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RE: Outcomes of high complex renal tumor (PADUA ≥ 10) following robot-assisted partial nephrectomy with a median 46 months follow-up: A tertiary center experience

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Letter to the Editor

Outcomes of high complex renal tumor (PADUA ≥ 10) following robot-assisted partial nephrectomy with a median 46 months follow-up: A tertiary center experience

Sir,

We read this article by Raheem et al with great interest and appreciate the efforts of the authors to publish the largest single centre data on outcomes of high complexity tumors with PADUA score>10 [1]. We wish to highlight a few points. In table 1 the T stage classification has been applied to all the tumors irrespective of their benign or malignant nature. The AJCC TNM classification is particularly meant to stage renal cell carcinomas which are histopathologically proven [2].

It is clear from table 1 itself that there are 36 patients of Angiomyolipomas (AML) in the series which have erroneously been assigned a T stage and that it is likely that there may be other benign pathology in the patient cohort which might need to be de-staged once the pathology is available. Although this redistribution of staging might not affect the results, it is necessary so that the readers are not given a false impression of it being the same as well as to prevent the reproduction of such errors in future studies. A better way to categorize this can be seen in the study by Ficcara et al with benign tumors being categorized separately [3].

Another point of contention is that Fuhrman grading in table 1 has been applied to all the malignant tumors. For example in low PADUA score groups the total number of patients having Fuhrman grading is 52 while the number of patients with clear cell carcinoma is 42 with others being 5 in numbers. AML, papillary and chromphobe make up 25/72 tumors. It is known from the available literature that Fuhrman grading is only applied to clear cell carcinoma and its variants while Chromophobe carcinoma or papillary carcinoma is not graded by Fuhrman’s grading [4,5]. These points might not affect the basic theme of the study but are worth consideration.

Aditya Prakash Sharma. MBBS, MS

Senior Resident (M.Ch.), Department of Urology , PGIMER, Chandigarh

Girdhar S Bora, MS,M.Ch

Assistant professor, Department of Urology , PGIMER, Chandigarh

Ravimohan S Mavuduru, MS, M.Ch.

Associate Professor, Department of Urology , PGIMER, Chandigarh

Arup Kumar Mandal, MS, M.Ch.

Professor, Department of Urology, PGIMER, Chandigarh

References

  1. Abdel Raheem A, Alatawi A, Kim DK, Sheikh A, Alabdulaali I, Han WK, Choi YD, Rha KH. Outcomes of high-complexity renal tumours with a Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score of ≥10 after robot-assisted partial nephrectomy with a median 46.5-month follow-up: a tertiary centre experience. BJU Int. 2016 Apr 22. doi: 10.1111/bju.13501. [Epub ahead of print]
  2. Guinan, P., Sobin, LH, Algaba, F., Badellino, F., Kameyama, S., MacLennan, G. and Novick,  A.(1997), TNM staging of renal cell carcinoma. Cancer, 80: 992–993
  3. Ficarra V, Novara G, Secco S, Macchi V, Porzionato A, De Caro R, Artibani W. Preoperative aspects and dimensions used for an anatomical (PADUA) classification of renal tumours in patients who are candidates for nephron-sparing surgery. Eur Urol. 2009 Nov;56(5):786-93.
  4. Delahunt B. Advances and controversies in grading and staging of renal cell carcinoma. Mod Pathol. 2009 Jun;22 Suppl 2:S24-36
  5. Sika-Paotonu D1, Bethwaite PB, McCredie MR, William Jordan T, Delahunt B. Nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. Am J Surg Pathol. 2006 Sep;30(9):1091-6.

 

 

 

Reply by the authors

We would like to thank the authors for their interest in reading our manuscript discussing the outcomes of high-complex PADUA renal tumors following robot-assisted partial nephrectomy (RAPN) [1]. We admit the discordance after pathological confirmation of benign and malignant nature of the masses and its need to be de-staged and revisited.

The main primary outcome of our study was to assess trifecta achievement and its predictors; meanwhile, the secondary end point was oncological safety and functional outcomes evaluation in patients with high-complex PADUA renal tumors. Notably, trifecta “i.e. WIT of <25 min, negative surgical margins and no and absence of perioperative complications” [2] does not incorporate long-term outcomes assessment after partial nephrectomy surgery; however, it provides us with an important data about the intraoperative surgical quality and efficiency, and early postoperative morbidity. PADUA classification is based on ‘preoperative radiological scoring of the renal masses’ and is applied for both benign and malignant masses [3].

In the current study, the majority of high-complex PADUA masses were malignant, and this group showed significant increase in conversion to radical nephrectomy, more perioperative morbidities, median WIT of 26 min; and subsequently, had a lower rate of trifecta achievement [1]. Previously, we reported excellent perioperative outcomes of angiomyolipoma (AML) after RAPN [4].  There were no intraoperative complications or blood transfusion. Moreover, WIT was short (median 19.5 min) [4]. Additionally, the long-term outcomes, AML has been proven to have good postoperative renal function preservation and no local recurrence after RAPN [4]. Putting in consideration the abovementioned results, it is apparent that inclusion of benign masses will not affect the outcomes.

