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Article of the week: The ProtecT trial: analysis of the patient cohort, baseline risk stratification and disease progression

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Every week, the Editor-in-Chief selects an 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 this post, there is an editorial written by a prominent member of the urological community and a podcast produced by on of our resident podcasters. Please use the comment buttons below to join the conversation.

If you only have time to read one article this week, we recommend this one. 

The ProtecT trial: analysis of the patient cohort, baseline risk stratification and disease progression

Richard J. Bryant*, Jon Oxley†, Grace J. Young‡§, Janet A. Lane‡§, Chris Metcalfe‡§, Michael Davis‡, Emma L. Turner‡, Richard M. Martin‡, John R. Goepel, Murali Varma**, David F. Griffiths**, Ken Grigor††, Nick Mayer‡‡, Anne Y. Warren§§, Selina Bhattarai¶¶, John Dormer‡‡, Malcolm Mason***, John Staffurth†††, EleanorWalsh‡, Derek J. Rosario‡‡‡, James W.F. Catto‡‡‡, David E. Neal*§§§, Jenny L.Donovan‡¶¶¶, Freddie C. Hamdy* and for the ProtecT Study Group1

*Nuffield Department of Surgical Sciences, University of Oxford, Oxford, †Department of Cellular Pathology, North Bristol NHS Trust, ‡Bristol Medical School, §The Bristol Randomised Trials Collaboration, University of Bristol, Bristol, Department of Pathology, Royal Hallamshire Hospital, Sheffield, **Department of Pathology, University Hospital of Wales, Cardiff, ††Department of Pathology, Western General Hospital, Edinburgh, ‡‡Department of Pathology, University of Leicester, Leicester, §§Department of Pathology, University of Cambridge, Cambridge, ¶¶Department of Pathology, Leeds Teaching Hospitals NHS Trust, Leeds, ***School of Medicine, Cardiff University, Cardiff, †††Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, ‡‡‡Academic Urology Unit, University of Sheffield, Sheffield, §§§Academic Urology Group, University of Cambridge, Cambridge, and ¶¶¶National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West, University Hospitals Bristol NHS Foundation Trust, Bristol, UK

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Abstract

Objective

To test the hypothesis that the baseline clinico‐pathological features of the men with localized prostate cancer (PCa) included in the ProtecT (Prostate Testing for Cancer and Treatment) trial who progressed (n = 198) at a 10‐year median follow‐up were different from those of men with stable disease (n = 1409).

Patients and Methods

We stratified the study participants at baseline according to risk of progression using clinical disease stage, pathological grade and PSA level, using Cox proportional hazard models.

Fig.1. Cumulative incidence of disease progression by International Society of Urological Pathology Grade Group (GG) and clinical stage, based on intention to treat groups. AM, active monitoring.

Results

The findings showed that 34% of participants (n = 505) had intermediate‐ or high‐risk PCa, and 66% (n = 973) had low‐risk PCa. Of 198 participants who progressed, 101 (51%) had baseline International Society of Urological Pathology Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5%, respectively, for 1409 participants without progression (P < 0.001). In participants with progression, 38% and 62% had baseline low‐ and intermediate‐/high‐risk disease, compared with 69% and 31% of participants with stable disease (P < 0.001). Treatment received, age (65–69 vs 50–64 years), PSA level, Grade Group, clinical stage, risk group, number of positive cores, tumour length and perineural invasion were associated with time to progression (P ≤ 0.005). Men progressing after surgery (n = 19) were more likely to have a higher Grade Group and pathological stage at surgery, larger tumours, lymph node involvement and positive margins.

Conclusions

We demonstrate that one‐third of the ProtecT cohort consists of people with intermediate‐/high‐risk disease, and the outcomes data at an average of 10 years’ follow‐up are generalizable beyond men with low‐risk PCa.

