Michael Kerger

Operative Details and Oncological and Functional Outcome of Robotic-Assisted Laparoscopic Radical Prostatectomy: 400 Cases with a Minimum of 12 Months Follow-up ☆

BACKGROUND Robotic-assisted laparoscopic radical prostatectomy (RALP) using the da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA) is increasingly used for the management of localised prostate cancer. OBJECTIVE We report the operative details and short-term oncological and functional outcome of the first 400 RALPs performed at our unit. DESIGN, SETTING AND PARTICIPANTS From December 2003 to August 2006, 400 consecutive patients underwent RALP at our institution. A prospective database was established to record the relevant details of all RALP cases. SURGICAL PROCEDURE A six port transperitoneal approach using a 4-arm da Vinci system was used to perform RALP. This database was reviewed to establish the operative details and oncological and functional outcome of all patients with a minimum of 12 months follow-up. MEASUREMENTS Perioperative characteristics and outcomes are reported. Functional outcome was assessed using continence and erectile function questionnaires. Biochemical recurrence (prostate-specific antigen (PSA) > or =0.2 ng/mL) is used as a surrogate for cancer control. RESULTS AND LIMITATIONS The mean age+/-standard deviation (SD) was 60.2+/-6 years. Median PSA level was 7.0 (interquartile range (IQR) 5.3-9.6) ng/mL. The mean operating time+/-SD was 186+/-49 mins. The complication rate was 15.75% comprising Clavien grade I-II and Clavien grade III complications in 10.5% and 5.25% of patients respectively. The overall positive surgical margin rate was 19.2% with T2 and T3 positive margin rates of 9.6% and 42.3% respectively. The biochemical recurrence-free survival was 86.6% at a median follow-up of 22 (IQR=15-30) months. At 12 months follow-up, 91.4% of patients were pad-free or used a security liner. Of those men previously potent (defined as Sexual Health Inventory for Men [SHIM] score > or =21) who underwent nerve-sparing RALP, 62% were potent at 12 months. CONCLUSIONS The safety and feasibility of RALP has already been established. Our initial experience with this procedure shows promising short-term outcomes.

Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.

Robotic radical prostatectomy as the initial step in multimodal therapy for men with high-risk localised prostate cancer: initial experience of 160 men

Study Type – Therapy (case series)

Microscopic assessment of fresh prostate tumour specimens yields significantly increased rates of correctly annotated samples for downstream analysis

Aims: To assess if performing frozen sections of tissue biopsies from fresh radical prostatectomy specimens, prior to tissue banking, could improve the identification of the banked samples compared to standard fresh tumour banking procedures. Methods: Tissue biopsies banked from 332 fresh prostatectomy specimens were assessed for accuracy of diagnosis, comparing two separate methods of tumour identification: one in which tumour was identified in the gross specimen by visual inspection (n = 155) and one in which rapid frozen sectioning was applied (n = 177). The associations with correct tumour annotation and clinicopathological variables, including age, pre-operative prostate specific antigen (PSA) levels, pathological Gleason score, pathological T stage, tumour volume and surgical margins, were examined using univariable and multivariable binary logistic regression models. Results: For the gross visual inspection cohort the rate of correctly identifying and banking specimens containing prostate cancer was 69%. For the cohort assessed with rapid frozen sections, 94% of banked specimens actually had cancer. On multivariable analysis, we found that only frozen sectioning and tumour volume variables were independent predictors of correctly banked tumour specimens whilst all other routinely reported pathological variables had no influence on the success rates of fresh prostate tumour banking. Conclusion: The success rate for correctly banking fresh prostate tumour specimens is directly related to the tumour volume. Frozen section scrutiny of prostate samples is recommended to prevent misclassification of the banked material.

3D modelling of radical prostatectomy specimens: Developing a method to quantify tumor morphometry for prostate cancer risk prediction.

Prostate cancer displays a wide spectrum of clinical behaviour from biological indolence to rapidly lethal disease, but we remain unable to accurately predict an individual tumors future clinical course at an early curable stage. Beyond basic dimensions and volume calculations, tumor morphometry is an area that has received little attention, as it requires the analysis of the prostate gland and tumor foci in three-dimensions. Previous efforts to generate three-dimensional prostate models have required specialised graphics units and focused on the spatial distribution of tumors for optimisation of biopsy strategies rather than to generate novel morphometric variables such as tumor surface area. Here, we aimed to develop a method of creating three-dimensional models of a prostates pathological state post radical prostatectomy that allowed the derivation of surface areas and volumes of both prostate and tumors, to assess the methods accuracy to known clinical data, and to perform initial investigation into the utility of morphometric variables in prostate cancer prognostication. Serial histology slides from 21 prostatectomy specimens covering a range of tumor sizes and pathologies were digitised. Computer generated three-dimensional models of tumor and prostate space filling models were reconstructed from these scanned images using Rhinoceros 4.0 spatial reconstruction software. Analysis of three-dimensional modelled prostate volume correlated only moderately with weak concordance to that from the clinical data (r=0.552, θ=0.405), but tumor volume correlated well with strong concordance (r=0.949, θ=0.876). We divided the cohort of 21 patients into those with features of aggressive tumor versus those without and found that larger tumor surface area (32.7 vs 3.4cc, p=0.008) and a lower tumor surface area to volume ratio (4.7 vs 15.4, p=0.008) were associated with aggressive tumor biology.

Tracking clonal diversity in metastatic prostate cancer progression.

193 Background: Genomic heterogeneity has been observed in a number of tumor types including prostate cancer. However, how subclonal tumor diversity changes during metastasis and progression to lethality remains unexplored. Large scale genomic analyses have reported the most prevalent somatic aberrations associated with the dominant clone of the tumor without permitting an analysis of subclonal complexity or how this complexity impinges on metastatic potential or resistance to treatment. Methods: To understand and track the evolution of lethal prostate cancer from initial therapy to end stage metastases, we performed longitudinal and multiregional sampling of tumors from 7 patients with lethal prostate cancer. We performed whole-genome sequencing, RNA sequencing, and SNP profiling. Computational approaches were used to reconstruct the genetic relationships and evolution of the tumors. These evolutionary tree reconstructions allowed us to observe the dynamics of chromoplexy and mutational processes along s...