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Article of the Week: Perioperative and functional outcomes of elective RAPN for renal tumors with high surgical complexity

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.

Perioperative and renal functional outcomes of elective robot-assisted partial nephrectomy for renal tumors with high surgical complexity

Alessandro Volpe*†, Diletta Garrou*‡, Daniele Amparore*‡, Geert De Naeyer*, Francesco Porpiglia‡, Vincenzo Ficarra*§ and Alexandre Mottrie*

*Division of Urology, O.L.V. Vattikuti Robotic Surgery Institute, Aalst, Belgium, †Division of Urology, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, ‡Division of Urology, University of Torino, San Luigi Hospital, Orbassano, and §Division of Urology, University of Udine, Udine, Italy

OBJECTIVE

To evaluate the perioperative, postoperative and functional outcomes of robot-assisted partial nephrectomy (RAPN) for renal tumours with high surgical complexity at a large volume centre.

PATIENTS AND METHODS

Perioperative and functional outcomes of RAPNs for renal tumours with a Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score of ≥10 performed at our institution between September 2006 and December 2012 were collected in a prospectively maintained database and analysed. Surgical complications were graded according to the Clavien-Dindo classification. Serum creatinine and estimated glomerular filtration rate (eGFR) were assessed at the third postoperative day and 3–6 months after RAPN.

RESULTS

In all, 44 RAPNs for renal tumours with PADUA scores of ≥10 were included in the analysis; 23 tumours (52.3%) were cT1b. The median (interquartile range; range) operative time, estimated blood loss and warm ischaemia time (WIT) were 120 (94, 132; 60–230) min, 150 (80, 200; 25–1200) mL and 16 (13.8, 18; 5–35) min, respectively. Two intraoperative complications occurred (4.5%): one inferior vena caval injury and one bleed from the renal bed, which were both managed robotically. There were postoperative complications in 10 patients (22.7%), of whom four (9.1%) were high Clavien grade, including two bleeds that required percutaneous embolisation, one urinoma that resolved with ureteric stenting and one bowel occlusion managed with laparoscopic adhesiolysis. Two patients (4.5%) had positive surgical margins (PSMs) and were followed expectantly with no radiological recurrence at a mean follow-up of 23 months. The mean serum creatinine levels were significantly increased after surgery (121.1 vs 89.3 μmol/L; P = 0.001), but decreased over time, with no significant differences from the preoperative values at the 6-month follow-up (96.4 vs 89.3 μmol/L; P = 0.09). The same trend was seen for eGFR.

CONCLUSION

In experienced hands RAPN for renal tumours with a PADUA score of ≥10 is feasible with short WIT, acceptable major complication rate and good long-term renal functional outcomes. A slightly higher risk of PSMs can be expected due to the high surgical complexity of these lesions. The robotic technology allows a safe expansion of the indications of minimally invasive PN to anatomically very challenging renal lesions in referral centres.

Editorial: Complex tumours, partial nephrectomy and functional outcomes

In the paper by Volpe et al. [1], excellent renal functional outcomes are associated with partial nephrectomy in patients with high PADUA score cancers. The study is notable because it shows that, even in patients who are typically considered candidates for radical nephrectomy, partial nephrectomy can maintain excellent estimated GFR (eGFR) and outcomes; however, because we perform nephron-sparing procedures on patients who may also be candidates for radical nephrectomy, we must consider the varied nature of some of the data on partial nephrectomy.

The literature on renal ischaemia and functional outcomes is heterogeneous and highly debated [2]. There have been several contradictory studies and changes over time in the literature based on technology, surgeon, centre, measurement and, now, correlation with parenchyma-sparing.