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Editorial: Estimating the threat posed by prostate cancer

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What is the threat posed by your disease? This is how I begin all my conversations with men who have newly diagnosed prostate cancer. For men with obvious metastatic disease, the conversation is relatively simple. They have a systemic disease that requires systemic therapy with anti‐androgen medications. However, for men with localised prostate cancer the conversation is more difficult, as it is unclear when the disease will become clinically apparent. The report by Bryant et al. [1,2] in this issue of the BJUI summarising the Prostate Testing for Cancer and Treatment (ProtecT) trial findings has provided us with critical data concerning the natural history of screen‐detected prostate cancer and the relative impact of treatment.

The ProtecT trial data are unique, in that the study is embedded within a screening trial [2]. The patients recruited to the study reflect outcomes of men with cancer identified by PSA testing. The study population differs from men enrolled in the Scandinavian Prostate Cancer Group Study number 4 (SPCG‐4), who were primarily diagnosed clinically and therefore do not have the lead time associated with screening [3]. The study cohort also differs from the men enrolled in the Prostate Intervention Versus Observation Trial (PIVOT), who were generally older and therefore more often succumbed to competing medical problems during follow‐up [4]. The former group is likely to have a higher incidence of clinically significant disease; the latter group is likely to have a lower disease‐specific mortality.

While the ProtecT trial data offer a reasonable approximation of clinical practice, the ProtecT patient cohort differs from contemporary North American patients who likely have had several PSA tests prior to the one that prompted a prostate biopsy, and from contemporary UK patients who now undergo biopsy as a result of a lesion seen on MRI. The former group is likely to have a higher incidence of low‐grade disease; the latter group is more likely to have a higher incidence of high‐grade disease. Fortunately, these selection biases do not detract significantly from the fundamental messages of the ProtecT trial.

So how have Bryant et al. [1] helped us? A review of Table 1 in the paper, confirms that the Gleason Grade Group is the most powerful predictor of disease progression and long‐term survival for men with screen‐detected disease. PSA testing preferentially identifies men with low‐grade disease, primarily because low‐grade disease is much more common than high‐grade disease. Only 6% of the ProtecT cohort had Gleason Grade Group ≥3 disease, but these men accounted for 37% of the men who progressed. In comparison, 92% of the cohort had Gleason Grade Group 1 disease and only 8% of these men showed signs of progression. Among those men who underwent a radical prostatectomy, five of the seven men who developed metastases or died from their disease had Gleason Grade Group ≥3. Clinicians can now confidently counsel men considering active surveillance regarding the 10‐year estimates of disease progression based upon the biopsy Gleason Grade Group alone.

But Bryant’s team provided additional important information. They have shown that clinical stage and preoperative PSA levels also contribute important prognostic information and when men are classified by Risk Group, men with intermediate‐risk disease have over four‐times the probability of progressing within 10 years of diagnosis when compared to men in the low‐risk group. This is very relevant to men in their 50s and 60s contemplating active surveillance and should inject a note of caution for men in their 70s.

Bryant et al. [1] also showed us that other factors were less valuable in predicting long‐term outcomes. Patient age, the number of cores positive, the presence of perineural invasion, provided some evidence of increased risk, but were much less persuasive in helping men decide upon an appropriate treatment pathway.

The authors close their manuscript with the statement that baseline clinical and pathological features associated with men with newly diagnosed prostate cancer are not strong enough to reliably predict individual progression. While this may be true, I do not think they give sufficient credit to their accomplishments. Their data are the most relevant outcomes data for men with screen‐detected prostate cancer, providing them with accurate estimates of the probability of disease progression, or lack thereof, over a 10‐year horizon. The infrequent disease progression among men with Gleason Grade Group 1 was a surprise finding from the ProtecT study. Since then, our protocols and tools for conducting active surveillance have improved significantly. The 15‐year data are likely to be available in another 2–3 years; hopefully, they will remain as encouraging.

