necessarily treatment decision based fully on results

Which raised some slightly more pragmatic suggestions

GPS results however are not necessarily clear-cut. Like all prognostic indicators, they can be interpreted in variable ways. Is there a possibility that they could add to the quagmire in the decision making process for patients?

Ultimately the theme of the debate was summed up excellently by Matt Cooperberg. GPS is not offering a definitive strategy to decide who will and will not progress, or who should decide on active treatment. It does however mark a movement into individualised care, which may well be the future for prostate cancer treatment

Congratulations to David Canes for winning the Best Tweet prize which is a complimentary manuscript to Research Reports in Urology published by @DovePress.

Many thanks to all of those who participated in the debate. We look forward to next month’s #urojc discussion!

Sophia Cashman is a first year urology trainee working in the East of England region, UK. Her main areas of interest are female and functional urology. @soph_cash

 

Article of the week: PCa-specific mortality increased in older men with low-risk disease

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by prominent members of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Aizer discussing his paper.

If you only have time to read one article this week, it should be this one

Initial management of prostate-specific antigen-detected, low-risk prostate cancer and the risk of death from prostate cancer

Ayal A. Aizer*, Ming-Hui Chen, Jona Hattangadi* and Anthony V. D’Amico

*Harvard Radiation Oncology Program, Boston, MA, Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, and, Department of Statistics, University of Connecticut, Storrs, CT, USA

Read the full article
OBJECTIVE

• To evaluate whether older age in men with low-risk prostate cancer increases the risk of prostate cancer-specific mortality (PCSM) when non-curative approaches are selected as initial management.

PATIENTS AND METHODS

• The study cohort consisted of 27 969 men, with a median age of 67 years, with prostate-specific antigen (PSA)-detected, low-risk prostate cancer (clinical category T1c, Gleason score ≤6, and PSA ≤10) identified by the Surveillance, Epidemiology and End Results programme between 2004 and 2007.

• Fine and Gray’s competing risk regression analysis was used to evaluate whether management with non-curative vs curative therapy was associated with an increased risk of PCSM after adjusting for PSA level, age at diagnosis and year of diagnosis.

RESULTS

• After a median follow-up of 2.75 years, 1121 men died, 60 (5.4%) from prostate cancer.

• Both older age (adjusted hazard ratio [AHR] 1.05; 95% confidence interval (CI) 1.02–1.08; P < 0.001) and non-curative treatment (AHR 3.34; 95% CI 1.97–5.67; P < 0.001) were significantly associated with an increased risk of PCSM.

• Men > the median age experienced increased estimates of PCSM when treated with non-curative as opposed to curative intent (P< 0.001); this finding was not seen in men ≤ the median age (P = 0.17).

CONCLUSION

• Pending prospective validation, our study suggests that non-curative approaches for older men with ‘low-risk’ prostate cancer result in an increased risk of PCSM, suggesting the need for alternative approaches to exclude occult, high grade prostate cancer in these men.

 

Read Previous Articles of the Week

 

Editorial: The age old question: who benefits from prostate cancer treatment?

Widespread PSA-based screening has dramatically altered the profile of newly diagnosed prostate cancer in many countries. Although screening effectively decreases the rates of metastatic disease and prostate cancer death [1], the increasing proportion of low-risk disease necessitates a critical assessment of the need for aggressive therapy.

Active surveillance and watchful waiting are potential alternatives to delay or avoid the need for treatment in carefully selected patients. The key issue is determining which patients are appropriate for conservative management. Although these approaches are often targeted toward elderly men, such men are more likely to be diagnosed with high-risk disease. A recent study by Scosyrev et al. [2] raised concern about excess prostate cancer mortality attributable to under-treatment in the elderly.

Overall, there is very little Level 1 evidence to guide prostate cancer treatment selection. One such trial, the Swedish Prostate Cancer Group 4 (SPCG-4), showed that radical prostatectomy significantly improved survival compared with watchful waiting [3]; however, that study examined a primarily clinically detected population from the 1990s. Subsequently, the Prostate Cancer Intervention versus Observation Trial (PIVOT) randomized US male veterans diagnosed with prostate cancer from 1994 to 2002 to radical prostatectomy vs observation [4]. At 10 years, they reported no significant difference in overall survival between the two arms in the intent-to-treat analysis (hazard ratio 0.88; 95% CI 0.71–1.08, P = 0.22). However, that study was smaller than anticipated owing to difficulty with recruitment and there was a high rate of crossovers between the intervention and observation arms. Per-protocol analysis was not reported for PIVOT and the prostate cancer landscape has continued to change in the past decade, raising unanswered questions over what the results would be if we compared contemporary men who were actually treated to those who were not.