A study conducted by the European Organisation for the Research and Treatment of Cancer (EORTC) compared radical nephrectomy (essentially an ischaemic time of infinity) and partial nephrectomy, reporting a 10-year overall survival benefit for patients treated with radical nephrectomy [3]. Nevertheless, this oft-criticized randomised trial also showed better eGFR in partial nephrectomy. The survival benefit reported in that study is countered by population-based studies suggesting that partial nephrectomy may still be a better option when feasible [4]. Unfortunately, these population-based studies may be considered to provide a lower level of evidence than a randomised study, and are also prone to several biases, the most notable being selection of both patients and centres. Surgeons may be more likely to perform nephron-sparing in patients in lower-risk groups. There are also other questions to consider. If a patient is more likely to be referred to a larger centre for partial nephrectomy, are they not also likely to be referred for their coronary artery bypass, aortic surgery, general medical care and even emergency care? Are these patients more likely to seek out second opinions for all of their medical care? Will this affect mortality? Are they more motivated and engaged in their own overall healthcare? These are just a few of the confounding factors that could influence outcomes and are difficult to control in population-based studies. Nevertheless, I am a firm believer in partial nephrectomy, and particularly in preserving renal function, as the better choice for the treatment of both straightforward and complex lesions. It will be difficult, however, to completely negate the implications of the EORTC trial.

Does reasonable ischaemic time affect eGFR outcome? The present study by Volpe et al. [1] would suggest that reasonable ischaemic times are completely acceptable. Several contradictory studies point out the benefits and risks of a limited or minimized clamp time for partial nephrectomy. Another separate paper by White et al. [5] is consistent with other studies that show that a clamped partial nephrectomy, even for high complexity masses, results in a minimal loss of renal function, if at all. Although there is also enthusiasm for a zero ischaemia technique, it is critical to point out that this may be surgeon-, patient-, technique- and institution-dependent. Ultimately, however, we are splitting hairs over a few points of eGFR. The real issue with long-term GFR outcomes in our patients is not only the impact of a few minutes of renal ischaemia, but also control of hypertension, diabetes and their role in medical renal disease. There is an absence of urological literature that controls for patients’ glycated haemoglobin levels or measures hypertension monthly and records the response to medical therapy. These critical pieces of information confound all eGFR and comparative measurements and make it difficult to compare published outcomes. Perhaps the best medical advice we can give patients is to diet, exercise and eat healthily for better overall health. In some sense, this advice may be far more important than the decision of partial vs radical nephrectomy for a complex mass.

What are the logical conclusions of these dilemmas? Clamped partial nephrectomy is possible in complex cases, and the procedure salvages eGFR. Further refinements are also interesting academically, including papers on parenchyma-sparing. Nevertheless, if we are serious about ‘healthy kidneys’, we might take a holistic approach and encourage our patients to pursue a healthier lifestyle so they can bolster lifelong preservation of renal function and general wellness. Would the effect be more profound than a few minutes of ischaemic time? I am betting it would.

Sam B. Bhayani 

Division of Urological Surgery, Washington University School of Medicine and Barnes-Jewish West County Hospital, St Louis, MO, USA

References

1 Volpe A, Garrou D, Amparore D et al. Perioperative and renal functional outcomes of elective robot-assisted partial nephrectomy for renal tumors with high surgical complexity. BJU Int 2014; 114: 903–9

2 Lane BR, Russo P, Uzzo RG et al. Comparison of cold and warm ischemia during partial nephrectomy in 660 solitary kidneys reveals predominant roles of nonmodifiable factors in determining ultimate renal function. J Urol 2011; 185: 421–7

3 Van Poppel H, Da Pozzo L, Albrecht W et al. A prospective, randomized EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol 2011; 59: 543–52

4 Sun M, Trinh Q-D, Bianchi M et al. A non-cancer related survival benefit is associated with partial nephrectomy. Eur Urol 2012; 61: 725–31

5 White MA, Georges-Pascal H, Autorino R et al. Outcomes of robotic partial nephrectomy for renal masses with nephrometry score of ≥ 7. Urology 2011; 77: 809–13

 

Patient with De Novo Adenosquamous Carcinoma of the Prostate

We report a case of ASC arising spontaneously in a 54 year old male with no previous risk factors.