 

Ali Abdel Raheem†*, Atalla Alatawi*, Dae Keun Kim¥, Abulhasan Sheikh*, Ibrahim Alabdulaali*, Woong Kyu Han*, Young Deuk Choi*, and Koon Ho Rha*

*Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, South Korea

†Department of Urology, Tanta University Medical School, Egypt

¥Department of Urology, CHA Seoul Station Medical Center, CHA University Medical School, Seoul, Republic of Korea

 

 References

  1. Abdel Raheem A, Alatawi A, Kim DK, et al. Outcomes of high-complexity renal tumours with a Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score of ≥10 after robot-assisted partial nephrectomy with a median 46.5-month follow-up: a tertiary centre experience. BJU Int. 2016 Apr 22. doi: 10.1111/bju.13501. [Epub ahead of print]
  2. Ficarra V, Novara G, Secco S et al. Perioperative aspects and dimensions used for an anatomical (PADUA) classification of renal tumours in patients who are candidates for nephron-sparing surgery. Eur Urol 2009;56: 786–93
  3. Khalifeh A, Autorino R, Hillyer SP et al. Comparative outcomes and assessment of trifecta in 500 robotic and laparoscopic partial nephrectomy cases: a single surgeon experience. J Urol 2013; 189: 1236–42
  4. Abdel Raheem A and Rha KH. RE: Robotic Partial Nephrectomy in the Treatment of Renal Angiomyolipomas. J Endourol.2016 Apr 15. [Epub ahead of print]

 

RE: Opportunity of widening the resort to multiparametric MRI/transrectal ultrasound fusion imaging-guided prostate cancer brachytherapy

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Sir,

Thank you for your interest in our article regarding whole-gland brachytherapy to the prostate for prostate cancer (1). Your letter is highlighting the expanding role of brachytherapy to that of focal therapy (2). We agree that multiparametric magnetic resonance imaging (mpMRI) scans have expanded the ability to localise tumours and indeed that they may be useful in carefully selected men wishing to undergo focal therapy. However, other  advances such as the use of fiducial markers and spacers have also allowed better dosimetry and for a reduction in side effects (3).  The safety and performance of brachytherapy in whole gland treatment means we should have faith in it as a modality to destroy cancer on the focal therapy setting. There are new trials being developed with focal brachytherapy and we look forward to the results in the coming years.

 

References

  1. Chao MW, Grimm P, Yaxley J, Jagavkar R, Ng M, Lawrentschuk N. Brachytherapy: state-of-the-art radiotherapy in prostate cancer. BJU Int  2015; 116(S3): 80-8. doi: 10.1111/bju.13252.
  1. Nguyen PL, Trachtenberg J, Polascik TJ. The role of focal therapy in the management of localised prostate cancer: a systematic review. Eur Urol. 2014 Oct;66(4):732-51. doi: 10.1016/j.eururo.2013.05.048. Epub 2013 Jun 6. Review.
  1. Ng M1, Brown E, Williams A, Chao M, Lawrentschuk N, Chee R. BJU Int. 2014 Mar;113 Suppl 2:13-20. doi: 10.1111/bju.12624. Fiducial markers and spacers in prostate radiotherapy: current applications.

 

 

Letter to the Editor

Opportunity of widening the resort to multiparametric MRI/transrectal ultrasound fusion imaging-guided prostate cancer brachytherapy  

Sir,

I have recently read, with high interest, the review article “Brachytherapy: state-of-the-art radiotherapy in prostate cancer”, by Chao et al.[1].  The authors made extremely clear the advanced technologies of computerized treatment planning and imaging-guided delivery modalities to reach a tailored ablative prostate tumor target dose by resorting to either low-dose-rate (LDR) or high-dose-rate (HDR) different brachytherapy procedures as regards three basic – low, intermediate, high – disease risk classificative conditions.   

It is today proven that focal instrumental procedures inside the prostate gland – from biopsy to various prostate cancer focused ablative strategies, among which laser interstitial thermal therapy and particularly the prostate cancer brachytherapy – might require the resort to proper software digital overlay-mediated fusion of both beforehand multiparametric magnetic resonance imaging (mpMRI) scans and later real-time transrectal 3D ultrasound findings.  Like this, indeed, intriguing developments  in software modelling techniques have led to reach, by a mpMRI-ultrasound image fusion approach, more accurate targeted prostate cancer biopsies than those by transrectal ultrasound imaging alone achieved [2,3].

If the transperineal focal laser prostate tumor ablation  usually occurs only with the guidance of mpMRI (T2-weighted, diffusion-weighted, dynamic contrast material) [4], as regards the prostate cancer brachytherapy, instead, it is more and more timely, for just targeting the tumor “index-dominant lesion”, the resort to mpMRI/transrectal real-time ultrasound fusion imaging.  Quite recently, mpMRI/real-time transrectal ultrasound software-mediated digital co-registration has allowed to properly carry-out, in patients suffering from intermediate/high risk prostate carcinoma with mpMRI visible “index- dominant” intraprostatic nodule, the HDR ¹⁹² Ir transperineal temporary implant-brachytherapy  as accurate partial prostate radiation dose escalation supplemental to hypofractionated external beam radiotherapy [5,6].   