For now, we highly recommend men to learn about the symptoms of prostate cancer so that they can detect any problems from an early stage. This is very important mainly because the symptoms for BPH and prostate cancer can be very similar and it is crucial for men to know when they’ll need a bph treatment or a PHI test. 

by Peter Albertsen

References

  1. Bryant R, Oxley J, Young G et al. The ProtecT trial: analysis of the patient cohort, baseline risk stratification and disease progression. BJU Int 2020; 125: 505– 14
  2. Hamdy FC, Donovan JL, Lane JA et al. 10‐year outcomes after monitoring, surgery or radiotherapy for localized prostate cancer. N Eng J Med 2016; 375: 1415– 24
  3. Bill‐Axelson A, Holmberg L, Garmo H et al. Radical prostatectomy or watchful waiting in prostate cancer – 29 year follow up. N Eng J Med 2018; 379: 2319– 29
  4. Wilt TJ, Brawer MK, Jones KM et al. Radical prostatectomy versus observation for localized prostate cancer. N Eng J Med 2012; 367: 203– 13

Article of the Week: Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000–2012

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Every Week the Editor-in-Chief selects an 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.

Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000–2012

Daniela Danneman*, Linda Drevin†, Brett Delahunt‡, Hemamali Samaratunga§¶, David Robinson**, Ola Bratt††‡‡, Stacy Loeb§§ Par Stattin¶¶*** and Lars Egevad*†††

 

*Department of Oncology-Pathology, Karolinska Institute, Stockholm, † Regional Cancer Centre, Uppsala University Hospital, Uppsala, Sweden, ‡Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand, §Aquesta Pathology, The University of Queensland School of Medicine, Brisbane, Qld, Australia, **Department of Urology, Ryhov County Hospital, Jonkoping, Sweden, ††Department of Urology, Cambridge University Hospitals, Cambridge, UK, ‡‡Department of Translational Medicine, Lund University, Lund, Sweden, §§Department of Urology and Population Health, New York University and Manhattan Veterans Affairs Medical Centre, New York, NY, USA, ¶¶Department of Surgical and Perioperative Sciences, Urology and Andrology, Umea University, Umea, ***Department of Surgical Sciences, Uppsala University, Uppsala, Umea, and †††Department of Pathology, Karolinska University Hospital, Stockholm, Sweden

 

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Abstract

Objectives

To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1–5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9–10) better predict the RP grade.

Patients and Methods

All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1–2 M0/X prostate cancer on needle biopsy; were aged ≤70 years; had serum PSA concentration of <20 ng/mL; and underwent a RP <6 months after diagnosis as their primary treatment.

aotw-jan-4-2017-results

Results

Prediction of RP Gleason score increased from 55 to 68% between 2000 and 2012. Most of the increase occurred before 2005 (nine percentage points; P < 0.001); however, when adjusting for Gleason score and year of diagnosis in a multivariable analysis, the prediction of RP Gleason score decreased over time (odds ratio [OR] 0.98; P < 0.002). A change in the ISUP grades would have led to a decreasing agreement between biopsy and RP grades over time, from 68% in 2000 to 57% in 2012, with an OR of 0.95 in multivariable analysis (P < 0.001).

Conclusion

Agreement between biopsy and RP Gleason score improved from 2000 to 2012, with most of the improvement occurring before the 2005 ISUP grading revision. Had ISUP grades been used instead of Gleason score, the agreement between biopsy and RP grade would have decreased, probably because of its separation of Gleason score 7 into ISUP grades 2 and 3 (Gleason score 3 + 4 vs 4 + 3).

