A study into the association between local recurrence rates and surgical resection margins in organ-sparing surgery for penile squamous cell cancer.

OBJECTIVE: To evaluate the significance of close surgical margins in organ-sparing surgery (OSS) in the treatment of penile squamous cell carcinoma (pSCC) and clinicopathological factors that may influence local recurrence. PATIENTS AND METHODS: At our tertiary referral centre, between March 2001 and September 2012, 332 patients treated with OSS for pSCC had clear surgical margins. As the focus was the impact of close clear margins on local recurrence, patients with positive margins were excluded for the purpose of this study. Our overall positive margin rate for OSS in penile cancer is 7.6% (42 patients). Analysis was carried out on an on-going prospective database, including prospective accurate pathological recording of surgical margins. Patients underwent OSS after multidisciplinary team (MDT) discussion. Local recurrence was the primary outcome measured and Fisher's exact test and time-to-recurrence curves were used in the analysis. All local recurrences were scrutinised by the MDT and were categorised into: true recurrences or metachronous new occurrences (i.e. tumours arising from a background of penile intraepithelial neoplasia and forming on an epithelial surface not related to the site of initial resection). A multivariate analysis was also conducted to elucidate other factors influencing local recurrence. RESULTS: In all, 64% of the patients had a <5 mm clear deep surgical margin, with 16% clear by <1 mm. Overall, 4% of patients had a true local recurrence, with a median time to recurrence of 6 months. In all, 53% were due to embolic spread, with residual occult local disease accounting for 47%. There was a statistically significant relationship between cavernosal involvement (P = 0.014) and lymphovascular invasion (LVI; P = 0.001) and local recurrence. Although multivariate analysis revealed that the extent of clear margin was not a predictor of disease (P = 0.405), we found an increased risk of local recurrence in the clear margin cohort of <1 mm compared to those of >1 mm (P < 0.001). Those patients considered to have metachronous tumours were scrutinised by our MDT, and eight patients (2.4%) were found to have new occurrences. Our overall proportion of patients therefore needing further treatment for either new occurrences or recurrent disease after OSS stands at 6.4%. CONCLUSIONS: Overall the presence of local recurrent disease in OSS in our experience is low (4%). We report an embolic mechanism of local recurrence, strongly suggested by the presence of cavernosal involvement and LVI. We conclude that a deep clear margin of >1 mm has a very low risk of local recurrence in penile OSS.

Predictive Factors for Time to Progression after Hyperthermic Mitomycin C Treatment for High-Risk Non-Muscle Invasive Urothelial Carcinoma of the Bladder: An Observational Cohort Study of 97 Patients.

INTRODUCTION: Hyperthermic mitomycin (HM) is a novel treatment modality for selected patients with high-risk non-muscle invasive bladder cancer (NMIBC). We sought to determine predictors of response to this therapy. PATIENTS AND METHODS: A longitudinal, cohort study of 97 patients with high-risk NMIBC treated with ≥4 HM instillations on a prophylactic schedule was conducted. The primary outcome was time-to-progression survival; secondary outcomes were overall survival, cancer-specific survival, and adverse events. Descriptive statistics, Kaplan-Meier survival analyses, Cox proportional hazards modelling, and univariate and multivariable regression were performed. RESULTS: The presence of initial complete response (CR; no evidence of disease at first check video-cystoscopy and urine cytology) post-HM treatment was an independent predictor of good response to HM. Female patients and those without carcinoma in situ (CIS) also appeared to respond better to the intervention. The overall bladder preservation rate at a median of 27 months was 81.4%; 17/97 (17.5%) patients died during the course of the study. CONCLUSIONS: High-risk NMIBC patients can be safely treated with HM and have good oncological outcome. However, those without an initial CR have a poor prognosis and should be counselled towards adopting other treatment methodologies such as cystectomy. Female gender and lack of CIS may be good prognostic indicators for response to HM.

Psychosocial Impact of Penile Cancer: An Unmet Need.

Penile cancer is a rare cancer, where patients not only need to deal with the anxiety around a cancer diagnosis, but also manage the consequences of treatment on their self-esteem, body image, and intimate relationships. Many find it embarrassing and difficult to talk to family and friends. Due to this, changes in urination and other physical effects of treatment, many will withdraw from social activities too. Patients need psychosocial support and more needs to be done to address this unmet need. Holistic and multidisciplinary approaches in clinic, with access to counseling, may help patients adjust to their new situation.

Future prospects: who is the patient who still dies of prostate cancer following local treatment of high-risk prostate cancer? Can we prolong their lives using modern treatment approaches?

PURPOSE OF REVIEW: Prostate cancer remains the commonest nondermatological cause of cancer in Western men and the second leading cause of cancer death in these men. While low and intermediate-risk prostate cancers make up the vast bulk of prostate cancer diagnoses, it is high-risk prostate cancer that is a much larger killer. Management paradigms for such disease are changing and thus we review the current state of play with the management of these cancers and what the future might hold. RECENT FINDINGS: High-risk prostate cancer is a heterogeneous beast, with huge variations in disease severity. Hence, management of these cases must be tailored based on specific risk factors of individual patients, and the role for surgery especially in the lower end of the spectrum is increasing. SUMMARY: The increasing use of radical extirpative surgery might negatively impact functional outcomes but are likely to prolong lives of high-risk prostate cancer sufferers, though more research from well conducted randomized controlled trials is needed to exactly define which patient subpopulations should receive which therapies, in which orders, and at what times.