Given the interesting, even rare, reports on this subject, it would be advisable to widen the resort to the above-outlined mpMRI/transrectal  ultrasound fusion imaging-guided prostate cancer brachytherapy, particularly for a suitably targeted dominant tumor nodule detection/ablation.

 

Contardo Alberti

L D of Surgical Semeiotics, University of Parma, Parma, Italy

 

 References

1  Chao MW, Grimm P, Yaxley J, Jagavkar R, Ng M, Lawrentschuk N. Brachytherapy: state-of-the-art radiotherapy in prostate cancer. BJU Int  2015; 116(S3): 80-8. doi: 10.1111/bju.13252.

2  Shoji S, Hiraiwa S, Endo J, Hashida K, Tomonaga T, Nakano M et al. Manually controlled targeted prostate biopsy with real-time fusion imaging of multiparametric magnetic resonance imaging and stransrectal ulrasound :an early experience. Int J Urol 2015; 22(2): 173-8. doi: 10.1111/iju.12643.

 3  Marks L, Young S, Natarajan S.  MRI-ultrasound fusion for guidance of targeted prostate biopsy. Curr Opin Urol 2013; 23(1): 43-50. doi: 10.1097/MOU.0b013e32835ad3ee.

4  Woodrum DA, Kawashima A, Gorny KR, Mynderse LA. Magnetic resonance-guided thermal therapy for localized and recurrent prostate cancer. Magn Reson Imaging Clin N Am.2015; 23(4): 607-19. doi:10.1016/j.mric.2015.05.014

5  Bubley GJ, Bloch BN, Vazquez C, Genega E, Holupka E, Rofsky N, Kaplan I.  Accuracy of endorectal magnetic resonance/transrectal ultrasound fusion for detection of prostate cancer during brachytherapy. Urology 2013;81(6): 1284-9. doi: 10.1016/j.urology.2012.12.051.

6  Gomez-Iturriaga A, Casquero F, Urresola A, Ezquerro A, Lopez JI, Espinosa JM et al. Dose escalation to dominant intraprostatic lesions with MRI-transrectal  ultrasound fusion high-dode-rate prostate brachytherapy. Radiother Oncol 2016 Feb 15. doi: 10.1016/j.radonc.2016.02.004 (Epub ahead of print).

 

RE: Prostate Carcinoma With Positive Margins at Radical Prostatectomy: Role of Tumour Zonal Origin in Biochemical Recurrence

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Sir,

With great interest, we read the recent article by O’Neil et al. [1], in which the authors investigated the relation between the tumour zonal origin (transition zone vs peripheral zone), positive surgical margins (PSM) after radical prostatectomy and the risk of biochemical recurrence (BCR). Clinicopathological data for 323 patients with PSM after prostatectomy were analysed, of which tumours arising in the prostate transition zone (TZ) were 13%, while tumours in the peripheral zone (PZ) were 87%. The data showed that the percentage of PSM was higher for TZ compared with PZ tumours, with frequent involvement of the bladder neck margins for TZ tumours, without significant difference in time to BCR. In this cohort of patients, adjuvant radiotherapy (ART) was performed in 41% and 53% of TZ and PZ tumours, respectively. Contrary to expectation, BCR was earlier and at higher rate in patients who underwent radiotherapy for TZ rather than PZ tumours.

In the authors’ opinion, these data represent a selection bias, probably due to the higher incidence of bladder neck positive margins in the ART group. This is a novel finding that warrants further investigation.

As radiation oncologists, we make the following comments:

ART is recommended in patients with adverse pathologic features in order to reduce the risk of BCR, local recurrence and clinical progression [2]. Despite the use of a multimodal approach for radiotherapy planning, approximately 40% of patients experienced BCR long-term with an higher risk of developing metastases or cancer-related death [3,4]. It is plausible that the reasons of local failure may include inadequate radiation dose and target coverage, particularly at the anastomotic site, and this probably represents another bias to be considered as well as patient selection, as suggested by O’Neil and colleagues. To date, four different guidelines for clinical target volume (CTV) delineation in the post-prostatectomy setting are available, although there is little data to guide radiation oncologists on appropriate margins selection [5]. The proposed CTVs differed significantly among these consensus guidelines with respect to target border, especially in anterior and cranial directions. In particular, the European Organization for Research and Treatment of Cancer (EORTC) CTV was smaller in comparison with other consensus volumes, with more limited prostate bed coverage and with less irradiation of surrounding healthy tissue, to reduce radiation therapy side effects[5].

In our opinion, for the majority of cancer patients to be treated effectively, the risk of marginal misses is greater than normal tissue complications, and could affect the clinical outcome; thus, target coverage should generally not be compromised [6]. We would also like to add that small treatment margins may be more sensitive to geometrical uncertainties, including set-up errors and inter- and intra-fraction target motions of the prostate bed, and daily image guidance is required [7]. Finally, we believe that to make definitive recommendations regarding the magnitude of margin reduction with improvement of therapeutic ratio, an accurate selection of patients is required.

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Maria Grazia Ruo Redda1 MD, Alessia Reali1 MD, Roberta Verna1 MD, and Simona Allis1 MD.

