Simon Tanguay

Active Surveillance of Small Renal Masses: Progression Patterns of Early Stage Kidney Cancer ☆

BACKGROUNDnMost early stage kidney cancers are renal cell carcinomas (RCCs), and most are diagnosed incidentally by imaging as small renal masses (SRMs). Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize.nnnOBJECTIVEnTo determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology.nnnDESIGN, SETTING, AND PARTICIPANTSnA multicenter prospective phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and/or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression.nnnINTERVENTIONnPatients underwent serial imaging and needle core biopsies.nnnMEASUREMENTSnWe measured rates of change in tumor diameter (growth measured by imaging) and progression to ≥ 4 cm, doubling of tumor volume, or metastasis with histology on biopsy.nnnRESULTS AND LIMITATIONSnLocal progression occurred in 25 patients (12%), plus 2 progressed with metastases (1.1%). Of the 178 subjects with 209 SRMs, 127 with 151 SRMs had>12 mo of follow-up with two or more images, with a mean follow-up of 28 mo. Their tumor diameters increased by an average of 0.13 cm/yr. Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate. Limitations included no central review of imaging and pathology and a short follow-up.nnnCONCLUSIONSnThis is the first SRM active surveillance study to correlate growth with histology prospectively. In the first 2 yr, the rate of local progression to higher stage is low, and metastases are rare. SRMs appear to grow very slowly, even if biopsy proven to be RCC. Many patients with SRMs can therefore be initially managed conservatively with serial imaging, avoiding the morbidity of surgical or ablative treatment.

TGF-alpha as a candidate tumor antigen for renal cell carcinomas

ObjectivesPatients with renal cell carcinomas (RCC) have few treatment options, underscoring the importance of developing new approaches such as immunotherapy. However, few tumor associated antigens (TAA), which can be targeted by immunotherapy, have been identified for this type of cancer. von Hippel-Lindau clear cell RCC (VHL−/−RCC) are characterized by mutations in the VHL tumor suppressor gene. Loss of VHL function causes the overexpression of transforming growth factor (TGF)-α, leading us to hypothesize that TGF-α could be a potential TAA for immunotherapy of kidney cancer, which was evaluated in this study.Methods and resultsWe first confirmed the absent or weak expression of TGF-α in important normal tissues as well as its overexpression in 61% of renal tumors in comparison to autologous normal kidney tissues. In addition, we demonstrated the immunogenicity of TGF-α, by expanding many T cell lines specific for certain TGF-α peptides or the mature TGF-α protein, when presented by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. Interestingly, some of these TGF-α-specific T cells were polyfunctionals and secreted IFN-γ, TNF-α and IL-2.ConclusionWe have shown that TGF-α is a valid candidate TAA, which should allow the development of a targeted immunotherapy.

Prehabilitation for men undergoing radical prostatectomy: a multi-centre, pilot randomized controlled trial

BackgroundAn emerging field of research describes the role of pre operative health behaviours, known as prehabilitation. The preoperative period may be a more physically and emotionally salient time to introduce and foster chronic adherence to health behaviours, such as exercise, in patients compared to post-treatment during recovery. Moreover, physical and psychosocial improvements during the preoperative period may translate into an enhanced recovery trajectory with reduced operative complications and postoperative adverse effects. No studies have assessed prehabilitation for men with prostate cancer undergoing radical prostatectomy.Methods/DesignThis is a multi-centre, pilot randomized control trial conducted at two Canadian urban teaching hospitals. 100 men undergoing radical prostatectomy for prostate cancer with no contraindications to exercise will be recruited and randomized to the prehabiliation program or usual care. Prehabilitation participants will engage in a preoperative, individualized exercise program including pelvic floor muscle strengthening instructions and a healthy lifestyle guide for men with prostate cancer. These participants will be asked to engage in 60xa0minutes of home-based, unsupervised, moderate-intensity exercise on 3–4 days per week. Usual care participants will receive the same pelvic floor muscle strengthening instructions and healthy lifestyle guide only. We will assess the feasibility of conducting an adequately powered trial of the same design via recruitment rate, programmatic adherence/contamination, attrition, and safety. Estimates of intervention efficacy will be captured through measurements at baseline (4–8 weeks preoperatively), within 1xa0week prior to surgery, and postoperatively at 4, 12, and 26xa0weeks. Efficacy outcomes include: fatigue, quality of life, urinary incontinence, physical fitness, body composition, aerobic fitness, pain, and physical activity volume.DiscussionThe primary outcome of this study is to determine the feasibility of conducting a full-scale, randomized controlled trial of prehabilitation versus usual care and to estimate effect sizes that will inform sample size determinations for subsequent trials in this field. To our knowledge, this is the first study to examine a structured presurgical exercise program for men undergoing radical prostatectomy for prostate cancer. This trial will advance our understanding of strategies to efficiently and effectively use the preoperative period to optimize postoperative recovery.Trial registrationClinicaltrials.gov Identifier: NCT02036684)

Evaluation of RNA-binding motif protein 3 expression in urothelial carcinoma of the bladder: an immunohistochemical study

