Richard P. Meijer

Prostate Sparing Cystectomy for Bladder Cancer: 20-Year Single Center Experience

PURPOSE We evaluated long-term oncologic and functional results after prostate sparing cystectomy for bladder cancer. MATERIALS AND METHODS A total of 120 patients with cT1-4N0-3 bladder cancer were treated with prostate sparing cystectomy between 1994 and 2013, of whom 110 had a followup of 2 years or greater and were eligible for analysis. To rule out tumor in the bladder neck, prostatic urethra or prostate cancer all patients underwent preoperative transurethral biopsy of the bladder neck and prostatic urethra, prostate specific antigen measurement and transrectal ultrasound with biopsies. We assessed oncologic outcomes (disease specific and recurrence-free survival), recurrence rates, prostate cancer and functional results (continence, voiding, and erectile and ejaculatory function). RESULTS Mean patient ± SD age was 56.2 ± 8.3 years and median followup was 77.0 months (IQR 57-116). Two and 5-year disease specific survival rates were 76.2% and 66.5%, 2 and 5-year recurrence-free survival rates were 71.2% and 66.6%, and distant and local recurrence rates were 34.2% and 10.0%, respectively. One local recurrence was in the remnant prostatic urothelium. Prostate cancer was diagnosed in 2.7% of cases. Complete daytime and nighttime continence was achieved in 96.2% and 81.9% of patients, and erectile function and antegrade ejaculation were intact in 89.7% and 35.5%, respectively. CONCLUSIONS Our long-term data show that prostate sparing cystectomy is an oncologically safe procedure with excellent functional results in a subset of carefully selected patients with bladder cancer without evidence of urothelial carcinoma in the prostatic urethra/bladder neck and no prostate cancer.

Occult lymph node metastases in patients with carcinoma invading bladder muscle: incidence after neoadjuvant chemotherapy and cystectomy vs after cystectomy alone.

To investigate the effect of neoadjuvant chemotherapy (NAC) on the incidence of lymph node (LN) metastases in clinically node‐negative (cN0) patients with carcinoma invading the bladder muscle (MIBC).

Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder

To assess the long‐term outcome and the risk for local recurrence of patients with small cell carcinoma of the bladder (SCCB) treated with neoadjuvant chemotherapy followed by external beam radiotherapy (sequential chemoradiation).

Response to induction chemotherapy and surgery in non-organ confined bladder cancer: A single institution experience

AIM To evaluate the outcome of patients with locally advanced muscle-invasive and/or lymph node positive bladder cancer treated with induction chemotherapy and additional surgery. METHODS All patients who were treated with induction chemotherapy in our institution between 1990 and 2010, were retrospectively evaluated using an institutional database. Induction chemotherapy consisted of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC), or a combination of gemcitabine with either cisplatin or carboplatin (GC). RESULTS In total 152 patients were identified, with a mean age of 59 years (range 31-76). One hundred and seven patients (70.4%) received MVAC, 35 patients received GC (23.0%) and 10 patients received GC after initial treatment with MVAC (6.6%). Median follow-up was 68 months (range 4-187 months). Overall 125 patients (82.2%) underwent cystectomy, whereas 12 patients (7.9%) received radiotherapy. Fifteen patients had no local treatment. Median overall survival was 18 months (95%CI 15-23 months). In 37.5% of patients with complete clinical response, residual disease was found at surgery (positive predictive value, PPV 62.5%). Complete pathological response was seen in 26.3% of patients, with a 5 year overall survival (OS) estimate of 54% (39%-74%). For patients with persisting node positive disease after induction chemotherapy and surgery OS was significantly worse (p < 0.0001). CONCLUSIONS Complete clinical and/or pathological response to induction chemotherapy results in a significant survival benefit. The accuracy of the current clinical response evaluation after induction chemotherapy is limited. Although surgery may be important for staging and prognostic purposes, its role is unclear in node positive disease after induction chemotherapy.