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Editorial: The prognostic value of prostate biopsy grade – Forever a product of sampling

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The ability to project clinical outcomes based on limited data is crucial to the practice of medicine. This principle is particularly germane to the management of prostate cancer, where clinical outcomes vary widely. In the current issue of BJUI, Danneman et al. [1] assess pathological grade concordance between diagnostic needle biopsy and subsequent radical prostatectomy specimens from 2000 to 2012. The authors observed increased concordance of biopsy and prostatectomy Gleason scores over the time period (from 55% in 2000 to 68% in 2012) with the majority of improvement occurring before 2005. Interestingly, concordance decreased over time (from 68 to 57%) with use of the newly revised grading system. These and other findings led to the proposal that increased concordance was attributable more to the elimination of Gleason scores 2–5 than the systematic change in grading itself.

We commend the authors for exploring this important topic. Our ability to derive meaningful information on disease biology and behaviour from biopsy specimens is essential to counselling patients on the many available management options. At the same time, biopsy grading is inherently limited in its ability to predict overall prostate pathology because it is not only dependent on architecture and morphology, but also on the, admittedly minimal, sample of tissue obtained. As such, we should be cautious in using terms such as ‘undergrading’ in describing biopsy specimens, which may have been properly graded, but simply lacked the higher grade tumour observed at prostatectomy. In reality, such a phenomenon represents undersampling rather than undergrading, and there is hope that such undersampling will decrease with improved methods of detection, such as multiparametric MRI/TRUS fusion-guided biopsy.

Notably, the authors refer to the updated grading system, which was first described by Dr Epstein and validated in a multi-institutional study [2] before the 2014 International Society of Urological Pathology (ISUP) consensus conference, as ISUP grades 1–5. For clarity, it should be noted that the initial report and validation of the new system [2], the 2014 ISUP consensus conference proceedings [3] and the WHO 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs [4], have all described the new system based on grade groups 1–5. Consistent use of the adopted terminology will be helpful moving forward.

Nonetheless, there are several potential explanations for the patterns observed in the present study. As the authors note, lower concordance based on the grade group system can be largely explained by the more precise classification of Gleason score 7 cancers. Based on evidence of disparate outcomes in Gleason score 3+4 = 7 and 4+3 = 7 disease [5], the ISUP system distinctly classifies these cancers as prognostic grades 2 and 3, respectively. Certainly, when compared with a system in which Gleason score 7 represents a single classification, one would expect poorer concordance in the more widely distributed group. We believe the clinical utility of separating these classifications far outweighs a modest decrease in concordance, which may be explained by other factors in any case. Previous studies have shown the importance of subdividing the Gleason score 7 population when comparing grading systems [6]. Furthermore, details are not provided as to whether a global grade was assigned to biopsy, a common practice in Sweden, which is not the currently recommended practice. That 5–7% of specimens received a Gleason score < 6 calls into question whether contemporary recommendations were fully adopted during the study period.

Regardless, Danneman et al. elegantly highlight the frequency with which biopsy and prostatectomy grades are discordant, and the fact that, to date, pathological grading remains a subjective practice. As noted, there are widespread efforts to address both of these issues, including the use of targeted biopsies and tissue-based genomic markers. Until these practices are well-validated and widely implemented, there are several reasons to believe the most recent grade group system will improve contemporary practice, despite limited concordance. For one, use of a more intuitive scale ranging from 1 to 5 should prove easier for patients to understand, a significant consideration in light of the information overload patients absorb with a new diagnosis of cancer. Furthermore, available data to this point demonstrate excellent prognostic value. In one study from Johns Hopkins, the revised Grade Group system showed improved accuracy for predicting 5-year metastasis (C-index 0.80 vs 0.70) and 10-year prostate cancer-specific mortality (C-index 0.77 vs 0.64) as compared with the original Gleason score [7].

Until truly objective methods of pathological assessment emerge, additional validation of the new grade group system is likely to further support its use moving forward. As Danneman et al. point out, however, we must keep in mind that biopsy, although perhaps our most useful tool, captures only a small fraction of the overall picture.