1Department of Oncology, Radiation Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano, Turin, Italy.

References

  1. O’Neil LM, Walsh S, Cohen RJ, Lee S. Prostate carcinoma with positive margins at radical prostatectomy: role of tumour zonal origin in biochemical recurrence. BJUI 2015, Jul 27. [Epub ahead of print]

    2.  

  2. Thompson IM, Valicenti RK, Albertsen P, et al. Adjuvant and Salvage Radiotherapy after Prostatectomy: AUA/ASTRO Guideline. J Urol 2013;190:441-9.

    3.  

  3. Bolla M, van Poppel H, Tombal B, et al. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet 2012;380:2018-27.

    4.  

  4. Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long term follow-up of arandomized trial. J Urol 2009;181:956–62.

    5.  

  5. Malone S, Croke J, Roustan-Delatour N, et al. Postoperative radiotherapy for prostate cancer: a comparison of four consensus guidelines and dosimetric evaluation of 3D-CRT versus tomotherapy IMRT. Int J Radiat Oncol Biol Phys 2012;84:725-32.

    6.  

  6. Marks LB, Yorke ED, Jackson A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 2010;76(3):S10-9.

    7.  

  7. Gill S, Isiah R, Adams R, et al. Conventional margins not sufficient for post-prostatectomy prostate bed coverage: An analysis of 477 cone-beam computed tomography scans. Radiother Oncol 2014 Feb;110(2):235-9.

    8.  

RE: In patients with a previous negative prostate biopsy and a suspicious lesion on magnetic resonance imaging, is a 12-core biopsy still necessary in addition to a targeted biopsy?

/1 Comment/by

Sir,

We read with much interest the work of Salami [1], which strengthens the evidence in favour of a mpMRI targeted biopsy (TBx) in the diagnostic work-up of patients with persistent clinical suspicion of prostate cancer (PCa). TBx can indeed improve the detection rate of prostate biopsy  without the need of a systematic sampling, especially in presence of previous negative histological findings [2]. TBx might also reduce the risk of biopsy-related complications, as much as improve patient quality of life, focusing only on suspicious mpMRI targets. Thanks to the high negative predictive value of mpMRI [2], patients with persistently high PSA could even avoid the re-biopsy, in presence of a negative mpMRI. In this light, probably TBx should be implemented by current guidelines in the re-biopsy setting not only as a ‘’possible option’’, but as a recommendation.

But is it really safe to avoid random biopsies and restrict to index lesion targeting? According to recent evidence, systematic sampling does not significantly improve the detection rate, at least in terms of clinically significant PCa [2, 3]. A recent trial published on JAMA deposed against systematic sampling, showing that 17 low-risk diagnoses are needed to find a high-risk PCa by adding systematic sampling to TBx [3]. The added value of this trial was that the urologist performing systematic biopsies was blinded to mpMRI. In the study by Salami, instead, random sampling was “cognitive”, as the urologist knew the location of the lesions at mpMRI, possibly causing a falsely higher detection rate of standard biopsies. These findings confirm that the space for random biopsies is narrowing, as compared to TBx.

Although mpMRI has achieved an important role in early PCa detection, several issues still need to be investigated to reach a complete understanding of its diagnostic potential. First, the heterogeneity in MRI technical features and imaging analyses possibly hamper the comparison of mpMRI outcomes and its generalization to clinical practice [4]. Secondly, the variability in the assessment of PCa clinical significance represents another bias, considering that mpMRI series usually use biopsies as terms of comparison to assess mpMRI accuracy, instead of radical prostatectomy specimens. This is an important limitation, as Gleason score upgrading from biopsy to radical prostatectomy has been reported in about 30% of patients [5], changing the rules of risk attribution. No consensus has been reached about the definition itself of PCa clinical significance. Thirdly, further evidence is required to assess the number of cores that need to be taken for TBx in order to obtain a reliable sampling. A final aspect to be considered involves the possibility of procedural errors and a certain degree of mpMRI inaccuracy, as shown by some significant PCa detected in spite of a negative TBx [1]. We are confident, though, that some of this inaccuracy will disappear with the progression in the learning curve, both on urological and radiological sides.

Although the evidence on mpMRI and TBx is increasing, further studies are advised to shed light on these aspects that remain not fully understood, before giving a final recommendation on this topic.

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Marco Oderda, Giancarlo Marra, Paolo Gontero

Department of Urology, San Giovanni Battista Hospital, University of Turin, Città della Salute e della Scienza, Turin, Italy

 

Source of Funding: Giancarlo Marra is funded by the Fondazione di Ricerca Molinette Onlus

 

Conflict of Interest: None.