The risk profiles of three clinical types of carcinoma in situ of the bladder

Study Type – Therapy (individual cohort)

Lymph node count at radical cystectomy does not influence long-term survival if surgeons adhere to a standardized template

INTRODUCTION Multiple bladder cancer studies report that the number of removed lymph nodes (lymph node count [LNC]) at radical cystectomy (RC) is positively associated with survival. Although these reports suggest that LNC can be used as a proxy for surgical quality, all studies used variable or inconsistent pelvic lymph node dissection (PLND) templates. We therefore wished to establish whether LNC at RC influences survival if surgeons adhere to a standardized PLND template. MATERIALS AND METHODS We included 274 patients who underwent RC from January 2005 until December 2012. All RCs were performed in either one of 2 hospitals (hospital A or B) by the same 4 urologists (all from hospital A) and a standardized PLND template was applied. PLND specimens were processed by 2 independent pathology departments (hospital A and B). We used Cox regression analysis to investigate the prognostic value of LNC adjusted for patient characteristics. We also compared LNC between hospitals and surgeons and investigated the effect of both the variables on overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). RESULTS Median LNC was 17 (interquartile range = 12). At a median follow-up of 64.3 months, there was no association between LNC and OS (P = 0.328), CSS (P = 0.645), or DFS (P = 0.450). Median LNC was higher in hospital B than in hospital A (20.0 vs. 16.0, P = 0.003). Median LNC varied significantly among surgeons (12-20, P<0.001). Neither the hospital of surgery nor the surgeon performing PLND influenced OS (P = 0.771 and P = 0.982, respectively), CSS (P = 0.310 and P = 0.691, respectively), or DFS (P = 0.256 and P = 0.296, respectively). CONCLUSION If surgeons adhere to a standardized template, LNC at RC does not affect long-term survival.

Long-term Outcomes of Follow-up for Initially Localised Clear Cell Renal Cell Carcinoma: RECUR Database Analysis

BACKGROUND Optimal follow-up (FU) strategy to detect potentially curable (PC) recurrences after treatment of localised clear cell renal cell carcinoma (ccRCC) is unclear. This study retrospectively analysed a large international database to determine recurrence patterns and overall survival (OS), as part of a wider project to issue recommendations on FU protocols. OBJECTIVE To analyse associations between RCC recurrences in patients with ccRCC, their risk group stratifications, treatments, and subsequent outcomes. DESIGN, SETTING, AND PARTICIPANTS Nonmetastatic ccRCC patients treated with curative intent between 1 January 2006 and 31 December 2011, with at least 4 yr of FU, were included. Patient, tumour and recurrence characteristics, Leibovich score, and management and survival data were recorded. Isolated local, solitary, and oligometastatic (three or fewer lesions at a single site) recurrences were considered PC, while all others were probably incurable (PI). INTERVENTION Primarily curative surgical treatment of ccRCC while at recurrence detection metastasectomy, systemic therapy, best supportive care, or observation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Incidence, time to recurrence (TTR), and OS were measured. Competing risk analysis, Kaplan-Meier, and Cox regression models were used. RESULTS AND LIMITATION Of 1265 patients with ccRCC, 286 had a recurrence, with 131 being PC and 155 PI. Five-year cumulative risks of recurrence for low- (n=53), intermediate- (n=105), and high-risk (n=128) patients were, respectively, 7.2%, 23.2%, and 61.6%, of whom 52.8%, 37.1%, and 30.5% were PC, respectively. Median TTR was 25.0 for PC patients versus 17.3 mo for PI patients (p=0.004). Median OS was longer in PC compared with that in PI patients (p<0.001). Competing risk analysis showed highest risk of ccRCC-related death in younger and high-risk patients. Limitations were no data on comorbidities, retrospective cohort, and insufficient data excluding 12% of cohort. CONCLUSIONS Low-risk group recurrences are rare and develop later. Treatment of recurrences with curative intent is disappointing, especially in high-risk patients. An age- and risk score-dependent FU approach is suggested. PATIENT SUMMARY We analysed data from eight European countries, and found that the incidence of the kidney cancer recurrence and patient survival correlated with clinical factors known to predict cancer recurrence reliably and age. We conclude that these factors should be used to design follow-up strategies.