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Jeffrey J. Tosoian* and Jonathan I. Epstein*,†,‡ *James Buchanan

 

Brady Urological Institute and Department of Urology, †Department of Pathology, Johns Hopkins University School of Medicine, and ‡Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

 

References

 

1 Danneman D, Drevin L, Delahunt B et al. Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000–2012. BJU Int 2017; 119: 50–6

 

2 Pierorazio PM, Walsh PC, Partin AW, Epstein JI. Prognostic gleason grade grouping: data based on the modified gleason scoring system. BJU Int 2013; 111: 753–60

 

3 Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA. The 2014 international society of urological pathology (isup) consensus conference on gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol 2016; 40:244–52

 

4 Moch H, Humphrey P, Ulbright T, Reuter V. WHO classification of tumours: pathology and genetics.Tumours of the Urinary and Male Reproductive System. Lyon, France:IARC Press; 2016.

 

5 Eggener SE, Scardino PT, Walsh PC et al. Predicting 15-year prostate cancer specific mortality after radical prostatectomy. J Urol 2011; 185: 869–75

 

6 Lee MC, Dong F, Stephenson AJ, Jones JS, Magi-Galluzzi C, Klein EA. The Epstein criteria predict for organ-confined but not insignificant disease and a high likelihood of cure at radical prostatectomy. Eur. Urol 2010; 58: 90–5

 

7 Faraj SF, Bezerra SM, Yousefi K et al. Clinical validation of the 2005 ISUP gleason grading system in a cohort of intermediate and high risk men undergoing radical prostatectomy. PLoS One 2016; 11: e0146189

 

Is Gleason 6 really cancer?

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The recently published Viewpoint of the National Cancer Institute working group on “Overdiagnosis and Overtreatment in Cancer” by Esserman and colleagues [1] raises continued discussion as to whether some lesions currently classified as carcinomas should have the designation of “cancer” removed, based on low rates of progression, death, and other adverse outcomes. Pertinent to those interested in urology, a central example in the article is prostatic adenocarcinoma.

One simple answer to this question is that to a small extent, a subgroup of prostatic lesions has already been reclassified as not cancer: In current practice, needle biopsy or radical prostatectomy specimens with an overall Gleason score (GS) of 5 or less are now quite rare in current practice. This shift is due in part to modern updates to the Gleason grading system [2], under which many tumors now reach thresholds for GS6 or above. However, at least some lesions previously considered adenocarcinoma with a low overall GS would now be categorized as atypical adenomatous hyperplasia or adenosis in the era of immunohistochemistry for markers of prostatic basal cells. Nonetheless, the current and more controversial debate surrounds whether some (or all?) tumors currently classified as GS6 could be recategorized as not “cancer”.

Arguments against removing the cancer designation from some prostatic adenocarcinomas:

A major difficulty from the pathologic standpoint in adopting a non-cancer nomenclature for some tumors (such as GS6 adenocarcinomas) is that the Gleason pattern 3 component of a GS 3+3=6 tumor (small, round prostatic glands that lack a basal cell layer and infiltrate between benign glands) is for all intents and purposes identical to the Gleason pattern 3 component of a GS 3+4=7 or higher prostate cancer. These similarities are not limited exclusively to the microscopic appearance but also include a number of immunohistochemical and molecular features, as summarized in a recent article addressing this question [3]. Therefore, no pathologic features are as yet defined that ideally predict whether Gleason pattern 3 glands in a biopsy specimen represent a pure GS6 tumor or a component of higher-grade tumor in which the high-grade component is not represented. Not surprisingly, it is not unusual for tumors with GS6 on needle biopsy to be upgraded to GS7 at radical prostatectomy [3], particularly when a high tumor volume is present in the needle biopsy.

Gleason pattern 3 glands from a GS7 tumor, identical to those of a GS6 tumor.