References

[1]          Salami SS, Ben-Levi E, Yaskiv O, et al. In patients with a previous negative prostate biopsy and a suspicious lesion on magnetic resonance imaging, is a 12-core biopsy still necessary in addition to a targeted biopsy? BJU international. 2015 Apr: 115:562-70

[2]          Schoots IG, Roobol MJ, Nieboer D, Bangma CH, Steyerberg EW, Hunink MG. Magnetic Resonance Imaging-targeted Biopsy May Enhance the Diagnostic Accuracy of Significant Prostate Cancer Detection Compared to Standard Transrectal Ultrasound-guided Biopsy: A Systematic Review and Meta-analysis. European urology. 2014 Dec 2:

[3]          Siddiqui MM, Rais-Bahrami S, Turkbey B, et al. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. Jama. 2015 Jan 27: 313:390-7

[4]          Futterer JJ, Briganti A, De Visschere P, et al. Can Clinically Significant Prostate Cancer Be Detected with Multiparametric Magnetic Resonance Imaging? A Systematic Review of the Literature. European urology. 2015 Feb 2:

[5]          Cohen MS, Hanley RS, Kurteva T, et al. Comparing the Gleason prostate biopsy and Gleason prostatectomy grading system: the Lahey Clinic Medical Center experience and an international meta-analysis. European urology. 2008 Aug: 54:371-81

 

Cumulative cancer length in selecting candidates for Active Surveillance: use or abuse?

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Sir,

Chen et al. [1] have performed an interesting evaluation on  cumulative cancer length on prostate needle biopsy (Bx) divided by the number of biopsy cores (CCL/core) in predicting outcomes after radical prostatectomy (RP) in candidates for Active Surveillance (AS). Criticisms against AS criteria could concern the relevant proportion of upstaging, upgrading or unfavourable cancer in subjects with apparently low- or favourable-risk PCa [2].

To this regard, AS has gained popularity with the intention of avoiding or postponing interventions in subjects with PCa of low biological potential. Characteristics of AS protocols are the use of serum prostate-specific antigen (PSA) measurement, clinical evaluation through performance status and digital rectal examination, magnetic resonance imaging analysis and pathologic bioptical examination. In this multidisciplinary setting, it is obvious that although AS could benefit some patients, the risk of misclassification still persist in others. In the updated results from the Prostate Cancer Research International: Active Surveillance (PRIAS) study, 27% of the cohort experienced disease reclassification (defined as Gleason score >6 and/or more than positive cores) at repeated biopsy during follow-up [3].

According to a recent comparison of several contemporary protocols, the PRIAS study showed the highest ability to identify patients with organ-confined low-grade cancer, with an AUC of 0.62 [4].

In this context, various morphometric measurements of cancer extent on needle prostatic biopsies have been proposed in order to improve selection for AS and RP outcomes may provide a surrogate for protocol performance.

Efforts are currently being made by researchers to optimize selection criteria, expand indications, and search for accurate tools that may help reduce the initial misclassification of aggressive disease. One of the most easily obtainable measurements of biopsy tumor extent is the CCL, or similarly the CCL/core, as a new pathological feature of prostate biopsy [5]. In the study by Chen et al. [1], a cut-off of CCL/core ≥0.20 mm was significantly associated with insignificant cancer at the univariate logistic regression analysis but not at the multivariate. CCL/core ≥0.20 mm was found to be associated with low-volume organ-confined disease (LV-OCD) defined as pT2 PCa with RP Gleason score ≤ 3+4=7 and volume <0.5 mL.

However there could be a bias in either the enrolment of patients with Bx Gleason score ≤ 3+4=7 (not eligible for current AS protocols) or insufficient of validation of the AS criteria applied.

It should be noted that different criteria have been used to define “unfavourable” disease, but a Gleason score of 7 may represent a “significant” cancer.

Moreover, if a potential predictive factor may be considered potentially efficient, it should improve a pre-existing model and be compared to it. To this regard, although not statistically demonstrated by receiver operating curve analysis, the accuracy of the model for predicting LC-OCD (using number of positive cores 1 vs. 2, Max % core involvement <50, and CCL/core <0.20 mm) in patients with Bx Gleason score 3+3=6 was lower than model not using CCL/core <0.20 mm).

In a recent article that we published, we demonstrated that adding to PRIAS criteria the percentage of cancer involvement in positive cores (CIPC) ≥ 0.4 mm, calculated by dividing the cumulative cancer length (CCL) to the cumulative length of positive cores (CLPC), significantly improved the ROC analysis from 0.61 to 0.94 [6].

Before suggesting current AS protocol to include CCL to the criteria we would offer some suggestions. First of all, differences still exist about its definition. We would underline that dividing the CCL to the cumulative length of positive cancer, defined as CIPC, and not to the number of biopsy cores, could be more suitable for identifying a significant PCa, due to its better “mathematical” definition.

Furthermore, observational protocol-based AS studies may be more helpful by analyzing the risk of misclassification at the second biopsy and by comparing CIPC and CCL/core. We can officially give the acceptance of CCL/core or CIPC only consolidating the AS criteria and the definition of “significant” PCa.

At this time we do not discourage patients from AS until CCL use or abuse is unveiled.