Focal MRI-Guided Salvage High-Dose-Rate Brachytherapy in Patients With Radiorecurrent Prostate Cancer

Introduction: Whole-gland salvage treatment of radiorecurrent prostate cancer has a high rate of severe toxicity. The standard of care in case of a biochemical recurrence is androgen deprivation treatment, which is associated with morbidity and negative effects on quality of life. A salvage treatment with acceptable toxicity might postpone the start of androgen deprivation treatment, might have a positive influence on the patients’ quality of life, and might even be curative. Here, toxicity and biochemical outcome are described after magnetic resonance imaging–guided focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer. Materials and Methods: Seventeen patients with pathologically proven locally recurrent prostate cancer were treated with focal high-dose-rate brachytherapy in a single 19-Gy fraction using magnetic resonance imaging for treatment guidance. Primary radiotherapy consisted of external beam radiotherapy or low-dose-rate brachytherapy. Tumors were delineated with Ga-68–prostate-specific membrane antigen or F18-choline positron emission tomography in combination with multiparametric magnetic resonance imaging. All patients had a prostate-specific antigen level of less than 10 ng/mL at the time of recurrence and a prostate-specific antigen doubling time of ≥12 months. Toxicity was measured by using the Common Terminology Criteria for Adverse Events version 4. Results: Eight of 17 patients had follow-up interval of at least 1 year. At a median follow-up interval of 10 months (range 3-40 months), 1 patient experienced a biochemical recurrence according to the Phoenix criteria, and prostate-specific membrane antigen testing revealed that this was due to a distant nodal metastasis. One patient had a grade 3 urethral stricture at 2 years after treatment. Conclusion: Focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer showed grade 3 toxicity in 1 of 17 patients and a distant nodal metastasis in another patient. Whether this treatment option leads to cure in a subset of patients or whether it can successfully postpone androgen deprivation treatment needs further investigation.

Second salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer

Purpose Salvage treatments for localized radiorecurrent prostate cancer can be performed safely when a focal and image guided approach is used. Due to the low toxicity, the opportunity exists to investigate a second salvage treatment when a second locally recurrent prostate cancer occurs. Here, we describe a second salvage treatment procedure of 4 patients. Material and methods Four patients with a pathologically proven second local recurrence were treated in an outpatient magnetic resonance imaging (MRI)-guided setting with a single fraction of 19 Gy focal high-dose-rate brachytherapy (HDR-BT). Delineation was performed using choline-PET-CT or a 68Ga-PSMA PET in combination with multiparametric 3 Tesla MRI in all four patients. Toxicity was measured using common toxicity criteria for adverse events (CTCAE) version 4.0. Results With a median follow-up of 12 months (range, 6-15), there were 2 patients with biochemical recurrence as defined by the Phoenix-definition. There were no patients with grade 3 or more toxicity. In all second salvage HDR-BT treatments, the constraints for rectum, bladder, and urethra were met. Median treatment volume (GTV) was 4.8 cc (range, 1.9-6.6 cc). A median of 8 catheters (range, 6-9) were used, and the median dose to the treatment volume (GTV) was a D95: 19.3 Gy (SD 15.5-19.4 Gy). Conclusions Second focal salvage MRI-guided HDR-BT for a select group of patients with a second locally recurrent prostate cancer is feasible. There was no grade 3 or more acute toxicity for these four patients.

MRI guided focal HDR brachytherapy for localized prostate cancer: Toxicity, biochemical outcome and quality of life

PURPOSE To describe toxicity, biochemical outcome and quality of life after MRI guided focal high dose rate brachytherapy (HDR-BT) in a single fraction of 19 Gy for localized prostate cancer. MATERIALS AND METHODS Between May 2013 and April 2016, 30 patients were treated by MRI-guided focal HDR-BT. Patients with visible tumour on MRI were included. All patients were ≥65 years, T-stage <T3, Gleason ≤7, PSA <10 ng/mL and IPSS <15. Focal irradiation was delivered in a single fraction of 19 Gy to the D95 of the clinical target volume. Toxicity was reported using the Common Terminology Criteria for Adverse Events version 4. Biochemical failure was defined according to the Phoenix criteria and quality of life was measured using validated questionnaires. RESULTS Median follow up was 24 months. One patient developed a grade 2 and 3 GU toxicity after treatment. In the other 29 patients, no grade 2 or higher perioperative complications occurred. Five patients developed a biochemical recurrence. For all measured time points, there was no statistically significant deterioration in quality of life. CONCLUSION Focal MRI guided HDR-BT confers low toxicity rates and maintains quality of life. Biochemical recurrence is rather high, 5 patients developed a biochemical recurrence according to the Phoenix definition. Longer evaluation of these patients is necessary and caution is warranted before implementing focal HDR-BT in patients with localized prostate cancer.