To compare to other cancers with low risk of aggressive behavior, basal cell carcinoma and squamous cell carcinoma of the skin similarly show locally infiltrative properties, supporting their classification as carcinomas by a classical pathologic definition. Despite that the word “carcinoma” continues to be used for these tumors, most patients are not concerned that they have a life-threatening disease and these lesions are even excluded from the American Cancer Society statistics regarding cancers [4]. In the same way, Gleason pattern 3 glands exhibit infiltrative growth by extending between benign glands, invading nerves, and sometimes extending outside of the prostate. This difference in mindset regarding some types of “cancers” could be considered supportive evidence for the assertion in the recent Melbourne Consensus Statement that uncoupling prostate cancer diagnosis from intervention may be more appropriate than removing its “cancer” nomenclature.


This small GS6 adenocarcinoma was an incidental finding in a radical cystoprostatectomy specimen for bladder cancer but surprisingly extended into periprostatic fat via this focus of perineural invasion.

Supporting removal of the cancer designation from some prostatic adenocarcinomas:

A valid argument of the NCI Viewpoint is that a neoplasm should have a substantive rate of progression and patient death if it is to be considered a cancer. Likewise, others have questioned whether low-volume GS6 tumors fulfill other molecular and pathogenetic hallmarks of cancer, such as unlimited replicative potential and other features [5].

In general, benign and malignant neoplasms can be regarded as having some prototypical gross and microscopic pathologic characteristics, such as a circumscribed vs infiltrative growth and homogeneous vs pleomorphic cell population. However, differentiating benign from malignant lesions also relies heavily on parameters specific to the organ involved. Clear cell renal cell carcinoma, another genitourinary tract tumor, often does not possess these prototypical features of malignancy. Tumors often form a well-circumscribed mass without an “invasive” growth pattern and they often are composed of a uniform population of cells. However, based on known behavior of these tumors, their status as a malignancy is not in doubt. Conversely, renal oncocytoma is a benign neoplasm that shares some of these general features (a round mass composed of a homogeneous population of renal tubular cells). Occasionally oncocytomas appear infiltrative by extending into the perinephric fat or renal vein, yet their status as benign is also not the subject of debate. If some prostate cancers do not have a substantial likelihood of resulting in progression and death, they may not meet an important criterion for a diagnosis of cancer, despite that other features, such as infiltration of tissues, invasion of nerves, and loss of the basal cell layer are characteristic of a malignant neoplasm.

Since a diagnosis of GS6 by needle biopsy is not always predictive of a radical prostatectomy overall GS6, a major challenge to such an approach would be to determine where such a cutoff could be drawn between “cancer” and “not cancer” [5]. If based on tumor volume, it would be difficult to conceptualize that a small amount of GS6 glands would be regarded as a benign lesion, whereas a large amount of identical glands would represent a malignant lesion. Alternatively, the presence of Gleason pattern 4 could used as the point of differentiation (GS7 or above). In the endometrium, a disorganized proliferation of crowded glands with some cytologic features of cancer is regarded as complex atypical hyperplasia. Diagnosis of adenocarcinoma is then reserved for proliferations with a confluent growth of these glands, similar to the threshold for recognizing a component of cribriform glands as Gleason pattern 4. A limitation to such an approach, however, is that a substantial fraction of patients with a needle biopsy GS6 are upgraded to GS7 at radical prostatectomy, as discussed above. Likewise, the ability to treat and monitor GS6 adenocarcinoma nonsurgically is not quite analogous to that of endometrial hyperplasia.

Higher magnification of image 2 shows Gleason pattern 3 glands invading a nerve with ganglion cells.

Other points of discussion

The NCI Viewpoint also suggests that high-grade prostatic intraepithelial neoplasia (HGPIN) no longer be considered cancer or even neoplasia.  A comparison to ductal carcinoma in situ (DCIS) of the breast for this argument is somewhat flawed, as HGPIN neither contains the word “carcinoma” nor is justification for treatment in and of itself. Its status as a risk factor for a future cancer even remains debated. The proposal to remove “neoplasia” from HGPIN is also a confusing one, particularly as cervical cancer is noted as an example of the successful application of screening, in which “cervical intraepithelial neoplasia” is the preferred term for precancerous lesions. The authors suggest the designation “indolent lesions of epithelial origin” (IDLE) for cancers in this category to convey their low likelihood of aggressive behavior. However, would recognizing the status of these lesions as at least premalignant neoplasms be more appropriate?