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Conflict of Interest
None declared

Giorgio Ivan Russo1*, Giuseppe Morgia1
1Department of Urology, University of Catania, Italy

*Correspondence: Dr. Giorgio Ivan Russo, M.D., Department of Urology, University of Catania, Italy.
Tel.  +39 (95) 3782712;  fax +39 (95) 3782373; e-mail: [email protected]

References

  1. Chen DJ, Falzarano SM, McKenney JK, et al. Does cumulative prostate cancer length in prostate biopsies improve prediction of clinically insignificant cancer at radical prostatectomy in patients eligible for active surveillance? BJU Int 2014; doi: 10.1111/bju.12880
  2. Kates M, Tosoian JJ, Trock BJ, Feng Z, Carter HB, Partin AW. Indications for intervention during active surveillance of prostate cancer: a comparison of the Johns Hopkins and Prostate Cancer Research International Active Surveillance (PRIAS) protocols. BJU Int 2014; doi: 10.1111/bju.12828
  3. Bul M, Zhu X, Valdagni R, et al. Active surveillance for low-risk prostate cancer worldwide: the PRIAS study. Eur Urol 2013; 63: 597-603
  4. Iremashvili V, Pelaez L, Manoharan M, Jorda M, Rosenberg DL, Soloway MS. Pathologic prostate cancer characteristics in patients eligible for active surveillance: a head-to-head comparison of contemporary protocols. Eur Urol 2012; 62: 462-8
  5. Komai Y, Kawakami S, Numao N, et al. Extended biopsy based criteria incorporating cumulative cancer length for predicting clinically insignificant prostate cancer. BJU Int 2012; 110: E564-9
  6. Russo GI, Cimino S, Castelli T, et al. Percentage of cancer involvement in positive cores can predict unfavorable disease in men with low-risk prostate cancer but eligible for the prostate cancer international: active surveillance criteria. Urol Oncol 2014; 32: 291-6

 

Re: New surgical technique for ventral penile curvature without circumcision

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Sir, 

While the dual concept of operating via an infrapubic incision and using a “double breasted” tunical repair technique for ventral penile curvature is interesting, Alei et al. make a number of statements which must be challenged [1].

  1. We would concur that discussion and documentation of penile length is vital prior to surgery for penile curvature, particularly to reduce medicolegal risk. The demonstration and advice described is vital, particularly before Peyronie’s disease surgery where the plaque itself is the shortening agent and the patient directly compares his pre- and post-operative appearance. However, in our experience, men seeking congenital curvature correction rarely have an issue with post-operative shortening complaints – indeed a ventrally curved penis when straightened may actually look longer from the patient’s viewpoint.
  2. To suggest that this technique causes less shortening than other techniques is counterintuitive, and without evidence. To achieve complete penile straightening by any technique, the ventral, dorsal and lateral measurements must be equal. Therefore, how can one technique cause less shortening?
  3. Stating that the described technique is “far superior” to other published papers cannot in any way be justified as this is a single-centre series with no controls.
  4. Lastly the description of a “tiny surgical breach” seems to refer to a 5cm infrapubic incision – not so tiny. In any case, such incisions when used with “penile enhancement” surgery are frequently complicated by oedema and keloid scarring [2], so it should not be automatically assumed that this incision will be of minimal morbidity.

Whilst applauding the desire to minimise morbidity we would suggest further comparative studies to fully evaluate the new technique, and possibly less hyperbole in describing a case series.

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Paul Sturch and Gordon Muir
Urology Department, King’s College Hospital, London, UK
e-mail: [email protected], [email protected]

References

  1. Alei G, Letizia P, Alei L, Massoni F, Ricci S. New surgical technique for ventral penile curvature without circumcision. BJU Int 2014; 113: 968-74
  2. Wessells H, Lue TF, McAninch JW. Complications of penile lengthening and augmentation seen at 1 referral center. J Urol 1996; 155: 1617-20

 

Prostate cancer survivorship and psychosexual function: a silent epidemic

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Sir,

We were delighted to read the comment by Vasdev et al. [1]. This is an important topic relating to prostate cancer survivorship which is currently unaddressed.

One of the problems survivors encounter post-therapy is psychosexual concerns [2]. These are critical to manage appropriately. With individualised treatment options, survivors may be able to gain a significant improvement in sexual function. In addition, a reduction in quality-of-life is related to sexual dysfunction after completing cancer treatment [3]. A study found that survivors report being significantly concerned about sexual function, yet few seek help for sexual problems [4].

Men who have undergone radical prostatectomy experience greater stress on relationships than men receiving external beam radiation therapy, perhaps due to the fact that they are younger. Younger men have greater concerns and are more sexually active. In two retrospective cohort studies, men receiving nerve sparing surgery at age 39–54 were more likely than older men and men receiving non-nerve sparing surgery, to report erections firm enough for intercourse [5,6].

NICE guidance on prostate cancer requires sexual dysfunction to be addressed as part of survivorship care, with early access to services post-therapy [5]. Currently, this is not fully addressed in many centres. In addition it has been found that ‘more motivated’ patients experienced greater distress from their sexual dysfunction postoperatively [7].

Postoperative management of patients who have had radical therapy for prostate cancer should take the patients’ individualised psychosexual concerns into account [8].