Authors: Love, Matthew; Storey, Barckley; Alatassi, Houda; Tonkin, Jeremy
Corresponding Author: Love, Matthew

 

Abstract
Primary adenosquamous cell carcinoma of the prostate (ASC) is an exceedingly rare and aggressive form of prostate cancer, making up <1% of all diagnoses. Since its initial description by Thompson in 1942, there have been fewer than 30 cases reported in the literature. Recent reports of age-adjusted incidence rates of ASC have been shown to be around 0.03 cases per million people per year, making it less prevalent than pure squamous cell carcinoma, an exceedingly rare subtype in itself. While the majority of these tend to arise subsequent to endocrine or radiation treatment with squamous differentiation, approximately one-third of cases have arisen in a de novo setting. We report a case of ASC arising spontaneously in a 54 year old male with no previous risk factors.

Introduction
Primary adenosquamous cell carcinoma of the prostate (ASC) is an exceedingly rare and aggressive form of prostate cancer. Since its initial description by Thompson in 1942, there have been fewer than 30 cases reported in the literature [1]. While the majority of these tend to arise subsequent to endocrine or radiation treatment with squamous differentiation, approximately one-third of cases have arisen in a de novo setting [2]. We report a case of ASC arising spontaneously in a 54 year old African American male with no previous risk factors.

Case Report
A 54 year old African American male was referred to the University of Louisville Department of Urology following detection of an elevated PSA of 20 ng/mL on annual screening. He denied hematuria, dysuria, ejaculatory issues, or lower urinary tract symptoms at the time of presentation. Past medical history was noncontributory and there was no history of prostate cancer or any other malignancies in his family. On digital rectal examination the patient was noted to have a 40 gram prostate that was firm, non-tender, and with no discernible nodules. Repeat PSA was obtained and was found to be 46.7 ng/mL and he was subsequently scheduled for an ultrasound guided prostate biopsy.

Standard 12 core template prostate biopsy revealed adenosquamous carcinoma of the prostate, Gleason 4+4=8 in 7/12 cores and involving more than 50% of each core (See Figure 1 and Figure 2). As a result, an extensive metastatic workup was performed. Bone scan revealed multiple metastatic sites including the patient’s right rib, pubic symphysis, and iliac crest. CT abdomen/pelvis was obtained showing extensive retroperitoneal lymphadenopathy. Chest X-ray was negative for disease.

Due to the extensive metastatic nature of the disease, the patient opted for hormone deprivation therapy and an elective orchiectomy was performed. He was then referred to medical oncology for chemotherapeutic intervention.

Discussion/Conclusion
ASC of the prostate is among one of the rarest and most aggressive subtypes of prostate cancer making up <1% of all diagnoses [3]. Recent reports of age-adjusted incidence rates of ASC have been shown to be around 0.03 cases per million people per year, making it less prevalent than pure squamous cell carcinoma, an exceedingly rare subtype in itself [4].

The underlying mechanism for the progression and development of ASC is unknown and debated; however, most theories contend that differentiation is triggered by the various treatment modalities rather than de novo development [5]. While over two thirds of the cases of ASC originate in patients with previously diagnosed adenocarcinoma of the prostate who have been treated with additional endocrine/radiation therapy, it is extremely rare to find a primary case of this particular subtype[5]. While some believe that hormonal treatment and radiotherapy induce squamous metaplasia in the glandular cells of adenomatous prostate cancer, others contend that ASC develops de novo from divergent differentiation from epithelial stem cell lines within the prostatic cells [6] [7]. Due to the infrequent occurrence of this disease there are very few available studies to examine the mechanism behind this metaplastic process and research is currently undergoing.