This is the knowledge gap addressed by Aizer et al. [5] who used Surveillance, Epidemiology and End Results (SEER) data for 27 969 US men diagnosed with low-risk prostate cancer from 2004 to 2007. Overall, 67.1% of these men received radical prostatectomy or radiation therapy, while >30% underwent active surveillance or watchful waiting. Using competing risks regression, they showed that both age and non-curative treatment were associated with a significantly higher short-term prostate cancer-specific mortality. These results should be interpreted with caution, however, since they comprise observational data with great potential for confounding. Interestingly, at a short median follow-up of only 2.75 years, 5.4% of these men with presumed low-risk disease died from prostate cancer. Recently, there has been debate over whether Gleason 6 disease should really be considered a cancer [6], but these data highlight the limitations of current clinical staging, such that even presumed low-risk disease may be understaged. The authors suggest that use of a more extended biopsy scheme before active surveillance might reduce the risk of early progression due to undersampling. MRI represents another potential non-invasive treatment method to improve clinical staging and patient selection for active surveillance in the future [7].

Stacy Loeb
Department of Urology, New York University, New York, NY, USA

Read the full article

References

  1. Schroder FH, Hugosson J, Roobol MJ et al. Prostate-cancer mortality at 11 years of follow-upN Engl J Med 2012; 366: 981–990
  2. Scosyrev E, Messing EM, Mohile S et al. Prostate cancer in the elderly: frequency of advanced disease at presentation and disease-specific mortalityCancer 2012; 118: 3062–3070
  3. Bill-Axelson A, Holmberg L, Ruutu M et al. Radical prostatectomy versus watchful waiting in early prostate cancerN Engl J Med 2011; 364: 1708–1717
  4. Wilt TJ, Brawer MK, Jones KM et al. Radical prostatectomy versus observation for localized prostate cancerN Engl J Med 2012;367: 203–212
  5. Aizer AA, Chen MH, Hattangadi J, D’Amico AV. Initial management of prostate-specific-antigen-detected, low-risk prostate cancer and the risk of death from prostate cancerBJU Int 2014; 113: 43–50
  6. Carter HB, Partin AW, Walsh PC et al. Gleason score 6 adenocarcinoma: should it be labeled as cancer? J Clin Oncol 2012; 30:4294–4296
  7. Vargas HA, Akin O, Afaq A et al. Magnetic Resonance Imaging for Predicting Prostate Biopsy Findings in Patients Considered for Active Surveillance of Clinically Low Risk Prostate CancerJ Urol 2012; 188: 1732–1738

 

Video: PCa in older men, is it really low-grade disease?

 

Initial management of prostate-specific antigen-detected, low-risk prostate cancer and the risk of death from prostate cancer

Ayal A. Aizer*, Ming-Hui Chen, Jona Hattangadi* and Anthony V. D’Amico

*Harvard Radiation Oncology Program, Boston, MA, Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, and, Department of Statistics, University of Connecticut, Storrs, CT, USA

Read the full article
OBJECTIVE

• To evaluate whether older age in men with low-risk prostate cancer increases the risk of prostate cancer-specific mortality (PCSM) when non-curative approaches are selected as initial management.

PATIENTS AND METHODS

• The study cohort consisted of 27 969 men, with a median age of 67 years, with prostate-specific antigen (PSA)-detected, low-risk prostate cancer (clinical category T1c, Gleason score ≤6, and PSA ≤10) identified by the Surveillance, Epidemiology and End Results programme between 2004 and 2007.

• Fine and Gray’s competing risk regression analysis was used to evaluate whether management with non-curative vs curative therapy was associated with an increased risk of PCSM after adjusting for PSA level, age at diagnosis and year of diagnosis.

RESULTS

• After a median follow-up of 2.75 years, 1121 men died, 60 (5.4%) from prostate cancer.

• Both older age (adjusted hazard ratio [AHR] 1.05; 95% confidence interval (CI) 1.02–1.08; P < 0.001) and non-curative treatment (AHR 3.34; 95% CI 1.97–5.67; P < 0.001) were significantly associated with an increased risk of PCSM.

• Men > the median age experienced increased estimates of PCSM when treated with non-curative as opposed to curative intent (P< 0.001); this finding was not seen in men ≤ the median age (P = 0.17).

CONCLUSION

• Pending prospective validation, our study suggests that non-curative approaches for older men with ‘low-risk’ prostate cancer result in an increased risk of PCSM, suggesting the need for alternative approaches to exclude occult, high grade prostate cancer in these men.

 

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