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Goonewardene SS*, Young A**, Persad R***
*Guys Hospital, Kings College London, **Warwick Medical School, ***North Bristol NHS Trust

References

  1. Vasdev N, Hoyland K, Adshead JM. Is it still clinically and economically viable in the UK to prescribe vacuum erection devices for patients with erectile dysfunction after radical prostatectomy? BJU Int 2014; 113: 356-57
  2. Northouse LL, Mood DW, Schafenacker A, et al. Randomized clinical trial of a family intervention for prostate cancer patients and their spouses. Cancer 2007; 110: 2809-18
  3. Descazeaud A, Zerbib M, Hofer MD, Chaskalovic J, Debré B, Peyromaure M. Evolution of health-related quality of life two to seven years after retropubic radical prostatectomy: evaluation by UCLA prostate cancer index. World J Urol 2005; 23: 257-62
  4. Galbraith ME, Arechiga A, Ramirez J, Pedro LW. Prostate cancer survivors’ and partners’ self-reports of health-related quality of life, treatment symptoms, and marital satisfaction 2.5-5.5 years after treatment. Oncol Nurs Forum 2005; 32: E30-41
  5. Penson DF, McLerran D, Feng Z, et al. 5-Year urinary and sexual outcomes after radical prostatectomy: Results from the prostate cancer outcomes study. J Urol 2005; 173: 1701-05
  6. Sandblom G, Ladjevardi S, Garmo H, Varenhorst E. The impact of prostate-specific antigen level at diagnosis on the relative survival of 28,531 men with localized carcinoma of the prostate. Cancer 2008; 112: 813-9
  7. Song L, Northouse LL, Braun TM, et al. Assessing longitudinal quality of life in prostate cancer patients and their spouses: a multilevel modeling approach. Qual Life Res 2011; 20: 371-81
  8. Namiki S, Ishidoya S, Ito A, Arai Y. Abstract 671: The impact of sexual desire on sexual health related quality of life following radical prostatectomy: A 5-year follow up study in Japan. 27th Annual Congress of the European Association of Urology Eur Urol Suppl 2012; 11: e671

 

Multiparametric MRI – Is the result convincing for AS patients?

/by

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.

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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

 

Bladder cancer survivorship: orthotopic neobladders vs. ileal conduit, health economics in the way of progress

/1 Comment/by

Sir,

It is with optimism that we read your editorial on orthotopic neobladders (ONB) vs. ileal conduits (IC) [1] and also the articles by Singh et al. [2]  and Studer et al. [3].  Collectively, these are significant articles highlighting ONB as a preferable alternative to IC in terms of quality-of-life. The differences are even more pronounced where having an IC may be ‘censured’ in some parts of the world, perhaps for cultural reasons or practical/economic reasons, such as lack of availability of appliances.

We are aware that occasionally, for technical reasons or for reasons of patient choice (e.g. in the elderly) where a less complicated procedure is preferred for shorter operating time and a lower reoperation rate, ONB is not always desirable.

In the field of practice there are a number of issues we face. Firstly, despite an ageing population, there are a significant number of young patients with new bladder cancer diagnoses. This may be related to campaigns by the government regarding haematuria, giving greater awareness with earlier diagnoses [4]. Secondly, this sub-population of patients are more likely to be sexually active. As a result, many of these patients may not want an IC with urostomy. In particular, quality-of-life studies in the past [5] have indicated the severe psychosexual consequences of urostomies in younger patients and particularly in young women where body image is important for psychosexual wellbeing.

In this group, we would also include older more active patients who are physiologically and motivationally younger and who, for similar reasons, may not want an IC.  Surveys have been done across cancer networks (personal communication) indicating that for various reasons patients may not be in receipt of the choice of urinary diversion. In some centres, the perception is that there is a greater morbidity and even mortality from having ONB performed in comparison with IC. This is unfounded and may be promoted through ignorance or even preference of some CNS patient advocates whose experience may have been coloured by personal experience.

We would highlight a cost-effective aspect to this. We previously compared ileal conduits vs. orthotopic neobladders in 81 patients over 10 years. The cost of stoma management and pouches is approximately £1800 per patient per year [6]. Patients were sent home with 2190 stoma bags in total: approximately 27 per patient (range 10-70 bags). However if usage is excessive, this can increase to above £6000 per year for one patient [6].

If a patient does have an ONB, it immediately saves on cost of stoma care. In today’s financially constrained NHS, this may be an important consideration for trusts if we can avoid compromising patient care.  We are concerned however that due to the tariff costs for an ONB and ileal conduit being almost identical, there is incentive for more centres to do IC rather than ONB. With waiting list and breach pressures on all teams, this seems the logical financial option, however, it may not give the best outcome for the patient.

Training is an important issue. Cystectomies are only performed in major cancer centres and if ONB becomes less frequent or less ‘popular’, this could be detrimental to trainees’ exposure.

We propose DoH reconsider the tariff for ONB vs. IC, given that ONB is a longer, more complex procedure but potentially with improvements in both patient quality-of-life and significant savings on stoma care. We also suggest that (perhaps as an incorporated measure in Cancer Peer Review) patients who fit the profile for ONB should be counselled and offered this, in addition to IC, in an attempt to improve functional outcomes. As professionals, we should increase patient awareness of operative alternatives by involving support groups and organisations such as ABC (Action on Bladder Cancer). Lastly, trainees quite clearly need to be trained in both procedures and seek out these training opportunities if they wish to become cystectomists of the future.