Likely a typographical error in the Viewpoint is that the authors also cite reclassification of urothelial papilloma as papillary urothelial neoplasm of low malignant potential [1]. Since urothelial papilloma has never been considered a malignant neoplasm, the authors likely meant reclassifying “grade 1 urothelial carcinoma” to papillary urothelial neoplasm of low malignant potential.

References
[1]        Esserman LJ, Thompson IM, Reid B. Overdiagnosis and Overtreatment in Cancer: An Opportunity for Improvement. JAMA. 2013 Jul 29:

[2]        Epstein JI, Allsbrook WC, Jr., Amin MB, Egevad LL. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005 Sep: 29:1228-42

[3]        Carter HB, Partin AW, Walsh PC, et al. Gleason score 6 adenocarcinoma: should it be labeled as cancer? J Clin Oncol. 2012 Dec 10: 30:4294-6

[4]        Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan: 63:11-30

[5]        Ahmed HU, Arya M, Freeman A, Emberton M. Do low-grade and low-volume prostate cancers bear the hallmarks of malignancy? Lancet Oncol. 2012 Nov: 13:e509-17

 

Sean Williamson is Senior Staff Pathologist in the Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit MI, USA. @Williamson_SR

Tiger Testes

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Although I enjoyed reading Jim Duthie’s Blog Post ‘Surgery Isn’t Normal’, I would argue that no profession, particularly those constituting a high degree of specialization, are normal. Let me set the scene from a research scientist’s perspective…

It was late on a Tuesday night three years ago, and being a poor PhD student at the time (PhD scholarships pay below poverty level), I was completing my part-time work in the histology department to help make the rent. My research laboratory specialises in diseases of the prostate; however, the laboratory next to ours – for which I was currently performing histology work – specialises in germ cell development and male fertility. Most of their work is focused on the human species, however, one of their projects was looking into the fertility of rare or endangered species to help prevent their extinction. As such, they had an ethics agreement with the Melbourne Zoo which gave them access to the reproductive organs of any endangered species that passed away. So there I was on my microtome sectioning the testes of a recently deceased Bengal tiger.

For anyone who works in pathology, the temperature and hydration of tissue to be sectioned must stay within a tight range in order to obtain perfect 5-µM thick sections that can then be stained for analysis. Too hot and your tissue will crumple, too cold and the sections will curl over on themselves, whilst over-hydrated tissues will swell out of the paraffin wax, and under-hydrated tissues break when they meet the microtome’s blade. These tiger testes were getting a little too warm for my liking, so I placed them on ice and left the room to grab myself a beverage from the hospital cafe – cutting testes is thirsty work!

To my dismay when I arrived back at the hospital laboratory my access card would not let me in the room. It was late, no one was around in the histology department, and I was now getting worried about the time these testes had been sitting in water on ice, so I headed for the hospital security. As I stood there explaining to a ICORP Security guard that I urgently needed to get into the histology department on level 3 as my tiger testes were getting too cold and may over hydrate, I too had the realisation of how abnormal this must seem. And yet, the very things that may make my job seem abnormal to an outsider are the very things I love most about my role. Every day is different, and I get exposed to new and exciting research projects that really make a difference to the world and people in it.

This particular job has also come in handy in some unexpected situations. When I caught a man trying to steal the hubcaps off my tyres I was able to tell him, “I may look harmless, but I cut testes for a living,” and so my hubcaps remain…

Dr Sarah Wilkinson is a post-doctoral research fellow at Monash University, Melbourne. She is interested in how the prostate tumour microenvironment can be targeted as a therapeutic treatment for prostate cancer.

Twitter: @wilko3040

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