BackgroundRNA-binding motif protein 3 (RBM3), involved in cell survival, has paradoxically been linked to both oncogenesis as well as an increased survival in several cancers, including urothelial carcinoma (UCA).MethodsThe putative prognostic role of RBM3 was studied using cystectomy specimens with 152 invasive UCA with 35 matched metastases, 65 carcinomas in situ (CIS), 22 high-grade papillary UCAs (PAP), and 112 benign urothelium cases.ResultsThe H-score (HS, staining intensityu2009×u2009% of positive cells) was used for RBM3 immunoexpression. CIS showed the highest HS (meanu2009=u2009140) followed by benign urothelium (meanu2009=u200997). Metastases showed higher HS than primary invasive UCA (Pu2009≤u20090.0001), and high HS was associated with a lower pT stage (Pu2009≤u20090.0001) and a trend toward the absence of lymphovascular invasion (LVI, Pu2009=u20090.09), but not pN stage (Pu2009=u20090.35) and surgical margin status (Pu2009=u20090.81). Univariate analysis (UVA) of disease recurrence only showed an association between pN stage and LVI (Pu2009=u20090.005 and 0.03, respectively). On UVA of mortality, pT stage was strongly associated with death (Pu2009=u20090.01) while pN stage, LVI, surgical margin status, and HS were not. Multivariate analysis confirmed the lack of HS association with recurrence (Pu2009=u20090.08) and death (Pu2009=u20090.32).ConclusionsStronger RBM3 immunoexpression correlated with lower stage tumors and a diminished risk for LVI. However, RBM3 does not seem to carry a prognostic significance for clinical outcome (recurrence and mortality). The exact prognostic role of RBM3 in UCA is yet to be determined.

Canadian Men’s perspectives about active surveillance in prostate cancer: need for guidance and resources

BackgroundIn prostate cancer, men diagnosed with low risk disease may be monitored through an active surveillance. This research explored the perspectives of men with prostate cancer regarding their decision-making process for active surveillance to identify factors that influence their decision and assist health professionals in having conversations about this option.MethodsFocus group interviews (nxa0=xa07) were held in several Canadian cities with men (Nxa0=xa052) diagnosed with prostate cancer and eligible for active surveillance. The men’s viewpoints were captured regarding their understanding of active surveillance, the factors that influenced their decision, and their experience with the approach. A content and theme analysis was performed on the verbatim transcripts from the sessions.ResultsPatients described their concerns of living with their disease without intervention, but were reassured by the close monitoring under AS while avoiding harmful side effects associated with treatments. Conversations with their doctor and how AS was described were cited as key influences in their decision, in addition to availability of information on treatment options, distrust in the health system, personality, experiences and opinions of others, and personal perspectives on quality of life.ConclusionsMen require a thorough explanation on AS as a safe and valid option, as well as guidance towards supportive resources in their decision-making.

Changes in the outcome of prostate biopsies after preventive task force recommendation against prostate-specific antigen screening

BackgroundThe benefits of PSA-based screening for prostate cancer (PCa) are controversial. The Canadian and American Task Forces on Preventive Health Care (CTFPHC & USPSTF) have released recommendations against the use of routine PSA-based screening for any men. We thought to assess the impact of these recommendations on the outcomes and trends of prostate needle biopsies.MethodsA complete chart review was conducted for all men who received prostate needle biopsies at McGill University Health Center between 2010 and 2016. Of those, we included 1425 patients diagnosed with PCa for analysis. We Compared 2 groups of patients (pre and post recommendations’ release date) using Welch’s t-tests and Chi-square test. A multivariate logistic regression model was used to analyze variables predicting worse pathological outcomes.ResultsWhen the release date of the USPSTF draft (October 2011) was used as a cut-off, we found an average annual decrease of 10.6% in the total number of biopsies. The median (IQR) baseline PSA levels were higher in post-recommendations group (nu2009=u2009977) when compared to pre-recommendations group (nu2009=u2009448) [8xa0ng/ml (5.7–12.9) versus 6.4xa0ng/ml (4.9–10.1), respectively. Pu2009=u20090.0007]. Also, post-recommendations group’s patients had higher Gleason score (G7: 35.4% versus 28.4% and G8-G10: 31.2% versus 18.1%, respectively. Pu2009<u20090.0001). Moreover, they had higher intermediate and high-risk PCa classification (36.4% versus 32.8% and 35.5% versus 22.1%, respectively. Pu2009<u20090.0001). The recommendations release date was an independent variable associated with higher Gleason score in prostate biopsies (OR: 2.006, 95%CI: 1.477–2.725). Using the CTFPHC recommendations release date (October 2014) as a cut-off in further analysis, revealed similar results.ConclusionsOur results revealed a reduction in the number of prostate needle biopsies performed over time after the recommendations of the preventive task forces. Furthermore, it showed a significant relative increase in the higher risk PCa diagnosis. The oncological outcomes associated with this trend need to be examined in further studies.

Describing perspectives of health care professionals on active surveillance for the management of prostate cancer

BackgroundOver the last decade, active surveillance has proven to be a safe approach for patients with low-risk prostate cancer. Although active surveillance presents several advantages for both patients and the health care system, all eligible patients do not adopt this approach. Our goal was to evaluate the factors that influence physicians to recommend active surveillance and the barriers that impact adherence to this approach.MethodsFocus groups (nu2009=u20095) were held with physicians who provided care for men with low-risk prostate cancer and had engaged in conversations with men and their families about active surveillance. The experience of health care professionals (HCPs) was captured to understand their decisions in proposing active surveillance and to reveal the barriers and facilitators that affect the adherence to this approach. A content analysis was performed on the verbatim transcripts from the sessions.ResultsAlthough physicians agreed that active surveillance is a suitable approach for low-risk prostate cancer patients, they were concerned about the rapidly evolving and non-standardized guidelines for patient follow-up. They pointed out the need for additional tools to appropriately identify proper patients for whom active surveillance is the best option. Urologists and radiation-oncologists were keen to collaborate with each other, but the role of general practitioner remained controversial once patients were referred to a specialist.ConclusionsIntegration of more reliable tools and/or markers in addition to more specific guidelines for patient follow-up would increase the confidence of both patients and physicians in the choice of active surveillance.