ASC is defined by the presence of both glandular and squamous components on histological examination. The squamous elements of ASC constitute on average of 40% of the tumor volume but can range anywhere from 5-95% [8]. This wide range of cell types is reflected in ASC variability through immunohistochemical staining. Stains such as PSA, PSAP, and low molecular weight keratin (CAM5.3) are commonly found only in the glandular components of ASC and therefore patients with a large squamous fraction can have normal serum levels of PSA, possibly further delaying diagnosis [3]. Similarly, the squamous portion can stain positive for high molecular weight keratin (AE3), but this can vary depending on the amount of tissue that has squamous components involved (See Table 1) [9]. Additionally, glandular components have a tendency to be more high grade with an average Gleason score of >6, however, this is also a controversial point as some have suggested that Gleason scoring should not be applied to this subtype [8].

ASC tends to follow the traditional metastatic pathways similar to adenocarcinoma of the prostate, starting with local invasion and then spreading to bone and other distant soft tissue sites. However, one notable difference is that unlike standard prostatic adenocarcinoma, bone metastatic sites are characteristically osteolytic rather than osteoblastic in nature [3].

ASC is an extremely aggressive subtype of prostate cancer and in most cases is found to have widely metastasised at time of diagnosis, suggesting that this disease has a tendency to disseminate early. Most cases reported in the literature presented in individuals who were found to be in urinary retention and the pathological diagnosis was made on TURP specimens [8]. The disease is highly resistant to radiation and chemotherapy and in those individuals fortunate enough to be diagnosed early with localized/regional disease, prostatectomy shows some survival advantage [2]. It is not clear whether hormone ablation is an effective treatment modality, as some authors suggest an early response while others have noted that patients are refractory to hormone deprivation. Long term survival is extremely poor. Wang et al, evaluating SEER data and isolating for patients with an ASC diagnosis, found that the median cancer specific survival was 16 months [2]. For patients who presented with distant disease, the 6 month survival rate was only 20% with all dying within one year of diagnosis.

While literature on the subject of ASC is limited, it appears that the best initial treatment for this particular type of cancer is aggressive surgical intervention in patients with regionally restricted disease. However, due to the highly aggressive nature of this disease in most cases, such as this one, patients present with widely disseminated disease and are relegated to a regimen of hormone ablation and chemotherapy. Currently there are no recommended chemotherapeutic regimens targeted at ASC.

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Fig. 1

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Fig. 2

References
1. Thompson GJ. Transurethral resection of malignant lesions of the prostate gland. JAMA, 1942;120: 1105-9.
2. Wang J, Wang FW, LaGrange CA, et al. Clinical features and outcomes of 25 patients with primary adenosquamous cell carcinoma of the prostate. Rare Tumors, 2010; 2(3): e47.
3. Humphrey PA. Histological variants of prostatic carcinoma and their significance. Histopathology, 2012; 60(1): 59-74.
4. Marcus DM, Goodman M, Jani AB, et al. A comprehensive review of incidence and survival in patients with rare histological variants of prostate cancer in the United States from 1973 to 2008. Prostate Cancer and Prostatic Disease, 2012. doi: 10.1038/pcan.2012.4.
5. Mazzucchelli R, Lopez-Beltran A, Cheng L, et al. Rare and unusual histological variants of prostatic carcinoma: clinical significance. BJU International, 2008; 102: 1369–1374.
6. Baydar DE, Kosemehmetoglu K, Akdogan B, et al. Prostatic Adenosquamous Carcinoma Metastasizing to Testis. The Scientific World Journal, 2006; 6: 2491–2494.
7. Egilmez T, Bal N, Guvel S, et al. Adenosquamous carcinoma of the prostate. Int J Urol, 2005; 12(3): 319-21.
8. Parwani AV, Kronz JD, Genega EM, et al. Prostate carcinoma with squamous differentiation: an analysis of 33 cases. Am J Surg Pathol, 2004; 28(5): 651-7.
9. Gattuso P, Carson HJ, Candel A, et al. Adenosquamous carcinoma of the prostate. Hum Pathol, 1995; 26(1): 123-6.

 

Table 1

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Immunohistochemicalstaining patterns of adenocarcinomas and squamous cell carcinomas of the prostate.

 

Date added to bjui.org: 14/12/2012

DOI: 10.1002/BJUIw-2012-087-web

 

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