Sanchia S. Goonewardene1, Adel Makar3, Raj Persad3
University of Warwick, 2Worcestershire Acute Hospitals, 3Southmead Hospital, Bristol

References

  1. Dasgupta P. Flying as high as a kite. BJU Int 2014; 113: 683
  2. Singh V, Yadav R, Sinha RJ, Gupta DK. Prospective comparison of quality-of-life outcomes between ileal conduit urinary diversion and orthotopic neobladder reconstruction after radical cystectomy: a statistical model. BJU Int 2014; 113: 726–732
  3. Studer UE. Life is good with orthotopic bladder substitutes! BJU Int 2014; 113: 686–687
  4. Cancer Research UK. The National Awareness and Early Diagnosis Initiative. Available at: https://www.cancerresearchuk.org/cancer-info/spotcancerearly/naedi/AboutNAEDI/. Accessed 22 April 2014
  5. Gerharz EW, Månsson A, Hunt S, Skinner EC, Månsson W. Quality of life after cystectomy and urinary diversion: an evidence based analysis. J Urol 2005;174: 1729-1736
  6. Stoma Care Nurses High Impact Steering Group. High Impact Actions for Stoma Care. Department of Health (DH), 2010.

 

Re: Effects of fluorescent light-guided transurethral resection on non-muscle-invasive bladder cancer: a systematic review and meta-analysis

/by

Sir,

In the field of non-muscle-invasive bladder cancer (NMIBC), accumulating data on hexaminolevulinate (HAL) or 5-aminolevulinic acid (5-ALA)-guided blue-light cystoscopy (BLC) show significant benefits over standard white-light cystoscopy (WLC) in terms of improved detection and reduced recurrence rates. A notable exception to this body of evidence is a meta-analysis published by Shen et al. in the BJUI in 2012 [1]. We have been puzzled by this discrepancy, which is at odds not only with our own experiences as long-term users of HAL and 5-ALA -guided BLC, but also with a more recent meta-analysis produced by the same department [2]. We therefore examined the paper by Shen et al. in order to better understand their conclusions and, in the process, identified a number of areas where the data reported in the meta‑analysis do not appear to match the figures in the original publications [3–16].

In particular, we are concerned that, where the original article reports detection and recurrence rates as percentages only, Shen et al. sometimes appear to calculate absolute numbers based on inappropriate denominators (e.g. an unselected patient population when the trial is about a specific subgroup), resulting in a dilution of the reported effect. In addition, on occasion, the BLC and WLC groups are transposed and recurrence rates are reported as recurrence-free survival rates. We provide a summary of the discrepancies that we have identified in Table 1.

Table 1: Potential data errors in the meta-analysis by Shen et al. [1] (discrepancies between the meta-analysis and original data highlighted in red)

We believe that these inconsistencies are likely to have a significant effect on the results of the meta‑analysis, as the authors find no significant difference in rates of tumour detection (including carcinoma in situ) or recurrence between BLC and WLC groups. We would like to emphasise that the conclusions that Shen et al. draw are in direct contrast to the general evidence base on HAL and 5-ALA-guided BLC. We are concerned that readers of the article by Shen et al. who have not seen the original papers may have a biased opinion of the value of BLC. We therefore respectfully request that you review the original publication and, if appropriate, publish an erratum covering any individual data discrepancies as well as the conclusions drawn from the meta-analysis.

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Marek Babjuk1*, Paolo Gontero2, Didier Jacqmin3, Alexander Karl4, Stephan Kruck5, Paramananthan Mariappan6, Juan Palou Redorta7, Arnulf Stenzl5, Roland van Velthoven8, J. Alfred Witjes9, Dirk Zaak10

1Department of Urology, 2nd Faculty of Medicine, Charles University in Prague, Motol Hospital, Prague, Czech Republic, 2Department of Urology, San Giovanni Battista Hospital, University of Turin, Turin, Italy, 3Department of Urology, Strasbourg University Hospital, Strasbourg, France, 4Department of Urology, Ludwig Maximilians University, Munich, Germany, 5Department of Urology, Eberhard Karls University, Tübingen, Germany, 6Department of Urology, Western General Hospital, Edinburgh, UK, 7Urologic Oncology Unit, Department of Urology, Puigvert Foundation, Barcelona, Spain, 8Department of Urology, Jules Bordet Institute, Brussels, Belgium, 9Department of Urology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands, and 10Department of Urology, Traunstein Hospital, Traunstein, Germany

*Corresponding author: Marek Babjuk, MD, PhD ([email protected])

Acknowledgement

The authors thank Succinct Medical Communications for editorial assistance in the meta-analysis data checking and preparation of this letter, with financial support from Ipsen SA. The authors retained editorial control over the content and the decision to submit this letter.

References

  3. Riedl CR, Daniltchenko D, Koenig F et al. Fluorescence endoscopy with 5-aminolevulinic acid reduces early recurrence rate in superficial bladder cancer. J Urol 2001; 165: 1121–1123
  16.  Drăgoescu O, Tomescu P, Pănuş A et al. Photodynamic diagnosis of non-muscle invasive bladder cancer using hexaminolevulinic acid. Rom J Morphol Embryol 2011; 52: 123–127

 

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