The role of transperineal template prostate biopsies in restaging men with prostate cancer managed by active surveillance.

OBJECTIVE: To evaluate the role of transperineal template prostate biopsies in men on active surveillance. PATIENTS AND METHODS: In all, 101 men on active surveillance for prostate cancer underwent restaging transperineal template prostate biopsies at a single centre. Criteria for active surveillance were ≤75 years, Gleason ≤3+3, prostate-specific antigen (PSA) ≤15 ng/mL, clinical stage T1-2a and ≤50% ultrasound-guided transrectal biopsy cores positive for cancer with ≤10 mm of disease in a single core. The number of men with an increase in disease volume or Gleason grade on transperineal template biopsy and the number of men who later underwent radical treatment were assessed. The role of PSA and PSA kinetics were studied. RESULTS: In all, 34% of men had more significant prostate cancer on restaging transperineal template biopsies compared with their transrectal biopsies. Of these men, 44% had disease predominantly in the anterior part of the gland, an area often under-sampled by transrectal biopsies. In the group of men who had their restaging transperineal template biopsies within 6 months of commencing active surveillance 38% had more significant disease. There was no correlation with PSA velocity or PSA doubling time. In total, 33% of men stopped active surveillance and had radical treatment. CONCLUSIONS: Around one-third of men had more significant prostate cancer on transperineal template biopsies. This probably reflects under-sampling by initial transrectal biopsies rather than disease progression.

Practice Patterns Among Penile Cancer Surgeons Performing Dynamic Sentinel Lymph Node Biopsy and Radical Inguinal Lymph Node Dissection in Men with Penile Cancer: A eUROGEN Survey.

Dynamic sentinel lymph node biopsy (DSNB) and radical inguinal lymph node dissection (ILND) are important in the management of penile cancer patients, but high-level evidence for preoperative, perioperative, and postoperative management remains scarce. According to an online survey of 35 surgeons from ten European countries, 57% perform >10 ILND procedures per year and 86% offer DSNB. Furthermore, management differs substantially for dye injection site, use of lymphoscintigraphy, preferred incision sites, techniques for lymphatic control, duration of empiric antibiotic therapy, perioperative thromboprophylaxis, time points for drain removal, and definition of the ILND dissection floor. Consensus was observed for the use of perioperative antibiotics (although not duration and type) and the borders for ILND template definitions. We conclude that there is significant variation in patient management among eUROGEN penile cancer surgeons. This heterogeneity may confound multicentre studies; therefore, a consensus to standardise inguinal node management in penile cancer across European penile cancer centres is warranted. PATIENT SUMMARY: Our survey reveals that preferences and surgical techniques for inguinal lymph node sampling and removal varies significantly between European penile cancer surgeons. Consensus is needed to standardise the management approach for penile cancer.

Cystectomy outcomes in patients who have failed Radiofrequency-induced Thermo-chemotherapeutic Effect Mitomycin-C (RITE-MMC) treatment for high-risk non-muscle invasive bladder cancer (HRNMIBC)-Does it complicate surgery and adversely impact oncological outcome?

INTRODUCTION: The standard intravesical treatment for high risk non muscle invasive bladder cancer (HRNMIBC) is Bacillus Calmette-Guérin (BCG), with failure often resulting in cystectomy. Radiofrequency-Induced Thermo-chemotherapeutic Effect Mitomycin (RITE-MMC) can be an alternative in BCG failure. There has been concern that RITE-MMC may delay an inevitable cystectomy, make it more technically challenging and worsen prognosis. The aim of this study was to assess operative challenges and oncological outcome in patients undergoing cystectomy for HRNMIBC who received RITE-MMC, and contrast them with those that did not. PATIENTS AND METHODS: A retrospective study of a prospective cystectomy database was conducted. Patients treated from April 2011 to June 2017 were looked at. Inclusion criteria were HRNMIBC with BCG failure undergoing cystectomy. Patient demographics and tumour characteristics were analysed. Intraoperative blood loss and length of stay were used as surrogate markers for intra-operative difficulty. Kaplan-Meier curves were constructed to analyse all-cause mortality, cancer specific mortality and time to recurrence between the RITE-MMC treatment group and those that did not receive RITE-MMC. A multivariate analysis was conducted to assess factors that may influence readmission. RESULTS: Thirty-six patients who received RITE-MMC underwent cystectomy, compared to 102 that did not. Median ages were comparable at 72 and 69 years, respectively. Patients were followed up for a median of 24 months across the 2 groups. The commonest histological stage in both groups was CIS. There were no significant differences in intraoperative blood loss, length of stay and 90-day readmission between the 2 groups. There were proportionally fewer recurrences in the RITE-MMC group (16% vs. 19%) and median time to recurrence was longer in the RITE-MMC group (37 months vs. 24 months). Multivariate analysis did not reveal a significant correlation between pre-op RITE-MMC and post-operative readmission (P = 0.606). Survival curves show no significant difference in time to recurrence across both groups (P = 0.513), and no overall (P = 0.069) or cancer specific mortality (P = 0.129) dis-advantage was noted in the RITE-MMC group. CONCLUSION: We have found that RITE-MMC treatment does not result in a technically more challenging cystectomy and does not compromise oncological outcome compared to those patients undergoing cystectomy immediately post-BCG failure. We feel RITE-MMC remains a useful tool in a carefully selected group of patients who may not be willing to accept the morbidity of a cystectomy at the time, without significantly compromising their long-term outcome.